Many approaches have been developed over time to counter the bioavailability limitations of poorly soluble drugs. With advances in nanotechnology in recent decades, science and industry have been approaching this issue through the formulation of drugs as nanocrystals, which consist of pure drugs and a minimum of surface active agents required for stabilization. They are carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range, typically between 10 and 800 nm. By reducing particle size to nanoscale, the particle surface area available for the molecule dissolution in the direction of dissolution medium is increased, and thus bioavailability is enhanced. This approach has proven successful, as demonstrated by the number of such drug products on the market. R&D and industry have offered many technological solutions to reduce the particle size to nanoscale, and also devised solutions for the handling of particle of nanodimensions, such as methods to accurately measure nanoparticle size and techniques to prevent physicochemical and stability related problems, such as aggregation. The present work provides an overview of the more recent achievements in improving the bioavailability of poorly soluble drugs according to their administration route, and describes the methods developed to overcome physicochemical and stability related problems.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble Olaparib. Through the solubility test of Olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients for use in SMEDDS manufacturing were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. Various physicochemical properties of microemulsion incorporating Olaparib were confirmed by investigating the particle morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and oral absorption of Olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul MCM EP/NF 10%, Labrasol 80% and PEG 400 10%. Fabricated nano-sized microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that it was maintained well without any problems of either physical or chemical stability. The 5 min initial dissolution of Olaparib in fabricated formulations was improved by 10.6 times (pH1.2), 14.8 times (pH6.8) and 14.8 times (distilled water) compared to the values of Olaparib powder. The dissolution at 120min was 45.4±4.0%(pH1.2), 53.5±1.1% (pH6.8) and 58.1±1.00% (distilled water) in Olaparib powder but has been significantly improved by 1.7 times (74.8±1.9%), 1.6 times (84.2±0.3%) and 1.5 times (81.2±0.7%) in SMEDDS. Associated with the high dissolutions of Olaparib in fabricated microemulsions, the pharmacokinetic parameters were also greatly improved. The Cmax and AUCinf of Olaparib in the prepared microemulsion were increased 4.2- and 3.2-fold, respectively, compared to powder. Taken together with the results mentioned above, the microemulsion system could be an effective tool as an oral delivery formulation for Olaparib. Additionally, our results demonstrate that the SMEDDS systems comprising Capmul MCM, Labrasol and PEG 400 could be a useful option for improvement of several other poorly water-soluble drugs with physico-chemical properties similar to Olaparib.

The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.

Lignin is insoluble in water, limiting its use in the synthesis of adhesives. Therefore, in order to increase the amount of lignin raw materials used in the synthesis of adhesives, a kind of aminated lignin compounds was prepared through lignin amination reaction, and conducting structural analysis in this paper. The particle size of the amino lignin is about 100 nm, with the weight average molecular weight of 57,627 g/mol and a water solubility of 0.45g/100ml. The reaction mechanisms were proposed that the phenolic hydroxyl groups of lignin react with ammonia molecules, and thereby successfully introducing amino groups to generate the aminated lignin compounds. Therefore, this article enriches the scientific theory of lignin reactions and provides reference for the widespread application of lignin raw materials in the field of adhesives.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

China’s greenhouse industry has thousands of years of development history, although the development of modern greenhouses has come late. After decades of development of China, its greenhouse industry is in the forefront of the world. China’s greenhouse industry is experiencing rapid development, transformation and upgrading. China ranks first in the world in terms of greenhouse area, used mainly for vegetable cultivation and plays an important role in the utilization of agricultural resources and food production. In 2023, the cumulative area of new greenhouses nationwide was 1835.87 million ha. In this paper we present the latest developments in the greenhouse sector. More specifically, we present a greenhouse market development overview, the greenhouse production, the greenhouse industry, and technology development. Current problems are underpinned, development opportunities and prospects are analyzed, and measures and specific proposals are detailed for the technological development of the greenhouse sector both for increasing product quantity and quality.

Water-soluble nonionic surfactant, pentaethylene glycol monododecyl ether, C12E5, spontaneously blooms to the surface of spin-cast hydrophobic polyiso-prenes, generating hydrophilic surfaces. This system represents a simple model for hydrophilic chemical modification of rubbery polymers yet demonstrates surprisingly rich, complex and unexpected behaviour. The ver-tical depth profiles were quantified using neutron reflectometry (NR) and deuterated surfactant, and the surface properties were characterized using con-tact angle analysis and atomic force microscopy (AFM). Despite the low surface tension of the toluene solvent used in film preparation and the low surface en-ergy of the PI matrix, NR depth profiles revealed clear evidence of surfactant segregation. This surface layer was typically thicker than a monolayer, but incomplete, yet was remarkably stable with respect to dissolution, even when exposed to hundreds of thousands of times the volume of water required to dissolve all the surfactant on the surface. Despite the apparent resistance to removal from the surface, water exposure does alter the subsequent wettabil-ity of the surface, with a hydrophilic-to-hydrophobic transition occurring after rinsing. Complementary AFM images of these C12E5 / cis-PI films showed unexpected strand-like features on the surface of the film, which we attribute to a non-uniform lateral distribution of some of the surfactant. This surface structure becomes more evident after rinsing, and it appears that there are two distinct populations of surfactant on the PI film surface. We conclude that some of the bloomed surfactant exists as layers, which are relatively inert with respect to rinsing or surface modification, and some is laterally inhomogene-ous. This latter population is primarily responsible for surface wetting be-havior, but is not detected by specular NR.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer-small molecule drug combinations for which stability data is available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in-silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

In the process of sewage coagulation treatment, quartz sand is often used as a heavy medium to accelerate the settling rate of flocs, but it will adversely affect the removal efficiency of pollutants. The factors that affect the coagulation effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc, their reasonable setting is critical to. This paper was to study the optimal conditions of quartz sand enhanced coagulation(QSEC), first, single-factor tests were conducted to preliminarily explore the optimal range of influencing factors, and then response surface methodology（RSM）tests were performed to accurately determine the optimums of significant factors. The results showed that the addition of quartz sand can’t improve the water quality of coagulation treatment, but it can significantly accelerate the coagulation settlement process, the quartz sand dosage, the coagulant dosage and sewage pH all impacted significantly on its coagulation effect, and existed inflection points. A model that could guide QSEC was obtained by RSM tests. The model optimization and experimental validation showed that the optimal QSEC conditions for treating domestic sewage were as follows: the polyaluminum chloride(PAC) dosage, cationic polyacrylamide(CPAM) dosage, the sewage pH, quartz sand dosage, stirring time and settling time were 0.97 g·L-1, 2.25 mg·L-1, 7.22, 2 g·L-1, 5 minutes and 30 minutes, respectively, and the turbidity of treated sewage was reduced to 1.15 NTU.

The purpose of the present study was to evaluate the antioxidant activity and peptide levels of Feta cheese and other brined cheeses, and Metsovone cheese, and other smoked cheeses. The antioxidant activity was determined by Folin and FRAP assays, while the peptide content was determined by Bradford and Lowry assays. The assays were applied in the water soluble extract of cheeses. The results showed that Feta cheese and brined cow cheese differ in antioxidant activity. Feta cheese and brined goat cheese also differ in both antioxidant activity and peptide levels. Results also showed that Metsovone cheese and other smoked cheeses exhibit antioxidant activity and significant peptide levels. Moreover, the water soluble extracts of all cheeses show some anti-inflammatory activity, suggesting that may peptides exhibit anti-inflammatory activity.

The majority of existing numerical simulations of the effect of bridge piers on water movement are based on a limited number of bridge piers at a laboratory scale. Furthermore, some 2D numerical simulations for actual bridge projects have deficiencies, including the use of overly large mesh sizes and an inadequate treatment of bridge piers. In this study, we compare three methods of structural mesh encryption, suspension mesh, and nonstructural mesh based on Delft3D, and apply the optimization scheme to a real bridge project. It is demonstrated that optimal results can be achieved by utilising a grid size comparable to the pier diameter (Dp) in the region away from the piers. In the vicinity of the piers, the grid cell size should be no larger than 1/9 Dp. The suspended grid technique (DD Boundary) can yield results consistent with those obtained using a full-area high-resolution grid, provided that the total number of grids can be reduced and the computational time is considerably reduced. In this study, the unstructured mesh (Deflt3D Flexible Mesh) scheme was unable to capture the oscillations of the wake flow behind the bridge piers. However, the application of the optimized scheme in bridge engineering has demonstrated its practical value. The findings of this study on mesh resolution and suspension mesh scheme can be applied to the Delft3D software and are also useful for other numerical simulation work.

Plain lakes play a crucial role in the hydrological cycle of a watershed, but their interactions with adjacent rivers and downstream water bodies can create complex river-lake relationships, often leading to frequent flooding disasters. Taking Poyang Lake as an example, this paper delves into its interaction with the Yangtze River, revealing the spatiotemporal patterns of flood propagation within the lake and its impact on surrounding flood control measures. The aim is to provide insights for flood management in similar environments worldwide. This study employs a comprehensive approach combining hydrological statistical analysis and two-dimensional hydrodynamic modeling, based on extensive hydrological, topographic, and socio-economic data. The results indicate that the annual maximum outflow from Poyang Lake is primarily controlled by floods within the watershed, while the highest annual lake water level is predominantly influenced by floods from the Yangtze River. The peak discharge typically reaches the lake outlet within 48 hours, with the peak water level taking slightly longer at 54 hours. However, water storage in the lake can shorten the time for the peak discharge to arrive. When converging with floods from the Yangtze River, the peak water level may be delayed by up to 10 days due to the top-supporting interaction. Furthermore, floods from the "Five Rivers" propagate differently within the lake, affecting various lake regions to differing degrees. Notably, floods from the Fu River cause the most significant rise in lake water level under the same flow rate. The top-supporting effect from the Yangtze River also significantly impacts the water surface slope of Poyang Lake. When the Yangtze River flood discharge far exceeds that of the "Five Rivers" (i.e., when the top-supporting intensity f value exceeds 4), the lake surface becomes as flat as a reservoir. During major floods in the watershed, the water level difference in the lake can increase dramatically, potentially creating a "dynamic storage capacity" of up to 840 million cubic meters.

Climate change is a global issue that draws widespread attention from the international society. As an important component of the climate system, the water cycle is directly affected by climate change. Thus, it is very important to study the influences of climate change on the basin water cycle with respect to maintenance of healthy rivers, sustainable use of water resources, and sustainable socioeconomic development in the basin. In this study, by assessing the suitability of multiple General Circulation Models (GCMs) recommended by the Intergovernmental Panel on Climate Change, Statistical Downscaling Model (SDSM) and Automated Statistical Downscaling model (ASD) were used to generate future climate change scenarios. These were then used to drive distributed hydrologic models (Variable Infiltration Capacity, Soil and Water Assessment Tool) for hydrological simulation of the Yangtze River and Yellow River basins, thereby quantifying the effects of climate change on the basin water cycle. The results showed that suitability assessment adopted in this study could effectively reduce the uncertainty of GCMs, and that statistical downscaling was able to greatly improve precipitation and temperature outputs in global climate mode. Compared to a baseline period (1961–1990), projected future periods (2046–2065 and 2081–2100) had a slightly decreasing tendency of runoff in the lower reaches of the Yangtze River basin. In particular, a significant increase in runoff was observed during flood seasons in the southeast part. However, runoff of the upper Yellow River basin decreased continuously. The results provide a reference for studying climate change in major river basins of China.

The construction time of concrete structures in hydraulic tunnels is long, the construction environment is complex, and there are many influencing factors. The requirements for construction quality are high, not only to meet the strength requirements, but also to meet the design requirements of erosion resistance, crack resistance, and seepage resistance according to its specific operating environment. Therefore, evaluating the construction quality of concrete structures in hydraulic tunnels is of great significance. Considering the randomness and fuzziness of factors affecting the construction quality of concrete structures in hydraulic tunnels, this paper proposes a comprehensive evaluation model based on Combined Weighting (CWM) and Uncertainty Measurement Theory (UM). The IAHP method and CRITIC method are used to determine the subjective and objective weights of evaluation indicators, combined weighting is based on the principle of minimum entropy, and the UM method is used to evaluate the construction quality level. Finally, taking a hydraulic tunnel as an example, its construction quality grade is calculated to be III according to the evaluation model proposed in this paper, which matches with the engineering reality, and a comparative study is made with the mixture element topology theory at the same time. It is verified that the evaluation model can scientifically and reasonably evaluate the construction quality level of concrete structures in hydraulic tunnels.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injure the pork product and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression, but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and host immune system, along with the involvement of virulence related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, NF-κB, JAK/STAT, apoptosis, and other modulation. The aim is to summarize the dynamic process during the ASFV infection and entry into host cell, provide a rational insight into development of vaccine and a better clear knowledge of how ASFV impacts host.

Very heavy stratiform precipitation (> 200 mm/per day) occurred in the Hokitika region on the west coast of the South Island of New Zealand on 18 June 2015, under north-westerlies with small CAPE (< 25 J/kg). Analyses of model simulations and observations showed that this heavy rainfall was due to cold front lifting enhanced by orographic lifting over the Southern Alps. At 1.5 km grid-length, the model terrain underestimated the average height of the 103 tallest mountains over the South Island by ~ 800 m. This leads to weaker orographic lifting and mountain blocking, and a faster-moving and stronger cold front in the Hokitika region. As a result, large errors in the heavy rainfall prediction occur. By increasing either the resolved or the sub-grid mountain heights, the simulated rainfall errors were largely reduced through stronger orographic lifting and mountain blocking, and a better simulation of the cold front movement and strength. All the experiments have the same “flow-over” regime with mountain waves and/or wave breaking (Fm ranges 0.61 – 1.21). However, the rainfall amount and distribution on the windward side of mountains altered significantly. Our new findings were that the Southern Alps can have significant indirect effects on heavy rainfall by altering the speed and strength of the cold front, in addition to the well-known direct dynamical effects (i.e., orographic lifting and mountain blocking). A combination of these direct and indirect effects makes the heavy rainfall simulation sensitive to mountain heights even under the same “flow-over” regime.

The European Union Water Framework Directive (2000/60/EC; WFD) aims to achieve a good ecological and chemical status of all bodies of surface water by 2027. The development of an integrated guidance on surface water chemical monitoring (e.g. WFD Guidance Document No. 7/19) has been transferred into national German law (Ordinance for the Protection of Surface Waters, OGewV). For the majority of compounds, this act requires a monthly sampling frequency to assess the chemical water quality status of a surface water body. To evaluate the representativeness of the sampling strategy under the OGewV, high-frequency online monitoring data is investigated under different sampling scenarios and compared with current, monthly grab sampling strategy. About 23 million data points were analyzed for this study, three chemical parameters (dissolved oxygen, nitrate-nitrogen, chloride concentration) and discharge data were selected from four catchment of different sizes ranging from 51391 km² to 84 km² (Elbe, Vereinigte Mulde, Neiße and two stations at Lockwitzbach). In this paper we proposed short-term online-monitoring (STOM) as a sampling alternative. STOM considers the placement of online sensors over a limited duration and return interval. In general we: (I) compare the results of conventional grab sampling with STOM, (II) investigate the different performance of STOM and grab sampling using discharge data as proxy for analyzing event-mobilized pollutants and (III) investigate the related uncertainties and costs of both sampling methods. Results show, that STOM outperforms grab sampling for parameters where minimum/maximum concentrations are required by law as the probability to catch a single extreme value is higher with STOM. Furthermore, parameters showing a pronounced diurnal pattern, like dissolved oxygen, are also captured considerably better. The performance of STOM showed no substantial improvements for parameters with small concentration variability, as nitrogen-nitrate The analysis of discharge events as a proxy parameter for event-mobilized pollutants proved that the probability of capturing samples during events is significantly increased by STOM.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and restricted interest for specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD and identifying potential therapeutic strategies. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 hours post-fertilization. After the exposure, embryos were transferred to fish water and the effects on behavior and neurotransmitters profile were analyzed at both larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. Neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the interest of this model in the study of ASD.

This study utilises NaOH to treat composite cementitious materials containing aeolian sand and zeolite powders, which were used to replace 50% of the cement in aeolian-sand concrete (ASC). The mechanical properties of treated ASC considerably improved, especially when the NaOH dosage was 4% by mass. After curing this sample (denoted as AAZC-4) for 28 d, its compressive strength improved by 17.2% and its split tensile was increased by 16.3%. Potassium feldspar and montmorillonite in zeolite powder and SiO2 in the sand were decomposed by OH− and combined with other elements to generate various silicate gels and A-type potassium zeolite crystals inside the concrete. Microscopic examination showed that the gels and crystals intertwined to fill the pores, decreasing (increasing) the percentage of large (small) pores, thus optimising the pore structure. This substantially improved the mechanical properties of ASC. Freeze–thaw salt-intrusion tests showed that the extent of mass loss, degree of damage and loss of compressive strength of AAZC-4 were similar to those of ordinary concrete but were reduced by 36.8%, 19% and 52.1%, respectively, compared with those of ASC. Therefore, AAZC-4 has sustainable working performance in the chloride ion permeable environment in cold and arid areas.

Droughts have a substantial effect on water resources, agriculture, and ecosystems on a worldwide scale. In the Mekong Delta of Vietnam, droughts exacerbated by climate change are significantly endangering the region's agricultural sustainability and output. Conventional forecasting techniques frequently do not capture the intricate dynamics of meteorological phenomena associated to drought effectively, prompting the exploration of more advanced methodologies. This work utilises artificial intelligence, par-ticularly machine learning methods like Gradient Boosting and Extreme Gradient Boosting (XGBoost), to enhance drought pre-diction in the Mekong Delta. The study utilises data from 11 meteorological stations spanning from 1990 to 2022 to create and evaluate Machine Learning models based on several climatic factors. We utilise Gradient Boosting and XGBoost algorithms to estimate the Standardised Precipitation-Evapotranspiration Index (SPEI) and evaluate their effectiveness in comparison to con-ventional forecasting techniques. The results show that Machine Learning, particularly XGBoost, surpasses traditional approaches in predicting SPEI accuracy at various time scales. XGBoost demonstrates skill in understanding the complex relationships between climatic factors, with R² values falling between 0.90 and 0.94 for 1-month forecasts. The progress highlights the potential of Machine Learning in improving drought management and adaptation tactics, proposing the incorporation of Machine Learning forecasting models into decision-making processes to enhance drought resistance in susceptible areas.

Large-scale hydrological modeling in China is challenging given the sparse meteorological stations and large uncertainties associated with atmospheric forcing data.Here we introduce the development and use of the China Meteorological Assimilation Driving Datasets for the SWAT model (CMADS) in the Heihe River Basin(HRB) for improving hydrologic modeling, by leveraging the datasets from the China Meteorological Administration Land Data Assimilation System (CLDAS)(including climate data from nearly 40000 area encryption stations, 2700 national automatic weather stations, FengYun (FY) 2 satellite and radar stations). CMADS uses the Space Time Multiscale Analysis System (STMAS) to fuse data based on ECWMF ambient field and ensure data accuracy. In addition, compared with CLDAS, CMADS includes relative humidity and climate data of varied resolutions to drive hydrological models such as the Soil and Water Assessment Tool (SWAT) model. Here, we compared climate data from CMADS, Climate Forecast System Reanalysis (CFSR) and traditional weather station (TWS) climate forcing data and evaluatedtheir applicability for driving large scale hydrologic modeling with SWAT. In general, CMADS has higher accuracy than CFRS when evaluated against observations at TWS; CMADS also provides spatially continuous climate field to drive distributed hydrologic models, which is an important advantage over TWS climate data, particular in regions with sparse weather stations. Therefore, SWAT model simulations driven with CMADS and TWS achieved similar performances in terms of monthly and daily stream flow simulations, and both of them outperformed CFRS. For example, for the three hydrological stations (Ying Luoxia, Qilian Mountain, and ZhaMasheke) in the HRB at the monthly and daily Nash-Sutcliffe efficiency ranges of 0.75-0.95 and 0.58-0.78, respectively, which are much higher than corresponding efficiency statistics achieved with CFSR (monthly: 0.32-0.49 and daily: 0.26 – 0.45). The CMADS dataset is available free of charge and is expected to a valuable addition to the existing climate reanalysis datasets for deriving distributed hydrologic modeling in China and other countries in East Asia.

Grapefruit and lemon pectin obtained from the respective waste citrus peels via hydrodynamic cavitation in water only are powerful, broad-scope antimicrobial alternatives to antibiotics against Gram-negative and -positive pathogens. Dubbed IntegroPectin, these pectic polymers functionalized with citrus flavonoids and terpenes show superior antimicrobial activity when compared to commercial citrus pectin. Similarly to commercial pectin, lemon IntegroPectin determined ca. 3 log reduction of Staphylococcus aureus cells, while an enhanced activity of commercial citrus pectin was detected in the case of Pseudomonas aeruginosa cells with a minimal bactericidal concentration (MBC) of 15 mg mL-1. Although grapefruit and lemon IntegroPectin share equal MBC in the case of P. aeruginosa cells, grapefruit IntegroPectin shows boosted activity upon exposure of S. aureus cells with a 40 mg mL-1 biopolymer concentration being sufficient to achieve complete killing of the bacterial cells. Insight on the mechanism of action of these biocompatible antimicrobials and their effect on bacterial cells, at the morphological level, were obtained indirectly through Fourier Transform Infrared spectroscopy and directly through scanning electron microscopy. In the era of antimicrobial resistance, these results are of great societal and sanitary relevance as they open new avenues to develop innovative antimicrobials for the treatment of polymicrobial infections unlikely to develop drug resistance.

Traditional concrete pavements have poor water permeability, while the strength of pervious concrete pavements is low. To solve these problems, this study designed Innovative recycled aggregate pervious concrete (I-RAPC) with controllable water permeability and high strength by using response surface methodology, and investigated the effects of different pore parameters (number, diameter, material, distribution form, etc.) on the performance of I-RAPC. And the strength discount factor method was proposed to construct the theoretical calculation model of compressive strength and pipe pore parameters, and the calculation model of water permeability coefficient was established at the same time. The results show that the fewer the number of holes and the smaller the pipe diameter of I-RAPC, the higher its compressive strength and the smaller the water permeability coefficient. The theoretical model of compressive strength can accurately evaluate the discounting effect of the pore parameters on the compressive strength of I-RAPC, and the maximum relative error is only 7.52%, and the maximum relative error of the calculation model of water permeability coefficient is only 4.42%. I-RAPC has the advantages of high strength and permeability with controllable performance, which overcomes the problems of random distribution of pore space, uncertainty of water permeability, and strength of ordinary pervious concrete.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of &lt;100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

Revealing the spatial distribution mechanism of the coupling effect between soil water and salt is essential for managing saline-alkali farmland. This study utilized the multifractal method to analyze soil water and salt under varying water content levels in arid saline-alkali farmland. Soil samples were collected on the second (S1), fifth (S2), eighth (S3), eleventh (S4), and fourteenth (S5) days after a rainfall event. The findings showed that a significant decrease in soil water content, contrasting with an increase in soil salt content throughout the soil layers post-rainfall. As water content decreased, the spatial variability of soil water initially increased from S1-3 and then decreased, while the spatial variability of soil salt decreased. The spatial distribution between soil water and salt exhibited a high correlation at S3-4 (with relative water content of soil ranging from 0.52 to 0.75) due to their coupling effect. However, soil salt was unevenly leached by rainfall at high water content levels (S1-2) and precipitated at low water content levels (S5), resulting in low spatial variability correlations between soil water and salt. This study elucidated the coupling process of soil water and salt, identifying their spatiotemporal distribution mechanism in dryland agricultural areas.

The recent availability of commercial platforms for behavioral analysis in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor response (VMR). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work we have analyzed in 143 larvae the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4,004 analyses for each behavior). Results from both behaviors were adjusted to a Random-Effects linear regression model using generalized least squares (GLS), including in the model the effect of the three variables, the second-way interactions between them and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on age of the larva and the behavioral test.

Uniform water soluble MoS2 quantum dots (WS-MSQDs) are synthesized via a sequential combination of sintering/etching/exfoliation method and solvothermal route. The obtained WS-MSQDs with average size of approximately 3.4 nm exhibit sufficient water solubility and remarkable fluorescence properties. The WS-MSQDs have been utilized as a probe for detection of Fe3+ ions with high selectivity and specificity. Furthermore, the WS-MSQDs exhibit high fluorescence stability under different conditions. Finally, the WS-MSQDs are successfully applied for the fluorescence imaging of Fe3+ in living cells, which exhibited practical potential for biomedical applications.

Lake sediment records are of great importance for understanding the evolution of watershed environments. Various studies have been carried out to constrain the depositional ages of lake sediments and examine their physical, chemical, and biological characteristics, aiming to construct historical vegetation, environment and climate patterns in Chinese lake watersheds. In this study, we obtained relevant literature on lake sediment records by searching the key word 'age-depth' from the databases – Web of Science and China National Knowledge Infrastructure (CNKI, the largest Chinese academic database). We analyzed the literature based on its type (published in a Chinese/English journal or as a Master’s/PhD thesis), period of publication, journal (if published in a journal), key authors, study area, dating scale, and main aims. The results suggest that the lakes in the plateau regions are the most popular research topic typically covering 100–200 years (short-term) and 500–30,000 years (long-term). The literature focuses on a wide range of topics, from past environmental evolution in the watershed to lake ecology, and provides a solid foundation for better understanding regional climate change and the preservation of lake environments and ecosystems. In the future, resulting data from environmental reconstruction with lake sediments will be needed to integrate with emerging information processing technologies (e.g., artificial intelligence and meta-analysis), to disentangle the complex interplay between Earth surface processes and global climate change; furthermore, strengthening interdisciplinary collaboration will deepen our comprehension of man-land relationship and promote the sustainable management of lake ecosystems in the context of global climate change.

This study develops a structure for mapping native vegetation in a transition area between Brazilian Cerrado and Atlantic Forest from integrated spatial information from the Sentinel-1 and Sentinel-2 satellites. Most studies use this data separately, however, the integrated use of optical sensors with Synthetic Aperture Radar (SAR) sensors can improve the methodology for classifying land use and land cover (LULC). The fusion of Sentinel-1 and Sentinel-2, for example, can increase the accuracy of mapping algorithms, using complementary information, such as spectral, backscattering, polarimetry, and interferometry. The study area comprises the Lobo Reservoir Hydrographic Basin, which is part of an environmental conservation unit protected by Brazilian law and with significant human development. LULC were classified, using the random forest deep learning algorithm. The classifying attributes were backscatter coefficients, polarimetric decomposition, and interferometric coherence for radar data (Sentinel-1), and optical spectral data, comprising bands in the red edge, near infrared, and shortwave infrared (Sentinel-2). The attributes were evaluated in three settings in which the SAR and optical data were evaluated separately (C1 and C2, respectively) and in an integrated manner (C3). The study found greater accuracy for C3 (96.54%), an improvement of nearly 2% compared to C2 (94.78%) and more than 40% in relation to C1 (55.73%). The classification algorithm encountered significant challenges in identifying wetlandsin C1, but performance improved in C3, enhancing differentiation by stratifying a greater number of classes during training and facilitating visual interpretation during sampling. Accordingly, the use of SAR and optical data becomes an alternative to optimize LULC mapping in tropical regions, due to the limited influence of atmosphere on images in the microwave range.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

Nitrogen (N) is an essential macro nutrient for crop growth; therefore, N deficit can greatly limit crop growth and production. In the North China Plain (NCP), winter wheat is one of the main food crops, and its yield has increased from approximately 4000 kg ha-1 to 6000 kg ha-1 in the last two decades. Determining the proper N application rates at different growth stages and in all seasons is very important for the sustainable and high production of wheat in the NCP. A field experiment with five N application rates (250, 200, 150, 100, and 40 kgN·ha-1, designated as N250, N200, N150, N100, and N40, respectively) was conducted during the 2017-2018 and 2018-2019 winter wheat seasons to investigate the effects of the N application rate on water- and fertiliz-er-utilization efficiency, and on the crop growth and yield of winter wheat under sprinkler fer-tigation conditions. The results showed that, in the N application range of 40-200 kg ha-1, crop yield and water- and fertilizer-use efficiencies increased as the N application rate increased; however, further increases in the N application rate did not have additional benefits. The N up-take after regreening of winter wheat linearly increased with crop growth. Considering the wheat yield and N-use efficiency, the optimal N application range was 200 kg ha-1, and the best top-dressing strategy was equal amounts of N applied at the regreening, jointing, and grain-filling stages. The results of this study will be useful for optimizing field N management to achieve high wheat yield production in the NCP and in regions with similar climatic and soil environment conditions.

Assessment of extreme events and climate change on reservoir inflow is important for water and power stressed countries. Projected climate is subject to uncertainties related to climate change scenarios and Global Circulation Models (GCMs’). Extreme climatic events will increase with the rise in temperature as mentioned in the AR5 of the IPCC. This paper discusses the consequences of climate change that include extreme events on discharge. Historical climatic and gauging data were collected from different stations within a watershed. The observed flow data was used for calibration and validation of SWAT model. Downscaling was performed on future GCMs’ temperature and precipitation data, and plausible extreme events were generated. Corrected climatic data was applied to project the influence of climate change. Results showed a large uncertainty in discharge using different GCMs’ and different emissions scenarios. The annual tendency of the GCMs’ is bi-vocal: six GCMs’ projected a rise in annual flow, while one GCM projected a decrease in flow. The change in average seasonal flow is more as compared to annual variations. Changes in winter and spring discharge are mostly positive, even with the decrease in precipitation. The changes in flows are generally negative for summer and autumn due to early snowmelt from an increase in temperature. The change in average seasonal flows under RCPs’ 4.5 and 8.5 are projected to vary from -29.1 to 130.7% and -49.4 to 171%, respectively. In the medium range (RCP 4.5) impact scenario, the uncertainty range of average runoff is relatively low. While in the high range (RCP 8.5) impact scenario, this range is significantly larger. RCP 8.5 covered a wide range of uncertainties, while RCP 4.5 covered a short range of possibilities. These outcomes suggest that it is important to consider the influence of climate change on water resources to frame appropriate guidelines for planning and management.

Pea shoots is a popular vegetable in certain regions of the world due to their unique taste and abundance of health-promoting phytochemicals. The perishable nature and susceptibility of root rot of pea shoots necessitate a new soilless production system located close to the market. This study compared the growth of pea shoots using various cultivation methods in LED plant factory. The results showed that early topping (4 days after transplanting, ET) promoted early harvest compared to later topping (20 days after transplanting, LT) and increased the number of harvested shoots by extending the harvest time to 2.8 times, ultimately resulting in a substantial yield improvement. Moreover, the yield of ET with lower planting density (72 plants m-2, ET-LD) was 8.7% higher than ET with higher planting density (126 plants m-2, ET-HD). Particularly, the average fresh weight of individual pea shoots under ET-LD exceeded that of ET-HD by 48.9%. It is advisable to consider adopting ET-LD for the cultivation of pea shoots in LED plant factory. Based on ET-LD, the yield, nutritional quality, and light use efficiency of pea shoots were further explored at different stages under three levels of light intensity (50, 100, 150 μmol m-2 s-1). Contrasted against the light intensity of 50 μmol m-2 s-1, the average fresh weight per pea shoots, number of harvested, and total fresh yield under light intensity of 150 μmol m-2 s-1 treatment increased by 60.2%, 62.8%, and 165.1%, respectively. Meanwhile, the fresh weight per pea shoots, photosynthetic capacity, soluble sugar and vitamin C levels in leaves, as well as light use efficiency and photon yield, initially increased and then decreased with the extension of the planting period. Among these, soluble sugar, LUE, and PY started to decrease after reaching the maximum value at 60-70 days after transplanting. In conclusion, light intensity of 150 μmol m-2 s-1 with a photoperiod of 16 h d-1 using LEDs, combined with early topping within a planting period of 60-70 days, proves to be suitable for the hydroponic production of pea shoots in LED plant factory.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

Bladder cancer (BC) is one of the most lethal genitourinary malignancies owing to its propensity for recurrence and poor survival. The biochemical pathway, signal transducer and activator of transcription 3 (STAT3), has gained significance as a molecular pathway that promotes proliferation, invasion, and chemoresistance. In this study, we explored the targeting of STAT3 with TTI-101 and SH5-07 in bladder cancer (BCa) and elucidated the mechanisms in three-dimensional (3D) spheroid and tumoroid models. We optimized the growth of spheroids from human, rat, and mouse BCa cell lines (J82, NBT-II, and MB49, respectively), and tumoroids from BBN (N-butyl-N-(4-hydroxybutyl)-nitrosamine) induced rat bladder tumors. Cell viability was assessed using MTT and trypan blue assays. ATP production, ROS production, and calcium AM (CA)/EtBr staining were used to measure the spheroid and organoid inhibition and mitochondrial function. Western blot analysis was performed to evaluate the pharmacodynamic markers involved in cell proliferation, apoptosis, cancer stem cells (CSCs), and STAT3 signaling in BCa. We found that targeting STAT3 (using TTI-101 and SH5-07) significantly reduced the proliferation of BCa spheroids, and tumoroids, which was accompanied by decreased expression of pSTAT3, Cyclin D1, and PCNA. Our data also demonstrated that treatment with STAT3 inhibitors induced ROS production and cell death in BCa spheroids and organoids. STAT3 inhibition induced cell death was associated with the activation of caspase 3/7 and PARP cleavage. Moreover, TTI-101 and SH5-07 targets cancer stem cells by downregulating the expression of CD44 and CD133 in 3D models. This study provides the first evidence for the prevention of bladder cancer with small-molecule inhibitors TTI101 and SH5-07 via suppression of CSCs and STAT3 signaling.

The Cauto River Basin (CRB), the heartland of Cuban agriculture, has been hit hard by drought and water shortage. In response to this pressing issue, this study provides a comprehensive as-sessment of water supply, demand and balance within the Cauto River Basin, considering the baseline and projected socio-economic and climatic conditions by coupling of SWAT and WEAP models. The obtained results reveal that the annual flow in the CRB is projected to slightly de-crease (2.5%) in which the reduction in the rainy season (3.1%) is higher than that in the dry sea-son (1.3%). Total water demand in the baseline scenario is around 1.194 billion m3, dominated by agriculture (96%), with rice crop requiring nearly half. For the future scenario of 2050, the study shows a 16.6% surge in demand to 1.394 billion m3, driven by climate change and agricultural expansion. However, domestic use decreases by 10% due to population reduction. Water deficit in the future is projected to increase by 52% from 172.4 to 262.7 million m3 due to rising water demand and declining water supply. This study shows that integrating a hydrological model into a water allocation model is a promising approach to estimate the water supply, demand and balance, which is a crucial component of water resources management.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

In the present work report, the MgAl₂O₄and the Ag/MgAl₂O₄ samples were successfully synthesized by the modified hydrothermal and the isovolumetric impregnation methods, respectively. The structural properties of the prepared samples were systematically characterized by XRD, SEM, TEM, DRS, XPS and et al techniques. The photocatalytic degradation of methylene blue by the Ag/MgAl₂O₄ and MgAl₂O₄ samples was comparatively studied under UV lamp irradiation. The results revealed that the prepared Ag/MgAl₂O₄ (pH=6) samples were the most active among the samples in photocatalytic of methylene blue. Under UV lamp irradiation, the Ag/MgAl₂O₄ (pH=6) photodegradation of methylene blue reached to 89.6% within 120 min. And the Ag/MgAl₂O₄ (pH=6) complex photocatalysts displayed a high photochemical stability under repeated irradiation. Repeated irradiate the Ag/MgAl₂O₄ (pH=6) compound, which indicated it had a high photochemical stability.

One of the G protein-coupled receptors, C-C chemokine receptor 5 (CCR5), is an important regulator for the activation of T and B lymphocytes, dendritic cells, natural killer cells, and macrophages. Upon binding to the ligands, CCR5 activates downstream signaling, which plays critical roles in the innate and adaptive immune response through the promotion of lymphocyte migration and the secretion of pro-inflammatory cytokines. Anti-CCR5 monoclonal antibodies (mAbs) have been developed and evaluated in clinical trials for tumors and inflammatory diseases. In this study, we developed novel mAbs for mouse CCR5 (mCCR5) using the N-terminal peptide immunization. Among the established anti-mCCR5 mAbs, C₅Mab-4 (rat IgG_2a, kappa) and C₅Mab-8 (rat IgG₁, kappa), recognized mCCR5-overexpressed Chinese hamster ovary-K1 (CHO/mCCR5) and an endogenously mCCR5-expressing cell line (L1210) by flow cytometry. The dissociation constant (K_D) values of C₅Mab-4 and C₅Mab-8 for CHO/mCCR5 were determined as 3.5 × 10⁻⁸ M and 7.3 × 10⁻⁹ M, respectively. Furthermore, both C₅Mab-4 and C₅Mab-8 could detect mCCR5 by western blotting. These results indicated that C₅Mab-4 and C₅Mab-8 are useful for detecting mCCR5 by flow cytometry and western blotting and provide a possibility to obtain the proof of concept in preclinical studies.

Water-soluble and cytocompatible polymers were investigated to enhance a transporting efficiency of biomolecules into cells in vitro. The polymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) unit, a hydrophobic monomer unit, and a cationic monomer unit bearing an amino group were synthesized for complexation with model biomolecules, siRNA. The cationic MPC polymer was shown to interact with both siRNA and the cell membrane and was successively transported siRNA into cells. When introducing 20 − 50 mol% hydrophobic units into the cationic MPC polymer, transport of siRNA into cells. The MPC units (10 − 20 mol%) in the cationic MPC polymer were able to impart cytocompatibility, while maintaining interaction with siRNA and the cell membrane. The level of gene suppression of the siRNA/MPC polymer complex was evaluated in vitro and it was as the same level as that of a conventional siRNA transfection reagent, whereas its cytotoxicity was significantly lower. We concluded that these cytocompatible MPC polymers may be promising complexation reagent for introducing biomolecules into cells, with the potential to contribute to future fields of biotechnology, such as in vitro evaluation of gene functionality, and the production of engineered cells with biological functions.

Natural polluted insulator surfaces are always coated with various kinds of soluble constituents, and those constituents affect flashover performance differentially. Currently this fact is not considered either in laboratory experiments or field pollution degree measurements, causing the existing insulation selection method to be deficient. In this paper a systematical research on insulator flashover voltage gradient correction involving types of soluble pollution constituents was presented. Taking typical type glass insulator as the sample, its flashover tests polluted by typical soluble chemicals NaCl, NaNO₃, KNO₃, NH₄NO₃, MgSO₄, Ca(NO₃)₂ and CaSO₄ were carried out. Then the flashover gradient correction was made combining the flashover performance of each soluble constituent, the ESDD contribution of the seven constituents, as well as the saturation performance of CaSO₄. The correction was well verified with the flashover test results of insulator polluted by three types of soluble mixture. Research results indicate that the flashover gradient correction method proposed by this paper performs well in reducing the calculating error. It is recommended to carry out component measurements and flashover gradient correction to better select outdoor insulation configuration.

Researches on the runoff and sediment reduction effects of soil and water conservation measures are being on the rise, which is of great significance for carrying out strategic on soil and water conservation in the Yellow River Basin. Through the analysis of various soil and water conserva-tion measures, runoff, sediment, and rainfall datas in the Sanchuan River Basin from 1960 to 2019, we use the lagrange multiplier method to determining the threshold year of soil and water con-servation measures on runoff and sediment processes. The preliminary conclusion is as follows: The trend of flood season rainfall and annual rainfall in the Sanchuan River Basin is consistent. The 10-year average rainfall in each periods indicates that before 2000, it gradually decreased and then significantly increased. The 10-year average runoff showed a gradual decrease before 2010, followed by a sudden increase, while the 10-year average sediment has shown a decreasing trend years by years, especially after the centralized treatment period. Terrace and dam measures show a trend of first decreasing, then increasing, and then approaching stability during different treat-ment periods, while the trend of forest and grass measures is slightly decreasing and then in-creasing rapidly. The runoff and sediment reduction effects of various soil and water conservation measures during different treatment periods indicate that the runoff reduction effect reached its peak in 2005, while the sediment reduction benefit reached its best in 2015. Based on the compre-hensive benefits of runoff and sediment regulation, 2015 are considered as the threshold year for various soil and water conservation measures, with each measure areas being 4.86 × 104, 17.91 × 104, 1.20 × 104, and 0.83 × 104hm2, respectively. The research results will have certain reference significance for the high-quality development of soil and water conservation in the Yellow River Basin.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

Salinity, resulting from climate change and excessive mineral fertilization, burdens farmers and negatively impacts soil and water ecosystems in the Northeastern Nile Delta. Organic and biological approaches are crucial for addressing these issues. This study examined the effects of individual and combined inoculations with cyanobacteria, yeast, and Arbuscular Mycorrhizal Fungi (AMF), with or without K-humate, on enhancing salinity tolerance, increasing yield, and improving crop quality of wheat and faba bean. The aim was to reduce NPK mineral fertilizer application rates to 25% of recommended doses. An economic evaluation was also conducted. In a preliminary laboratory experiment, the interactive effects of these microbiomes on the production of plant antioxidant enzymes and soil enzymes were investigated under salinity stress. Results showed that co-inoculation, especially with K-humate, yielded superior outcomes compared to individual inoculations. The laboratory experiment findings were confirmed by a field trial conducted in saline-alkaline soil in the Northeastern Nile Delta region. The study found that the integrated inoculation of cyanobacteria, yeast, and mycorrhizae with K-humate, along with 25% mineral NPK fertilization enhanced microbial activity, including AMF colonization, spore density, and total bacteria, cyanobacteria, and yeast counts in the plant rhizosphere. It also increased soil enzyme activity, improving soil fertility compared to individual or mineral control treatments. This integration resulted in wheat yields of 2.77 tons/ha and faba bean yields of 4.75 tons/ha. Crop quality improved, with higher levels of nitrogen, potassium, phosphorus, and protein in wheat grains and faba bean seeds. Microbiomes inoculation increased potassium uptake over sodium, enhancing the potassium/sodium ratio and salt stress tolerance. This approach reduces reliance on costly mineral fertilizers by up to 75%, enabling economically viable cultivation in marginal lands. These sustainable practices optimize resource utilization, maximize economic efficiency, and preserve natural resources.

In order to improve contrast and restore color for underwater image captured by camera sensors without suffering from insufficient details and color cast, a fusion algorithm for image enhancement in different color spaces based on contrast limited adaptive histogram equalization (CLAHE) is proposed in this article. The original color image is first converted from RGB color space to two different special color spaces: YIQ and HSI. The color space conversion from RGB to YIQ is a linear transformation, while the RGB to HSI conversion is nonlinear. Then, the algorithm separately operates CLAHE in YIQ and HSI color spaces to obtain two different enhancement images. The luminance component (Y) in the YIQ color space and the intensity component (I) in the HSI color space are enhanced with CLAHE algorithm. The CLAHE has two key parameters: Block Size and Clip Limit, which mainly control the quality of CLAHE enhancement image. After that, the YIQ and HSI enhancement images are respectively converted backward to RGB color. When the three components of red, green, and blue are not coherent in the YIQ-RGB or HSI-RGB images, the three components will have to be harmonized with the CLAHE algorithm in RGB space. Finally, with 4 direction Sobel edge detector in the bounded general logarithm ratio operation, a self-adaptive weight selection nonlinear image enhancement is carried out to fuse YIQ-RGB and HSI-RGB images together to achieve the final fused image. The enhancement fusion algorithm has two key factors: average of Sobel edge detector and fusion coefficient, and these two factors determine the effects of enhancement fusion algorithm. A series of evaluate metrics such as mean, contrast, entropy, colorfulness metric (CM), mean square error (MSE) and peak signal to noise ratio (PSNR) are used to assess the proposed enhancement algorithm. The experiments results showed that the proposed algorithm provides more detail enhancement and higher values of colorfulness restoration as compared to other existing image enhancement algorithms. The proposed algorithm can suppress effectively noise interference, improve the image quality for underwater image availably.

This study investigates the concentrations of physicochemical and heavy metal contaminants in the groundwater of the Middle Awash Basin, Ethiopia, to inform targeted water management strategies. A total of 32 groundwater samples were collected from 16 stations via piezometers and boreholes at the end of both the dry (June 2021) and wet (October 2021) seasons. Utilizing Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Atomic Absorption Spectroscopy (AAS), and in situ metering, 22 physicochemical and 24 heavy metal parameters were analyzed. The data revealed significant levels of contamination; notably, sample GW11 had extraordinarily high concentrations of total dissolved solids (10,826 mg/L), strontium (908 µg/L), molybdenum (802.4 µg/L), zinc (6060 µg/L), and electrical conductivity (15,645 µS/cm), while GW12 exhibited elevated levels of aluminum (2615 µg/L), zinc (4446 µg/L), and arsenic (117.2 µg/L). Contaminants such as arsenic, vanadium, gallium, lithium, rubidium, chromium, manganese, copper, and zinc were found enriched in groundwater near Lake Beseka, influenced by agricultural runoff from sugarcane plantations and agro-industry activities. Over half of the groundwater sources were unsuitable for drinking, posing significant health risks to local communities that rely heavily on these sources due to limited access to clean surface water. The findings emphasize the urgent need for comprehensive groundwater management and remediation plans in the Middle Awash region to ensure safe and sustainable water use, particularly addressing the variation in contamination levels influenced by Lake Beseka. These measures are critical to protect public health and support local development in the face of ongoing environmental and anthropogenic pressures.

Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a systematic review of research studies published over the last three years. We found 156 relevant studies. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Albeit medical cannabis reduced depression in most studies, none of these were placebo controlled. In clinical studies published in the same period, placebo also ameliorated depression and in addition, the average effect size of placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.

Rising organic charge in northern freshwaters is attributed to increasing levels of Dissolved Natural Organic Matter (DNOM) and shifts in water chemistry. Organic charge concentration may be determined by charge balance calculations (Org.-) or modelled (OAN-) using the conceptual Oliver and Hruška models based on the density of weak acid functional sites (SD) present in DNOM. The charge density (CD) is governed by the SD and protonation and complexation reactions on the functional groups. The models use this SD as a key parameter in empirically fitting the model to Org.-. Utilizing extensive datasets of water chemistry, this study shows that spatial and temporal differences in SD and CD are influenced by variations in the humic-to-fulvic ratio of DNOM and the organic aluminum (Al) complexation, as well as the mole fraction of CD to SD governed by the acidity. Site median SD obtained for 44 long-term monitored acid-sensitive lakes was 11.1 and 13.9 µEq/mg C for the Oliver and the Hruška model, respectively. During the 34 years of monitoring the CD increased by 70%, likely due to rising pH and declining Al complexation with DNOM. Present-day median SD values for the Oliver and Hruška models in 16 low-order streams are 13.8 and 15.8 µEq/mg C, respectively, and 10.8 and 12.5 µEq/mg C, respectively, in 10 high order rivers.

In contrast to “frank” pathogens, like Salmonella entrocolitica, Shigella dysenteriae, and Vibrio cholerae, that always have a probability of disease, “opportunistic” pathogens are organisms that cause an infectious disease in a host with a weakened immune system and rarely in a healthy host. Historically, drinking water treatment has focused on control of frank pathogens, particularly those from human or animal sources (like Giardia lamblia, Cryptosporidium parvum, or Hepatitis A virus), but in recent years outbreaks from drinking water have increasingly been due to opportunistic pathogens. Characteristics of opportunistic pathogens that make them problematic for water treatment include: 1) they are normally present in aquatic environments, 2) they grow in biofilms that protect the bacteria from disinfectants, and 3) under appropriate conditions in drinking water systems (e.g., warm water, stagnation, low disinfectant levels, etc.) these bacteria can amplify to levels that can pose a public health risk. The three most common opportunistic pathogens in drinking water systems include Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa. This report focuses on these organisms to provide information on their public health risk, occurrence in drinking water systems, susceptibility to various disinfectants and other operational practices (like flushing and cleaning of pipes and storage tanks). In addition, information is provided on a group of nine other opportunistic pathogens that are less commonly found in drinking water systems, including Aeromonas hydrophila, Klebsiella pneumoniae, Serratia marcescens, Burkholderia pseudomallei, Acinetobacter baumannii, Stenotrophomonas maltophilia, Arcobacter butzleri, and several free-living amoebae including Naegleria fowleri and species of Acanthamoeba. The public health risk for these microbes in drinking water is still unclear, but in most cases, efforts to manage Legionella, mycobacteria, and Pseudomonas risks will also be effective for these other opportunistic pathogens. The approach to managing opportunistic pathogens in drinking water supplies focuses on controlling the growth of these organisms. Many of these microbes are normal inhabitants in biofilms in water, so the attention is less on eliminating these organisms from entering the system and more on managing their occurrence and concentrations in the pipe network. With anticipated warming trends associated with climate change, the factors that drive the growth of opportunistic pathogens in drinking water systems will likely increase. It is important, therefore, to evaluate treatment barriers and management activities for control of opportunistic pathogen risks. Controls for primary treatment, particularly for turbidity management and disinfection, should be reviewed to ensure adequacy for opportunistic pathogen control. However, the major focus for the utility’s opportunistic pathogen risk reduction plan is the management of biological activity and biofilms in the distribution system. Factors that influence the growth of microbes (primarily in biofilms) in the distribution system include, temperature, disinfectant type and concentration, nutrient levels (measured as AOC or BDOC), stagnation, flushing of pipes and cleaning of storage tank sediments, and corrosion control. Pressure management and distribution system integrity are also important to the microbial quality of water but are related more to the intrusion of contaminants into the distribution system – rather than directly related to microbial growth. Summarizing the identified risk from drinking water, the availability and quality of disinfection data for treatment, and guidelines or standards for control showed that adequate information is best available for management of L. pneumophila. For L. pneumophila the risk for this organism has been clearly established from drinking water, cases have increased worldwide, and it is one of the most identified causes of drinking water outbreaks. Water management best practices (e.g., maintenance of a disinfectant residual throughout the distribution system, flushing and cleaning of sediments in pipelines and storage tanks, among others) that have been shown to be effective for control of L. pneumophila in water supplies. In addition, there are well documented management guidelines available for the control of the organism in drinking water distribution systems. By comparison, management of risks for Mycobacteria from water are less clear than for L. pneumophila. Treatment of M. avium is difficult due to its resistance to disinfection, the tendency to form clumps and attachment to surfaces in biofilms. Additionally, there are no guidelines for management of M. avium in drinking water and one risk assessment study suggested a low risk of infection. The role of tap water in the transmission of the other opportunistic pathogens is less clear and in many cases actions to manage L. pneumophila (e.g., maintenance of a disinfectant residual, flushing, cleaning of storage tanks, etc.) will also be beneficial in helping to manage these organisms as well.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

The Lower Mekong Basin has had extensive hydropower dam development, which changes hydrologic conditions and threatens the exceptional aquatic biodiver-sity. This study quantifies the degree of hydrologic change between pre-impact (1965-1968) and post-impact (2018-2021) peak hydropower development in two major tributaries of the Lower Mekong Basin, the Sekong River with the fewest dams and the Sesan River with the most dams. Both rivers historically supported migratory fishes. We use daily pre- and post-impact data and the Indicators of Hydrologic Alteration framework to evaluate streamflow changes from dam development. We found signifi-cant changes in low and high magnitude flows in the pre- and post-impact periods of dam development. For the Sekong River, minimum flow had large fluctuations that ranged 290% to 412% more than the pre-impact period, while the Sesan River ranged 120% to 160% more than pre-impact. Dry season flows increased by 200±63% on av-erage in the Sekong River, which is caused by releases from upstream dams. Mean-while, Sesan River dry season flows increased by 100±55% on average. This study in-dicates that seasonal flow changes and extreme flow events occurred more frequently in the two basins following dam construction, which may threaten the ecosystem func-tions.

Considering characteristics of high river density, special underlying surface in plain river network region, and municipal drainage system function, river network drainage unit model is proposed, which is defined as a region surrounded by main river or embankment. Flood storage variety and control projects regulation of small rivers in each unit is simulated. With drainage catchment as an object, according to its drainage capacity, simplified municipal drainage model was developed. Coupling river network drainage unit model, simplified municipal drainage model and 2D flood routing model, urban flood analysis model for plain tidal river network region was developed, which could be applied to analyzing flood from upstream river, storm surge and local rainfall. Demonstration research was carried out in Puxi flood protected area in Shanghai.

Understanding platelet functionality has undergone a sea change in the last decade. No longer are platelets viewed simply as regulators of haemostasis; they are now acknowledged to be pivotal in coordinating the inflammatory and immune responses. This expanded role for platelets brings new opportunities for controlling a range of health conditions, targeting platelet activation and their interactions with other vascular cells. Antiplatelet drugs may be of wider utility than ever expected but often cause too strong a platelet suppression to be used out of clinical settings. Dietary antiplatelets represent a nutritional approach that can be efficacious while safe for general use. Here we review potential new uses for dietary antiplatelets outside the field of cardiovascular health, with specific reference to the water-soluble tomato extract Fruitflow®. Uses in different aspects of inflammation and immune function are discussed, highlighting exercise-induced inflammation, mediating the effects of air pollution, and controlling thrombotic aspects of the immune response. Potential future developments in women’s health, erectile dysfunction, and the allergic response give an indication of how wide-ranging the utility of dietary antiplatelets can possibly be.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

In this study, the effects of grain size and gradation of riprap, overtopping flow depth and downstream slope of embankment on scouring and deposition characteristics at the downstream toe of the embankment was investigated. For the experiment, three different downstream slopes (1:2, 1:3, and 1:4), three different overflow depths (1, 2, and 3 cm), and three different sizes (d₅₀ of 16.41 mm, 8.48 mm, and 3.39 mm herein referred as No.5, 6 and 7 respectively) of riprap particles, respectively, were used in the laboratory. The experimental results demonstrated that the scour depth and deposition height increased with increasing energy head for each downstream slope condition. Among the three particle sizes, for No. 5 size particle shows the lowest scour depth and highest deposition height. For the 1:2 slope, the No. 5 particle size could resist scour 62% and 75% less than that of the No. 6 and No. 7 particles, respectively. For the 1:3 slope case, this was 31% and 46%, and for the 1:4 slope case, this was 39% and 49% less than the No. 6 and No. 7 size particles, respectively.

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H₂Mab-250/H₂CasMab-2. In flow cytometry and immunohistochemistry, H₂Mab-250 reacted with HER2-positive breast cancer cells but did not show the reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG₁ version of H₂Mab-250 (H₂Mab-250-hG₁) possesses compatible in vivo antitumor effects against breast cancer xenografts with trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H₂Mab-250-hG₁ and trastuzumab. Both H₂Mab-250-hG₁ and trastuzumab showed ADCC activity against CHO/HER2 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed that trastuzumab showed a more significant ADCC effect compared to H₂Mab-250-hG₁. Importantly, H₂Mab-250-hG₁ exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in mouse IgG_2a types of both H₂Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H₂Mab-250-hG₁ and trastuzumab and indicate the future direction for the clinical development of H₂Mab-250-hG₁ against HER2-positive tumors.

The bivalve mollusc Pinna nobilis, endemic to the Mediterranean Sea, since 2016 is vanishing from the whole basin because of an infection by multiple pathogens that caused mass mortality events. In the Eastern Mediterranean some little populations seem to be resistant to the infection. These individuals could represent the only possibility for the species to recolonize now desert habitats. Thus, according to the recommendations of IUCN, the looking for living specimens of P. nobilis is a priority. As a result of a monitoring activity carried out in 2022-2024, along the Ionian cost of Apulia, in Southern Italy, the species has completely disappeared leaving only empty shells. Concurrent to the vanishing of P. nobilis, its congeneric P. rudis, resistant to the infection, seems to be taking advantage, becoming more common and colonizing habitats once exclusive of P. nobilis. In fact, from different areas of the Mediterranean, the sightings of P. rudis are increasing, together with the discovering of individuals exhibiting morphological traits that are a mixing between the two species. In some cases, these morphological features are not easy to detect, anyway the presence of these hybrids, resistant to the infection, is important for the conservation of the species.

In the era of mounting water scarcity, particularly in arid regions, the agricultural sector is striving to optimize the water resource management practices. Treated wastewater (TWW) has emerged as a viable alternative to freshwater for irrigation, offering a sustainable solution to water conservation. However, ensuring the safety and quality of TWW is paramount to safeguard for both crop health and environmental integrity. Electrical conductivity (EC), a critical factor in assessing TWW suitability for irrigation, can significantly impact crop yields and soil health since it is directly linked to the concentration of dissolved salts and ions. Therefore, this study delves into the development of advanced predictive models for EC assessment by employing supervised machine learning (ML) techniques like the Support Vector Regression (SVR), Adaptive Network-based Fuzzy Inference System (ANFIS), and Multiple Linear Regression (MLR). The TWW samples collected from Al-Qatif area, Saudi Arabia were assessed in the lab through a sensor-based real-time monitoring system integrated with Internet of Things (IoT) network and a multiprobe device. The key water quality parameters assessed involved, temperature (T), pH, Oxidation Reduction Potential (ORP), Resistivity (RES), Total Dissolved Solids (TDS), Salinity and Turbidity which served as the foundation for these models, given their profound influence on and their anticipated impact on EC levels. Following feature selection, two distinct model combinations were identified for the SVR, ANFIS and MLR models. Furthermore, to evaluate prediction performance, four statistical criteria, including coefficient of determination (R²), correlation coefficient (R), mean square error (MSE), and root mean square error (RMSE), were employed. Overall, the comparative performance results proved that ANFIS-M2 indicated the strongest predictive capability with the R² value of 0.99572 and 0.75145 and the RMSE values of 0.00965 and 0.01134, respectively in both calibration and verification stages.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Channel bends are one of the most important characteristic features of natural streams. These bends often create the conditions for a hyporheic zone, which has been recognized as a critical component of stream ecosystems. The streambed vertical hydraulic conductivity (K_v), vertical hydraulic gradient (VHG) and Darcian flux (DF) in the hyporheic zone were estimated at 61 locations along a channel bend of the Beiluo River during July 2015 and January 2016. All the streambed attributes showed great spatial variability along the channel bend. Both upward fluxes and downward fluxes occurred during the two test periods, most of studied stream sections were controlled by downwelling, indicating stream water discharge into the subsurface. The average downward flux was higher at the downstream side than at the upstream side of the channel bend, especially in July 2015. The distribution of streambed sediment grain size has a significant influence on the variability of K_v; high percentages of silt and clay sediments generally lead to low K_v values. Higher K_v at the depositional left bank at the upstream site shifted toward the erosional right bank at the downstream site, with K_v values positively correlated with the water depth. This study suggested that the variabilities of K_v and VHG were influenced by the stream geomorphology and that the distribution of K_v was inversely related, to a certain extent, to the distribution of VHG across the channel bend. K_v and VHG were found to have opposite effects on the DF, and the close relationship between K_v and DF indicated that the water fluxes were mainly controlled by K_v.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

Crop production in Afghanistan suffers from limited phosphorus (P) availability, which severely hinders national agriculture sustainability. This present study hypothesized that deep fertilizer placement could significantly enhance uptake of immobile P and thus tissue P accumulation and crop yield. A two-year pot experiment growing two maize (Zea mays) hybrid cultivars (Xida-789 and Xida-211) was therefore conducted to test these hypotheses under three contrasting fertilizer placement methods (broadcast, side band, and deep band). In doing so, P concentrations in both maize tissues and soils were compared at 45, 60, and 115 days after sowing (DAS) under nine combinations of nitrogen (N) and P fertilizer rates (kg ha-1: N112P45, N112P60, N112P75, N150P45, N150P60, N150P75, N187P45, N187P60, N187P75). Results have shown that deep band placement significantly increased P uptake efficiency, leading to greater P concentration and accumulation in maize tissues compared to other two fertilization methods. This improved P uptake was attributed to several factors associated with deep placement, including reduced P fixation, enhanced root access to P, and moisture availability for P uptake. Additionally, deep band placement combined with higher N application rates (N187 and N150) further enhanced plant P uptake by promoting P availability and utilization mechanisms. Deep band placement also resulted in significantly higher total soil P, Olsen-P, and P use efficiency than broadcast and side band methods, indicating a more efficient P fertilization strategy for maize that can improve growth and yield. This present study also found positive correlations between P concentration in plant organs and soil Olsen-P, highlighting the importance of adequate soil P levels for optimal plant growth. Overall, our results have showed that deep band fertilizer placement emerged as a superior strategy for enhancing P uptake efficiency, utilization, and maize productivity compared to broadcast and side band placement. This approach can potentially optimize P fertilizer utilization, improve maize growth and yield, while minimizing environmental P losses associated with broadcast applications.

Adaptation to climate change is being addressed in many domains. This means that there are multiple perspectives on adaptation; often with differing visions resulting in disconnected responses and outcomes. Combining singular perspectives into coherent, combined perspectives that include multiple needs and visions can help to deepen the understanding of various aspects of adaptation and provide more effective responses. Such combinations of perspectives can help to increase the range and variety of adaptation measures available for implementation or avoid maladaptation compared with adaptations derived from a singular perspective. The objective of this paper is to present and demonstrate a framework for structuring the local adaptation responses using the inputs from multiple perspectives. The adaptation response framing has been done by: (i) contextualizing climate change adaptation needs; (ii) analyzing drivers of change; (iii) characterizing measures of adaptation; and (iv) establishing links between the measures with a particular emphasis on taking account of multiple perspectives. This framework was demonstrated with reference to the management of flood risks in a case study Can Tho, Vietnam. The results from the case study show that multiple perspective framing of adaptation responses enhance the understanding of various aspects of adaptation measures, thereby leading to flexible implementation practices.

The primary objective of this study was to demonstrate the potential of digital image analysis as a tool to identify microplastic (MP) particles in surface waters and to facilitate their characterisation in terms of 2D and 3D morphology. Digital image analysis preceded by microscopic analysis was used for an exhaustive quantitative and qualitative evaluation of MPs isolated from the Vistula river. Using image processing procedures, 2D and 3D shape descriptors were determined. The Principal Components Analysis (PCA) was used to interpret the relationships between the parameters studied, characterising MP particle geometry, type and colour. This multivariate analysis of the data allowed 3 or 4 main factors to be extracted, explaining approximately 90% of the variation in the data characterising MP morphology. It was found that the first principal component for granules, flakes and films was largely represented by strongly correlated with 2D shape descriptors (area, perimeter, equivalent area diameter) and 3D shape descriptors (CSF, Compactness, Dimensionality). Considering the scraps, PC1 was represented by only five of the above descriptors, and the Compactness variable had the largest contribution to PC2. In addition, for granules, flakes and films, a relationship between 2D shape and the colour of their particles could be observed. For the most numerous MP group identified of multicoloured scraps, no such association was found. The results of our study can be used for further multivariate analysis regarding the presence of microplastic floating on the river surface, with a particular focus on particles of secondary origin. This is of key importance for optimising future efforts in conducting small-scale and multidimensional monitoring of and reducing plastics in the aquatic environment.

A new type of artificial block is proposed by modifying the traditional block. Based on the physical model experiment, the wave reflection and run-up characteristics of the new ecological blocks under regular waves were examined, and the influence of the height of the "planting trough" border on the hydrodynamic properties was analyzed. The results indicate that the wave reflection and run-up would decrease with a decrease in the breakwater slope. As wave height increases, wave run-up increases, and the reflection coefficient falls. Wave reflection and run-up increase with an increasing wave period. The relative depth of the water has a smaller impact on the wave reflection than the wave run-up. The reflection coefficient of the new ecological blocks is consistently lower than that of the conventional and continues to decrease as the border of the "planting trough" is raised. The raised borders prevent water loss in the trough, resulting in no significant improvement in the wave run-up performance of the new blocks. The reflection coefficient and the relative run-up R/H gradually increase with the average wave breaking parameter ξ increase. The crude permeability coefficients for the new blocks, New Heights 1 and New Heights 2, are 0.53, 0.53, and 0.54, respectively.

Environmental monitoring programs rely on periodic spot sampling at specific locations, followed by laboratory analysis, aiming at the evaluation of water quality at a catchment scale. For this purpose, automatic telemetric stations for specific parameters have been installed by the Institute of Marine Biological Resources and Inland Waters of Hellenic Centre for Marine Research (IMBRIW-HCMR) within several Greek rivers and lakes, providing continuous and temporal monitoring possibilities. Nevertheless, the employment of unmanned surface vehicles (USV) equipped with integrated sensors represents a tool valuable to several monitoring strategies, offering enhanced temporal and spatial coverage over specific timeframes, allowing for targeted examination of sites or events of interest. The USVs have been deployed by Athens Water and Sewerage Company (EYDAP) as a cost-effective tool for the environmental monitoring of surface water bodies of interest, with emphasis on the spatial fluctuations of chlorophyllα, electrical conductivity, dissolved oxygen and pH, observed in Koumoundourou Lake and rivers Acheloos, Asopos and Kifissos. The effectiveness of an innovative heavy metal (HM) system installed in the USV for thein situ determination of copper and lead was also evaluated herewith. The results obtained demonstrate that both the timely detection of potential pollution from both anthropogenic activities and natural processes as well as the monitoring of inland waters are made feasible through the employment of USV.

Climate simulations in West Africa have been attributed with large uncertainties. Global climate projections are not consistent with changes in observations at the regional or local level of the Niger basin, making management of hydrological projects in the basin uncertain. This study evaluates the potential of using the quantile mapping bias correction to improve the Coupled Model Intercomparison Project (CMIP5) outputs for use in hydrology impact studies. Rainfall and temperature projections from 8 CMIP5 Global Climate Models (GCM) were bias corrected using the quantile mapping approach. Impacts of climate change was evaluated with bias corrected rainfall, temperature and potential evapotranspiration (PET). The IHACRES hydrological model was adapted to the Niger basin and used to simulate impacts of climate change on discharge under present and future conditions. Bias correction significantly improved the accuracy of rainfall and temperature simulations compared to observations. Nash coefficient (NSE) for monthly rainfall comparisons of 8 GCMs to the observed was improved by bias correction from 0.69 to 0.84. The standard deviations among the 8 GCM rainfall data were significantly reduced from 0.13 to 0.03. Increasing rainfall, temperature, PET and river discharge were projected for all GCMs used in this study under the RCP8.5 scenario. These results will help improving projections and contribute to the development of sustainable climate change adaptation strategies.

Reservoir routing has been a routine procedure in hydrology, hydraulics and water management. It is typically based on the mass balance (continuity equation) and a conceptual equation relating storage and outflow. If the latter is linear, then there exists an analytical solution of the resulting differential equation, which can directly be utilized to find the outflow from known inflow, and to obtain macroscopic characteristics of the process, such as response and residence times, and their distribution functions. Here we streamline the reservoir routing framework and extend it to find approximate solutions for nonlinear cases. The proposed framework can also be useful for climatic tasks, such as describing the mass balance of atmospheric carbon dioxide and determining characteristic residence times, which have been an issue of controversy. Application of the theoretical framework results in excellent agreement with real world data. In this manner, we easily quantify the atmospheric carbon exchanges, and obtain reliable and intuitive results, without the need to resort to complex climate models. The mean residence time of atmospheric carbon dioxide turns out to be no more than four years and the response time is smaller than that, thus opposing the much longer mainstream estimates.

Using a detailed atmospheric radiative transfer model, we derive macroscopic relationships of downwelling and outgoing longwave radiation, useful for hydrological practice. We validate them using empirical formulae based on downwelling radiation data, which are in common use in hydrology, as well as satellite data for the outgoing radiation. We use the macroscopic relationships to infer the relative importance of carbon dioxide and water vapour in the greenhouse effect. The results show that the contribution of the former is 4% – 5%, while water and clouds dominate with a contribution of 87% – 95%. The minor effect of carbon dioxide is also confirmed by the small, non-discernible effect of the recent escalation of atmospheric CO2 concentration from 300 to 420 ppm, which is quantified at 0.5% for both downwelling and outgoing radiation. Water and clouds also perform other important functions in climate, such as regulating the heat storage and the albedo, as well as cooling the Earth’s surface though latent heat transfer, with a contribution of 50%. By confirming the major role of water on climate, these results suggest that hydrology should have a more prominent and more active role in climate research.

The impact of antecedent soil moisture content on soil erosion is a complicated phenomenon, which is still under argument with contradictions in research results. Hence, the objective of this study is to investigate the impact of antecedent soil moisture content to soil loss on clay soil by conducting two-year field experiments under natural rainfall on runoff plots with length of 10 meters, width of 3 meters, and uniform slope of 9%. Volumetric soil moisture sensors were used to log soil moisture changes, and soil moisture readings were used along with rainfall records to quantify the antecedent soil moisture conditions for each rainfall event. Results of this study show duration of the effective erosion event outranks the antecedent volumetric soil moisture content. Field study also suggests that accumulative rain falling within 48 hours (Pp48) prior to an effective erosion event strongly correlated with soil loss per Rainfall-Runoff Erosivity Index (Soil Loss / EI30), particularly when the duration of an effective erosion event is either between 3 ~ 7 hours or 10~ 30 hours. Hence, Pp48 can be considered as an alternative to replace antecedent soil moisture content in RUSLE 2’s cover and management factor.

Detecting and monitoring changes in soil salinity through remote sensing provides an opportunity for field assessment in regions where on-site measurements are limited. This investigation, carried out in Siwa Oasis, Egypt, aimed to assess the efficacy of several soil salinity indices derived from Landsat 5 and 7 satellite images. To achieve this, 56 on-site ground measurements were utilized for evaluation purposes. The study aimed to improve the correlation between EC and index values and explore the relationship between salinity and changes in land cover. Eleven spectral indices were calculated for nine scenes captured in different months from August to December. The first approach involved stacking the data to identify the index with the strongest correlation with ground EC values, without the need for complex analysis or EC value ranging. In the second approach, the ground EC measurements were classified into seven different salinity categories, and the correlation coefficient was calculated between each index and each salinity category. The third approach analyzed the data temporally, considering different salinity levels. Lastly, a spatial correlation analysis was conducted between EC and index values in the fourth scenario. The initial approach revealed a weak correlation due to substantial variation in EC values. However, the SI index demonstrated the highest correlation coefficient of 0.38. In the second scenario, the S2 index exhibited the highest correlation of 0.96 for moderate salinity samples. The third scenario showed that the S1 index achieved the highest correlation value of 0.99 for moderately saline areas. In the fourth scenario, the SI index exhibited the strongest correlation among all four ponds with correlation coefficients of 0.23, 0.23, 0.18, and 0.61. Notably, the correlations observed in the second and third scenarios demonstrated higher correlation coefficients compared to both the first and fourth scenarios. The study highlighted significant variations in EC levels related to land cover types and pond elevation. Additionally, remote sensing methods detected a 48% increase in total vegetated area over 17 years, showing the potential of remote sensing techniques in salinity monitoring for expanding agriculture and improving land management.

The escalation of mining activities in the karst regions of Guizhou Province has heightened the occurrence of water-inrush incidents in deep coal mines. This study focused on water-inrush phenomena within the Xinhua mining area of Jinsha County, Guizhou Province, aiming to investigate the sources of these incidents. The findings indicated that the overlying limestone of the Changxing Formation in the coal seam served as a vulnerable aquifer under certain conditions, leading to water inrushes. The analysis of the spatiotemporal distribution patterns of water-inrush incidents at the working face indicated that previous mining operations damaged the shallow Changxing Formation limestone, resulting in the accumulation of goaf water and the formation of numerous mining-induced fractures. These fractures served as rapid conduits for water inrushes from both atmospheric precipitation and underground sources at the deep working face. The examination of surface water and mine water quality demonstrated that both exhibited similar characteristics, predominantly featuring bicarbonate, sulfate, and sodium compositions. Investigation into the relationship between mine water inflow and atmospheric precipitation established that atmospheric precipitation influenced the mine water supply cycle, with a replenishment period of ~10 months during the operational phase of the Jinyuan Coal Mine and about one month post-closure. The fractures induced by mining activities within the Changxing Formation limestone facilitated water flow, with atmospheric precipitation serving as the primary water source for the mine. This study offered a valuable scientific foundation for addressing water-related damage resulting from atmospheric precipitation in mines susceptible to water inrushes under analogous hydrogeological conditions.

This study examines the environmental challenges faced by Malaysian industries in adhering to industrial effluent regulations with the research question, what are the challenges in complying with environmental legislations from industries? It investigates the primary factors contributing to non-compliance and the perspectives, knowledge, and needs of Malaysian industries regarding environmental compliance. This study recommends the best strategy for promoting self-compliance. Thirteen stakeholders from various industries with environmental management experience were interviewed. Over the past seven years, these industries have shown low com-pliance with the Industrial Effluent Regulation 2009, prompting an exploration of their adaptability to regulations. Challenges identified include cost, employee attitudes, technology, management support, public complaints, and jurisdictional issues. Responses varied from divergent to unified viewpoints, highlighting the complexity of compliance issues. Respondents suggested enhancing compliance through behavioral changes, including incentives, enforcement, awareness, guidance, industry ratings, management commitment, and public disclosure of emissions. Suggestions for improvement and innovative solutions emerged based on participants' experiences, emphasizing the importance of continuous improvement. The study emphasizes the government's crucial role in ensuring regulation adherence but underscores the need for analyzing barriers and exploring alternative approaches. Understanding industry perspectives and strategies is essential for progress. Compliance, however, requires an analysis of the current challenges and adopting adaptive measures. It is important to understand industries' perspectives and strategies to move forward.

EphB2 is a member of the Eph family tyrosine kinase receptors. EphB2 binds to ephrin-B1, ephrin-B2, and ephrin-B3, which are critical regulators of vascular and nervous development through controlling cell migration and axon guidance. EphB2 is overexpressed in tumors, including glioma, breast cancer, hepatocellular carcinoma, and malignant mesothelioma, and it functions as a tumor promoter. Therefore, the development of monoclonal antibodies (mAbs) against EphB2 is essential for tumor diagnosis and therapy for EphB2-positive tumors. In this study, we developed novel mAbs for human EphB2 using the Cell-Based Immunization and Screening (CBIS) method. One of the established anti-EphB2 mAbs, Eb2Mab-3 (mouse IgG1, kappa), reacted with EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and an endogenously EphB2-expressing cancer cell line (LS174T) by flow cytometry. Using flow cytometry, the dissociation constant (KD) values of Eb2Mab-3 for CHO/EphB2 and LS174T were determined as 1.1 × 10−9 M and 3.6 × 10−10 M, respectively. These results indicated that Eb2Mab-3 possesses a high affinity for detecting EphB2 and could apply to tumor therapy.

Accurate and reliable mid-long runoff prediction (MLTRP) is of great importance in water re-sources management. However the MLTRP is not suitable in each basin and how to evaluate the applicability of MLTRP is still a question. Therefore, the total mutual information (TMI) index is developed in this study based on the predictor selection method using mutual information (MI) and partial MI (PMI). The relationship between the TMI and the predictive performance of five models is analyzed by applying five models in 222 forecasting scenarios in Australia. The results over 222 forecasting scenarios demonstrate that, compared with the MI, the developed TMI index can better represent the available information in the predictors, and has more significant negative correlation with the RRMSE with the correlation coefficient between -0.62 and -0.85. This means the model's predictive performance will become better along with the increase of TMI, and there-fore the developed TMI index can be used to evaluate the applicability of MLTRP. When TMI is more than 0.1, the available information in the predictors can support the construction of MLTRP models. In addition, the TMI is used to partly explain the difference of predictive performance among five models. In general, the complex models, which can better utilize the contained infor-mation, are more sensitive to the TMI, and have more significant improvement in terms of predic-tive performance along with the increase of TMI. This research can provide support for the study of MLTRP.

The effects of CO₂-water-rock interactions on the mechanical properties of shale are essential for estimating the possibility of sequestrating CO₂ in shale reservoirs. In this study, uniaxial compressive strength (UCS) tests together with an acoustic emission (AE) system and SEM & EDS analysis were performed to investigate the mechanical properties and microstructural changes of black shales with different saturation times (10 days, 20 days and 30 days) in water dissoluted with sub-/super-critical CO₂. According to the experimental results, the values of UCS, Young’s modulus and brittleness index decrease gradually with increasing saturation time in water with sub-/super-critical CO₂. Compared to intact samples, 30-days’ saturation causes reductions of 56.43% in UCS and 54.21% in Young’s modulus for sub-critical saturated samples, and 66.05% in UCS and 56.32% in Young’s modulus for super-critical saturated samples, respectively. The brittleness index also decreases drastically from 84.3% for intact samples to 50.9% for samples saturated in water with sub-critical CO₂, to 47.9% for samples saturated in water with super-critical carbon dioxide (SC-CO₂). SC-CO₂ causes a greater reduction of shale’s mechanical properties. The crack propagation results obtained from the AE system show that longer saturation time produces higher peak cumulative AE energy. SEM images show that many pores occur when shale samples are saturated in water with sub-/super-critical CO₂. The EDS results show that CO₂-water-rock interactions increase the percentages of C and Fe and decrease the percentages of Al and K on the surface of saturated samples when compared to intact samples.

Nanling Mountain region is a typical southern hilly region, which plays an important ecological and environmental protection role in China's overall land protection pattern. Based on the remote sensing image data of Longnan City in Nanling Mountain in 2013, 2018 and 2023, this paper interpreted the land use type and analyzed the land use transfer situation by using Land use transfer flow, and Land use transfer matrix. At the same time, based on the remote sensing Ecological index (RSEI) model, the ecological environment quality of Longnan City from 2013 to 2023 was retrieved. The temporal and spatial response model of ecological environment quality to land use transfer in Longnan City from 2013 to 2023 was discussed based on Spatial autocorrelation and Geographic detector. The results show that from 2013 to 2023, the decrease of forest land (16.23km²) and the increase of construction land (13.25km²) were the main land use transfer in Longnan City. The ecological environment index of Longnan City in 2013, 2018 and 2023 was 0.789, 0.917 and 0.872, respectively, showing a trend of "first rising and then decreasing". The ecological environment quality in the north of Longnan City was significantly lower than that in the south, and the poor ecological quality area appeared in and around the northern main urban area, showing a trend of "inward contraction". Forest land, garden land, grassland, cultivated land and water area have a positive impact on ecological environment quality, while traffic land, construction land and other land have a negative impact on ecological environment quality. The response of ecological environment quality to different land use transfer modes is related to the change of the overall ecological environment quality. The interaction between LUCC and other factors had a great impact on the evolution of ecological environment quality in Longnan City.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Abstract: Due to sever land degradation throughout Ethiopia, the government has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. However, most of the rivers in Ethiopia carry huge amount of sediment in rainy season and streams dried up in the dry period. Planned research was conducted on two paired micro-catchments Mt.Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were collected from 22/11/2020 to 8/11/2022 on both micro-catchments at their outlets and center respectively. Base flow separation was done using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software was employed for data analysis. Flow duration curve (FDC) for both watersheds were developed. The FDC indicated that the base flow from treated micro-catchment ishigher and sustained in the dry season while it is low and un-sustained in untreated micro-catchment. From statistical analysis, there is a significant difference in base flow enhancement between the treated and untreated micro-catchment (P<0.001). Hence, catchment treatment contributed to improve groundwater recharge and sustain base flow in the dry season by reduce surface runoff during rainy season.

An adequate representation of the water infiltration process in the soil allows improving the efficiency in application and the uniformity in surface irrigation. The Green and Ampt model has shown a good representation of the process, and researchers from the United States Department of Agriculture (USDA) determined the values of their parameters for soils of that country, which are shown in tables or through functional relationships and this information is used as reference in several parts of the world, although there is no certainty that they are representative of the soils in Mexico. In this study, the parameters of the Green & Ampt equation were determined and evaluated in some soils of agricultural importance in Mexico. The parameters were obtained in four ways: one of them applied a methodology adapted from Brooks and Corey to quantify the wetting front capillary pressure head and used an permeameter under constant hydraulic head to determine the saturated hydraulic conductivity, and the other three consisted in taking them from three studies reported by the USDA. The values of the parameters suggested in Mexico drastically underestimated the results with relative errors (RE) in a range of -49.0 to -94.0% and the most representative were those obtained with the methodology proposed in this research with RE of -15.0 to 6.0%.

This paper analyses the application of deep learning techniques for predicting wave overtopping events in port environments using sea state and weather forecasts as inputs. The study was conducted in the outer port of Punta Langosteira, A Coruña, Spain. A video recording infrastructure was installed to monitor overtopping events from 2015 to 2022, identifying 3709 overtopping events. The data collected was merged with actual and predicted data for the sea state and weather conditions during the overtopping events, creating three datasets. We used these datasets to create several machine learning models to predict whether an overtopping event would occur based on sea state and weather conditions. The final models achieved a high accuracy level during the training and testing stages: 0.81, 0.73, and 0.84 average accuracy during training and 0.67, 0.48, and 0.86 average accuracy during testing, respectively. The results of this study have significant implications for port safety and efficiency, as wave overtopping events can cause disruptions and potential damage. Using deep learning techniques for overtopping prediction can help port managers take preventative measures and optimize operations, ultimately improving safety and helping to minimize the economic impact that overtopping events have on the port's activities.

Accurately predicting drug-drug interactions (DDIs) is crucial for preventing adverse drug events in clinical settings. However, existing methodologies often rely on complex models built from diverse data sources, posing challenges in computational drug discovery. To address the need for precise computational methods in predicting unknown DDIs, this study introduces a novel Deep Neural Network (DNN)-based approach. By leveraging a wide range of drug-related information, including substructure, targets, side effects, pathways, and indications, our method calculates multiple drug similarities. These similarities are then synthesized using a nonlinear fusion method to extract high-level features. Subsequently, a tailored neural network is deployed for interaction prediction. Comparative evaluation against three prominent machine learning classifiers—Extreme Gradient Boosting (XGBoost), Adaptive Gradient Boosting (AdaBoost), and Light Gradient-Boosting Machine (LGBM)—using three benchmark datasets demonstrates the superior performance of DNN. It achieves outstanding accuracy, precision, recall, and F1-score metrics, all reaching 94.6% in cross-validation. Additionally, case studies involving numerous drug pairs confirm the reliability of DNN in accurately predicting unknown DDIs. These findings underscore DNN as a potent and reliable method for DDI prediction, with promising implications for drug discovery and healthcare applications.

The aim of the study was to test the significance of the EPT index in the water quality assessment of three types of water bodies in hilly and mountainous region of Serbia. The aquatic macroinvertebrate community was dominated by the group of insects, of which 95 taxa represent the EPT group. We compared the obtained values of biological indices used for the assessment of water quality according to the national legislation with the overall status assessment represented by the ecological quality classes (EQC). The results of the Spearman correlation test showed a negative correlation of EQC with the EPT index, BMWP score, H', total number of taxa and number of sensitive taxa, while a positive correlation was observed for the values of SI and Tubificinae %. The values of EQC and biological indices were subjected to principal component analysis (PCA). The results showed that the parameters that contributed most to the differences were the EPT index, the BMWP score and the number of sensitive taxa. The results indicate that the EPT index is an excellent indicator of changes in water quality and an important tool for the ecological categorization of water bodies in mountain regions.

We describe a selective and sensitive fluorescence platform for the detection of trinitrophenol (TNP) based on competitive host–guest recognition between pyridine-functionalized pillar[6]arene (PCP6) and probe (acridine orange, AO) that used PCP6-functionalized reduced graphene (PCP6-rGO) as the receptor. TNP is an electron-deficient and negative molecule which is captured by PCP6 via electrostatic interactions and π-π interactions. Therefore, a selective and sensitive fluorescence sensor for TNP detection is developed. It has a low detection limit of 0.0035 μM (S/N=3) and a wider linear response of 0.01−5.0 and 5.0−125.0 for TNP. The sensing platform is also used to test TNP in two water and soil samples with satisfying results. This suggests that this approach has potential applications for the determination of TNP.

Abstract: Severe land degradation is the principal environmental problem in Ethiopian highlands in the form of soil erosion, and soil fertility loss, which is caused by human intervention for food, shelter, and energy demands. Soil erosion contributes to the loss of precious soil and water resources which are the basis of agricultural production and provide numerous other eco-system services. The Ethiopian highlands are one of the most degraded regions in the world. To combat such problems, the government of Ethiopia has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. Mount Yewel is one of the highlands in Northeastern Ethiopia where intensive soil and water conserva-tion has been implemented. Despite the massive investment in soil and water conservation measures, most of the rivers in the highlands of Ethiopia carry huge amounts of sediment with high flood risks in the wet season and streams are dried up in the dry period. Nonetheless, the impact of soil and water conservation measures on flood reduction and dry season flow en-hancement has not yet been quantified and evaluated. This research was then conducted on paired micro-catchments of Mount Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were col-lected from 22/11/2020 to 8/11/2022 on paired micro-catchments of Mount Yewel at their outlets and centers respectively. Base flow separation was done from the stream hydrograph using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software were employed for data analysis. Flow duration curves (FDC) for both watersheds were developed to compare the stream flow patterns between treated and untreated micro-catchments of Mount Yewel. The FDC indi-cated that the base flow from treated micro-catchment is higher and sustained in the dry season while it is low and unsustained in untreated micro-catchment. From statistical analysis, there is a significant (P

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

To develop peptide drugs targeting integrin receptors, synthetic peptide ligands endowed with well-defined selective binding motifs are necessary. The snake venom KTS-containing disintegrins, that selectively block collagen α1β1 integrin, were used as lead compounds for the synthesis and structure-activity relationship of a series of linear peptides containing the KTS-pharmacophore and alternating natural amino acids and 3-aminobenzoic acid (MABA). To ensure a better stiffness and metabolic stability, one, two and three MABA residues, were introduced around the KTS pharmacophore motif. Molecular dynamics simulations have determined that the solution conformation of MABA peptide 4 is more compact, underwent larger conformational changes until convergence, and spent most of the time in a single cluster. The peptides’ binding affinity has been characterized by enzyme linked immunosorbent assay in which the most potent peptide 4 inhibited with IC50 of 324±8 µM and 550±45 µM the binding of GST-α1-A domain to collagen IV fragment CB3, and the cell adhesion to collagen IV using α1-overexpressor cells, respectively. Docking studies and MM-GBSA calculations confirmed that peptide 4 binds a smaller region of the integrin near the collagen- binding site and penetrated deeper into the binding site near Trp1. Peptide 4, inhibited tube formation by endothelial cell migration in the Matrigel angiogenesis in vitro assay. Peptide 4 was acutely tolerated by mice, showed stability in human serum, decreased tumor volume and angiogenesis, and significantly increased the survival of mice injected with B16 melanoma cells. These findings propose that MABA-peptide 4 can further serve as an α1β1-integrin antagonist lead compound for further drug-optimization in angiogenesis and cancer therapy.

In this work, the wetting and evaporation behaviour of non-polar solvent droplets on thin soluble coatings is investigated experimentally. The wetting process on spin coated polymer layers by the solvent is captured using shadowgraphy. Initial spontaneous dynamic wetting as well as later stages of wetting are recorded and evaluated. Furthermore, structures obtained by wetting and subsequent evaporation of solvents on polymer coatings are studied by confocal microscopy. The solubility of the substrate has been varied by using polymers with different molecular masses. We observe that initial spreading dynamics does not depend on the molar mass in the studied range. However, we find a strong influence of the molar mass on the late stage wetting dynamics and on the surface structure after solvent evaporation.

Increased soluble endoglin (sENG) were observed in human brain arteriovenous malformations (bAVMs), and overexpression of sENG with vascular endothelial growth factor (VEGF)-A induced dysplastic vessel formation in mouse brain. However, the underlying mechanism of sENG-induced vascular malformations is not clear. While evidence suggests the role of sENG as a pro-inflammatory modulator, increased microglial accumulation and inflammations were observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that sENG with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, there were increased microglial activation around dysplastic vessels with expression of NLRP3, inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs while it decreased IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to release angiogenic/inflammatory responses which may be involved in EC dysfunction. Our study suggests the contribution of microglia in the pathology of sENG-associated vascular malformations.

This work investigates the stability conditions for linear systems with time-varying delays via augmented Lyapunov-Krasovskii functional(LKF). Two types of augmented LKFs with cross terms in integral are suggested to improve the stability conditions for interval time-varying linear systems. Through this work, the compositions of the LKFs are considered to enhance the feasible region of stability criterion for linear systems. Mathematical tools such as Wirtinger-based integral inequality(WBII), zero equalities, reciprocally convex approach, and Finsler’s lemma are utilized to solve the problem of stability criteria. Two sufficient conditions are derived to guarantee the asymptotic stability of the systems using linear matrix inequality(LMI). First, asymptotic stability criteria are induced by constructing the new augmented LKFs in Theorem 1. And then simplified LKFs in Corollary 1 are proposed to show the effectiveness of Theorem 1. Second, asymmetric LKFs are shown to reduce the conservatism and the number of decision variables in Theorem 2. Finally, the advantages of the proposed criteria are verified by comparing maximum delay bounds in two examples. Two numerical examples show that the proposed Theorem 1 and 2 obtained less conservative results than existing outcomes. Also, Example 2 shows that the asymmetric LKF methods of Theorem 2 can provide larger delay bounds and fewer decision variables than Theorem 1’s in some specific systems.

The collection of photo shoots during the systematic monitoring activities is useful to witness the ecological role of marine phanerogams as hosts for a rich variety of organisms in coastal and transitional waters. Cymodocea nodosa is present in the Taranto seas. In the Mar Piccolo, it reached high covers in short times, up to 100%, due to the bettering of the environmental conditions. The most recent observations showed that it offers welcoming towards several vertebrates and invertebrates, native and non-indigenous, as well as to micro and macroalgae. The NPPR funded activities will make these observations more robust and structural.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

This essay reexamines molecular evidence supporting the existence of the ‘preisthmus’, a caudal midbrain domain present in vertebrates (studied here in the mouse). It is held to derive from the embryonic m2 mesomere and appears intercalated between the isthmus (caudally) and the inferior colliculus (rostrally). Among a substantial list of gene expression mappings examined out of the Allen Developing and Adult Brain Atlases, a number of quite consistent selective positive markers, plus some neatly negative markers were followed across embryonic stages E11.5, E13.5, E15.5, E18.5, and several postnatal stages up to the adult brain. Both alar and basal subdomains of this transverse territory were explored and illustrated. It is argued that the peculiar molecular and structural profile of the preisthmus is due to its position adjacent rostrally to the isthmic organizer, where high levels of both FGF8 and WNT1 morphogens must exist at early embryonic stages. Isthmic patterning of the midbrain is discussed in this context. Studies of the effects of the isthmic morphogens usually do not attend to the largely unknown preisthmic complex. The adult alar derivatives of the preisthmus were confirmed to comprise a specific preisthmic sector of the periaqueductal gray, an intermediate stratum represented by the classic cuneiform nucleus, and a superficial stratum containing the subbrachial nucleus. The basal derivatives, occupying a narrow retrorubral domain intercalated between the oculomotor and trochlear motor nuclei, include dopaminergic and serotonergic neurons, as well as a variety of peptidergic neuron types.

Hydrological processes are complex to compute on hilly areas when compared to the plain areas. Most of the hydrological model do not take into account the critical rainfall-runoff generation processes such as subsurface storm flow, saturation excess flow, overland flow, return flow and pipe storage. The simulations of the above processes in the soil matrix requires detailed hillslope hydrological modelling. In present study, a hillslope experimental plot is designed to study the runoff generation processes on the plot scale. The setup is designed keeping in view the natural hillslope conditions prevailing in the north western Himalayas, India where high intensity storm event occurs frequently. Using the experimental data and the developed conceptual model, the overland flow and the subsurface flow through macropore dominated area has been estimated/analyzed on the pixel basis. Over the experimental hillslope plot, a rainfall simulator was installed to generate the rainfall intensity in the range of 15 to 150 mm/hr which represented the dominating rainfall intensity range in the region. Soil moisture sensors were also installed at 100 mm and 300 mm depth at different locations of the plot to observe soil moisture variations. It was found that once the soil is saturated, it remains in the field capacity for next 24-36 hours. Such antecedent moisture conditions are most favorable for the generation of rapid stormflow from hillslopes. Dye infiltration test was also performed on the undisturbed soil column to observe the macropore fraction variability over the vegetated hillslopes. The surface runoff predicted using the developed hillslope hydrological model compared well with the observed surface runoff under high intensity rainfall conditions.