2019-n-CoV is the seventh coronavirus known to infect humans and cause serious illness, and due to its lethality there was a worldwide mobilization for the development of new drugs and new vaccines for Covid-19. Therefore, the present work aims to carry out a virtual screening of terpenes with potential anti SARS-CoV-2 activity. To perform the ligand-based virtual, a model was constructed regarding the compounds which already showed inhibitory activity of the SARS-CoV-2. The test series corresponded to terpenes isolated in the Fabaceae Family. The compounds that were most likely to activity were subjected to Molecular Docking and the best poses obtained were subjected to Molecular Dynamics (MD) simulations carried. The molecules under study were submitted to in vitro evaluation to assess inhibitory activity of compounds against SARS-CoV-2 in a phenotypic screening model of the virus. The compounds selected by in silico screening corresponded to triterpenoids from the lupane series. In the in vitro test, both demonstrated activity against the SARS-CoV-2 virus. The virtual screening performed managed to identify the compounds with the highest probability of activity, as well as the most stable compounds, and the method used was validated by the in vitro study carried out.

Strategic intelligence covers the examination of what impacts and influences the business and the related SWOT analysis, (strengths, weaknesses, opportunities, and threats mapping). Through this research, leaders will be able to properly allocate and re-route resources, identify areas of improvement, and ensure that strategic initiatives are aligned with the organization's mission. Strategic intelligence is, therefore, effective through the use of critical thought and data-driven decisions and seeing the outcomes of different positioned alternatives. It must also form and support a culture of cooperation and open communication within the organizations, stimulating employees' inputs and learning curves. The article's subject is the necessity for strategic intelligence, a crucial competence for leaders, managers, and companies striving to remain competitive, to be utilized and best leveraged in today's volatile and dynamic business contexts. It helps the leadership turn proactive, foresee trends, and make correct, agile decisions that enforce companies' long-term growth and success. This study follows a research design that includes a thorough literature review and bibliometric research, executed via VoSViewer, illustrating the concept of strategic intelligence from a leadership point of view as a driver of competitive advantage. Further, the article points out that the limitations are acknowledged because the literature on the matter is limited, as strategic intelligence is relatively new to the business sector; moreover, more research is required to fully understand and use the potential of strategic intelligence in business growth. By overcoming these limitations and continuing to study this concept, businesses can gain a competitive edge and make informed decisions that fuel their success in an ever-evolving market. As a result, this study contributes to developing strategic intelligence in leadership and business and paves the road for further research and applications of strategic intelligence theories in organizational contexts.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

Abstract: Efforts for carbon emission reduction have been identified as a major climate change mitigation target in the Paris Agreement. The 26th Conference of Parties to the United Nations Framework Convention on Climate Change highlighted the worldwide effort for cleaner and greener mining, urging the mineral industry to embrace greener operational emissions reduction technologies and strategies. Ghana pledged at the Paris Conference to reduce CO2 emissions by 15% and increase renewable energy share to 10% of the national energy mix. Here the fundamental question is how Ghana’s mining industry can contribute to CO2 emission reduction efforts. This paper investigates barriers to low-carbon emission policy implementation among mining companies in Ghana. The questionnaire survey was conducted among Ghana’s four large-scale gold mining companies. As the sample number of available companies is limited, we used a descriptive analysis to assess the responses. The results show that the companies expressed widely different ways to respond to the issues of cost, a government policy/regulations for carbon emission reduction, and the adoption/acquisition of low-carbon technologies. Those companies that are relatively less prepared for this endeavor emphasized the uncertainties of securing sufficient energy in case of using low-carbon technologies. They also expressed a need for more trained workers to handle low-carbon technologies. All companies agreed with a expected high cost of adopting low-carbon options. There was a communication gap with the relevant government ministry about low-carbon mining options where the government should be able to facilitate the involvement of othe low technology providers, such as solar PV installation.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

This manuscript presents a new two-parameter unit stochastic distribution, obtained by transforming the Laplace distribution, using generalized logistic map, into a unit interval. The distribution thus obtained is named the Laplace-logistic unit (abbreviated LLU) distribution, and its basic stochastic properties are examined in detail. Also, the procedure for estimating parameters based on quantiles is provided, along with the asymptotic properties of the obtained estimates and the appropriate numerical simulation study. Finally, the application of the LLU distribution in dynamic and regression analysis of real-world data with accentuated "peaks" and "fat" tails is also discussed.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Seventy-seven percent of Irish primary school children do not meet recommended physical activity (PA) guidelines [1]. The Daily Mile (TDM) is a primary school initiative designed to increase children’s PA output. This study evaluates TDM’s perceived effect on Irish primary school children’s health-related metrics. A mixed-methods study, comprising two data collection phases, used the RE-AIM framework to evaluate TDM [2]. Phase one involved teachers, principals and classroom assistants (n = 191) from TDM-registered schools completing a questionnaire. Two TDM-registered schools participated in phase two where, (i) interviews were conducted with each principal, (ii) a teacher sub-sample (n = 4) participated in a focus group and (iii) a child sub-sample (n = 14) participated in separate focus groups. TDM was perceived to positively impact markers of children’s health, including their PA behaviour, physical fitness and social wellbeing. Inclement weather (66.5%) and a lack of time (56.5%) were reported as the top-ranked implementation barriers. Moreover, TDM’s repetitive nature often left children feeling disinterested and resulted in some teachers modifying the initiative to maintain engagement levels. Maintaining the long-term implementation of TDM and its health benefits in primary schools may require bespoke amendments to the original format to preserve children’s engagement.

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 mechanisms underlying the establishment of asymmetric structures during development remain elusive. The wing of Drosophila is asymmetric along the Anterior-Posterior (AP) axis, despite that its growth signals that drive its growth are presumably symmetric. Here, we investigated the contribution of cell recruitment, a process that drives wing fate differentiation in Drosophila, to the asymmetric shape and pattern of the adult wing. Genetic impairment of cell recruitment results in a significant reduction in adult wing asymmetry, primarily affecting the region between longitudinal vein 5 and the wing margin (L5-M). Morphometric analysis reveals that the lack of cell recruitment results in a more symmetric wing with respect to the AP, suggesting a contribution of cell recruitment to the establishment of asymmetry in the adult wing. A close examination of the expression of the wing selector gene vestigial (vg) in wing disc does not support this hypothesis. However, the circularity of the Vg pattern significantly increase in recruitment-impaired wing disc, suggesting that while the decrease of the L5-M region in the adult wing may not be attributed to cell recruitment, it could contribute to the overall asymmetry of the adult wing. We conclude that cell recruitment, a widespread mechanism that participates in growth and patterning of several developing systems, could drive, at least partially, the asymmetric shape of the Drosophila wing.

Tuberculosis (TB) continues to pose a global health challenge, exacerbated by the rise of drug-resistant strains. The development of new TB therapies is an arduous and time-consuming process. To expedite the discovery of effective treatments, computational structure-based drug re-purposing has emerged as a promising strategy. From this perspective, conditionally essential targets present a valuable opportunity, and the mycobactin biosynthesis pathway stands out as a prime example highlighting the intricate response of Mycobacterium tuberculosis (Mtb) to changes in iron availability. This study focuses on the re-purposing and revival of FDA-approved drugs (library) as potential inhibitors of MbtA, a crucial enzyme in mycobactin biosynthesis in Mtb conserved among all species of mycobacteria. Literature suggests this pathway to be associated with drug efflux pumps, which potentially contribute to drug resistance. This makes it a potential target for antitubercular drug discovery. Herein we utilized cheminformatics and structure-based drug repurposing approaches, viz., molecular docking, dynamics, and PCA analysis, to decode the intermolecular interactions and binding affinity of the FDA-reported molecules against MbtA. The virtual screening revealed ten molecules with significant binding affinities and interactions with MbtA. These drugs, originally designed for different therapeutic indications (4: antiviral, 3: anticancer, 1: CYP450 inhibitor, 1: ACE inhibitor, and 1: leukotriene antagonist), are repurposed as potential MbtA inhibitors. Furthermore, our study explores the binding modes and interactions between these drugs and MbtA, shedding light on the structural basis of their inhibitory potential. Principal component analysis highlighted significant motions in MbtA-bound ligands, emphasizing the stability of the top Protein-Ligand Complexes (PLCs). This computational approach provides a swift and cost-effective method for identifying new MbtA inhibitors, which can subsequently undergo validation through experimental assays. This streamlined process is facilitated by the fact that these compounds are already FDA-approved and have established safety and efficacy profiles. This study has the potential to lay the groundwork for addressing the urgent global health challenge at hand, specifically in the context of combating Antimicrobial Resistance (AMR) and Tuberculosis (TB).

The maneuverability of ships is influenced by several factors, including ship design, size, propulsion system, hull shape, and external conditions such as wind, waves, and currents. The size, shape, and arrangement of the hull, rudder, and propeller are decisive for maneuverability. Hydrodynamic forces such as bank effect and squat significantly impact the maneuverability of large ships in narrow channels. With the increasing trend of building ever-larger ships, the demand to evaluate the maneuvering performance of the ship at the design stage has become more critical than ever. Both experimental and computational methods are used to obtain accurate maneuvering characteristics of vessels. In this study, the methods for predicting ship maneuvering characteristics are analyzed using a systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA). This article contributes to a deeper understanding of the hydrodynamic capabilities of ships and identifies possible future challenges in the field of ship hydrodynamics. The findings inform educators and the shipping industry about the importance of predicting the maneuvering performance of ships, with an emphasis on the education and training of seafarers needed to make timely decisions in critical situations.

The environmental Kuznets curve (EKC) hypothesis posits an inverted U-shaped relationship between economic growth and environmental degradation. However, there is no consensus regarding the EKC hypothesis among countries and regions of different income groups. In this study, we analyze the EKC hypothesis for 158 countries and 44 regions from 1990 to 2020, categorizing them into different income groups based on the World Bank's income classification (low, lower-middle, upper-middle, and high-income countries). Our findings reveal mixed patterns in the EKC across different income levels, highlighting the heterogeneous relationship between economic growth and carbon emissions and showing differentiated patterns among different income levels. While a rise in income for high-income countries should be reflected in a shift toward fewer carbon emissions, for lower-income countries, growth is still associated with rising emissions. This underscores the urgent need for policy interventions that decouple economic development from environmental degradation. A balanced approach to economic growth, which prioritizes carbon neutrality across all stages of development, by tailoring environmental and economic strategies to address CO2 emissions effectively, should be adopted, recognizing the different developmental stages and income levels of countries and regions.

Reducing the levels of toxic chemicals that cause adverse health and environmental impacts is a challenge for the international community. There is a need of a global strategy. Indeed, too often the problems associated to the exposure of chemical substances is recognized a posteriori, in the presence of consequences already observed. The prediction of the likely effects of chemical exposure on human health is based on classical tests with animals, which are time and money consuming, may deviate from an accurate prediction towards humans, and arises ethical concerns. Regulations are now considering the adoption of in silico (or computational) methods, which can be used for prioritizing substances according to the probability to be toxic for the biosphere. Several initiatives have prioritized chemicals, typically based according to some criteria, such as chemicals which may be endocrine disruptors, or persistent, bioaccumulative, or toxic (PBT). However, these initiatives focused on a certain range of adverse properties, and covered a certain number of substances only. We applied a set of largely validated and widely used predictive methods to large collections of chemicals: (i) to about 340,000 with a defined function, and (ii) to about 6 millions, which have been synthetized. The aim of this study is to quantify the putative impact of existing and future chemicals on towards human health, ecological and environment properties. The impact on the environment is the cause of major concern. This is the case of pesticides and hazardous, which is quite expected; however, also pharmacologically active candidate compounds of natural origin may have a high level of ecotoxicity. Pesticides and hazardous are also the categories of higher concern for humans, followed by pharmaceuticals. The pesticides and the hazardous are the categories of higher concern also on the environmental point of view. The results of our analysis could be the basis for the identification of new safety rules.

In this paper, we introduce the notion of the generalized $w$-group inverse in a Banach algebra with proper involution. This is a natural generalization of generalized (weak) group inverse in Banach *-algebras. Many elementary properties of such new weighted generalized inverse are presented. We further establish the equivalent relations between generalized weighted group inverse and weighted generalized Drazin inverse. Related properties of generalized (weak) group inverse are extended to the wider cases.

This study explored the intricate nexus between public service provision and land use planning, with a specific focus on the conservation of local plant species in Tambon Khao Phanom, Amphoe Khao Phanom, Krabi Province. Rooted in commitment. The research framework encompasses three fundamental activities: resource survey and collection, resource conservation and utilization, and resource development planning for public services, emphasizing land use planning for local plant species conservation. This multidisciplinary approach integrates the one-map method and draws data from the Department of Land Development to formulate a comprehensive land utilization plan that optimizes land use for biodiversity conservation. This study underscores the critical synergy between public service delivery and land use planning, highlighting their collective potential to advance community well-being and sustainable development.

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 study of the concentrations and effects of fine particulate matter in urban areas have been of great interest to researchers in recent times. This is due to the acknowledgment of the far-reaching impacts of fine particulate matter on public health. Remote sensing data have been used to monitor the trend of concentrations of particulate matter by deriving aerosol optical depth (AOD) from satellite images. The Center for International Earth Science Information Network (CIESIN) has released the second version of its global PM_2.5 data with improvement in spatial resolution. This paper revisits the study of spatial and temporal variations in particulate matter in Saudi Arabia by exploring the cluster analysis of the new data. Cluster analysis of the PM_2.5 values of Saudi cities is performed by using Anselin local Moran’s I statistic. Also, the analysis is carried out at the regional level by using self-organizing map (SOM). The results show an increasing trend in the concentrations of particulate matter in Saudi Arabia, especially in some selected urban areas. The eastern and south-western parts of the Kingdom have significantly clustering high values. Some of the PM2.5 values have passed the threshold indicated by the World Health Organization (WHO) standard and targets posing health risks to Saudi urban population.

Subnational governments play a key role responding to climate change risks in terms of policy strategies and instruments. This article analyzes how Brazilian municipal and state governments have developed and implemented public policies to mitigate and to adapt to climate change risks. We surveyed all cities’ and states’ climate policies within the country. The methodological approach includes five main points of analysis: 1. mitigation targets and intentions; 2. adaptation actions; 3. stakeholders’ participation; 4. policy implementation; 5. participation in networks related to climate change. Our results suggest that even though subnational climate policies in Brazil are isolated initiatives within the national context, they play an important role responding to climate change risks in different scales and levels. The strongest Brazilian policies with both mitigation and adaptation actions counted on previous mobilization for the climate issue involving different stakeholders from several segments of the society. These governments have also participated in transnational cooperation networks related to climate change.

The olive tree (Olea europaea L.) is an evergreen tree that occupies 19% of the woody crop area and is cultivated in 67 countries on five continents. The largest olive production is concentrated in the Mediterranean basin, where the olive tree has had an enormous economic, cultural and environmental impact since the 7th century BC. In the Mediterranean region, salinity stands out as one of the main abiotic stress factors significantly affecting agricultural production. Moreover, climate change is expected to lead to increased salinisation in this region, threatening olive productivity. Salt stress causes combined damage by osmotic stress and ionic toxicity, restricting olive growth and interfering with multiple metabolic processes. A large variability in salinity tolerance among olive cultivars has been described. This paper aims to synthesize information from the published literature on olive adaptations to salt stress and its importance in salinity tolerance. The morphological, physiological, biochemical, and molecular mechanisms of olive tolerance to salt stress are reviewed.

REDD+ (Reducing Emissions from Deforestation and Forest Degradation) aims to achieve its purpose by working across multiple sectors and involving multi-level actors in reducing deforestation and forest degradation in tropical countries. By contrast, the European Union (EU) Action Plan on Forest Law Enforcement, Governance and Trade (FLEGT) and its Voluntary Partnership Agreements (VPAs) focus on forestry and functions at bilateral state level. The FLEGT Action Plan specifically aims to tackle illegal logging, legalise timber production and trade improve forest governance in countries exporting tropical timber to the EU. Since illegal logging is just one driver of deforestation and forest degeneration, and legalisation of logging does not necessarily reduce deforestation and forest degradation, the two instruments differ in scale and scope. However, by addressing the causes of deforestation and forest degradation and their underlying governance issues, the EU FLEGT and REDD+ share many functional linkages at higher levels of forest policy and forest governance. The contribution and participation of civil society organisations (CSOs) and other actors is imperative to both processes. Our study is based on a survey of key actors (national and international) in REDD+ and FLEGT VPA processes in the Lao People’s Democratic Republic. Our analysis was guided by the theoretical perspectives of the policy arrangement approach and examination of two specific dimensions of this approach, namely resources and rules of the game. This paper argues that participation of CSOs in both processes is crucial as it facilitates and nurtures the very much needed cooperation between other national and international actors. The paper also argues that participation of CSOs feeds valuable information and knowledge into REDD+ and FLEGT VPA processes, thus contributing to increased legitimacy, justice and transparency.

In the past few years, cloud-based additive manufacturing has shown its application and potential in industries. For this reason, when the demand for cloud-based additive products increases, efficient scheduling of related tasks becomes more important to achieve optimized duration. This research proposes a Heuristic Scheduling Algorithm (HSA) for use in Cloud-Based Additive Manufacturing (CBAM) with an approach to Critical Chain Buffer Management (CC/BM). This research aims to schedule and optimize the time in cloud-based additive manufacturing, in addition to the parts production process, it also includes the steps of receiving online orders and informing the manufacturing unit and sending them to the customer. The HSA proposed in this research consists of three phases 1- Buffer sizing, 2- Additive manufacturing and logistics scheduling, and 3- Buffer controlling. To evaluate, the performance of the algorithm is simulated. The finding shows that the proposed HAS can effectively solve the CBAM scheduling problem.

Abstract: Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed.

Quite a number of cottonseed varieties are existed. The seeds of each variety produce a different amount of gossypol as a natural toxic compound. The increased interest in this natural product and its toxic effects were enhanced the demand for establishing simple silica-gel-based methods for its isolation, purification, and characterization. Historically, silica gel plays a significant role in isolation and purification of many different natural products. Silica gel is variants and can intro-duce a lab, simple tool for tracking a compound in certain plants during its purification process. In this study, gossypol was isolated and purified in the form of yellow crystals as gossypol acetic ac-id. Several methods and tools were used for its characterization including TLC, preparative TLC, silica gel column, UV/IR spectrophotometer and HPLC (Robust spherical silica gel). A compara-tive study between its amounts in both Egyptian and Chinese varieties were performed. Under the experimental condition, the Egyptian cottonseeds contain 8.705 gm/kg, while the Chinese contains 5.395 gm/kg. Thin Layer Chromatography (TLC) had been flourished the science of the phytochemistry and still popular till nowadays and is recommended for fast, accurate, and inex-pensive evaluation and quantification of gossypol. It is recommended to isolate and purify gossy-pol as gossypol acetic acid using optimized combined methods used in this study. Using Silica gel different protocols will assist and facilitate the parallel comparison and save the compact column from any unexpected contaminants during the purification steps. During each step the silica gel itself could be simply removed by paper filtration.

Norepinephrine (NE) uptake through the NE transporter (NET) is the primary mechanism to ter-minate the action of this neurotransmitter. Dysregulation of brain NE levels is associated with various conditions, including attention deficits, depression, and Alzheimer's disease. Recently, we identified an interaction between the related dopamine (DA) transporter (DAT) and G protein βγ subunits. Activation of Gβγ in cells and brain slices leads to DA efflux through DAT. However, the potential interaction between Gβγ and NET has not been reported. Here, we used a combina-tion of molecular modeling approaches to elucidate the structural details of the NET/Gβγ inter-action, supported by experimental evidence. Through 1.5µs of molecular dynamic simulation, we observed a favorable NET/Gβγ interaction mediated by the intracellular carboxy terminus of NET. As a consequence, the binding energy of NE for NET also changes resulting in alterations of the electrostatic profile of NET. We propose that these changes mediate the NE efflux effect. Fi-nally, we provide experimental evidence demonstrating that Gβγ physically interacts with NET and that the Gβγ activator mSIRK induces NE efflux through the transporter. These findings identified a novel interaction between Gβγ and NET and highlighted its potential implications in the regulation of NE neurotransmission and associated disorders.

The eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate 1, with promising insecticidal capability was encapsulated in liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and of 100% dioleoylphosphatidylglycerol (DOPG). Compound-loaded Egg-PC:Ch liposomes exhibit small hydrodynamic diameters (below 100 nm), high encapsulation efficiency (88.8% ± 2.7%), higher stability and a more efficient compound release, being chosen for assays in Sf9 insect cells. Compound 1 elicited a loss of cell viability up to 80% after 72h of incubation. Relevantly, encapsulation maintained the toxicity of compound 1 towards insect cells, while it lowered toxicity towards human cells, thus showing the selectivity of the system. Structure based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase.

Driven by the growing interest of the scientific community and the proliferation of research in this field, cranial implants have seen significant advancements in recent years regarding design techniques, structural optimisation, appropriate material selection and fixation system method. Custom implants not only enhance aesthetics and functionality but are also crucial for achieving proper biological integration and optimal blood irrigation, critical aspects in bone regeneration and tissue health. This research aims to optimize the properties of implants designed from triply periodic minimal surface structures. The gyroid architecture is employed for its balance between mechanical and biological properties. Experimental samples were designed varying three parameters of the surface model: cell size, isovalue and shape factor. Computational simulation tools were used for determining the relationship between those parameters and the response variables: the surface area, permeability, porosity and Young modulus. These tools include computer aided design, finite element method and computational fluid dynamics. With the simulated values, the corresponding regression models were fitted. Using the NSGA-II, a multi-objective optimisation was carried out, finding the Pareto set which includes surface area and permeability as targets, and fulfil the constraints related with the porosity and Young modulus. From these non-dominated solutions, the most convenient for a given application was chosen, and an optimal implant was designed, from a patient computed tomography scan. An implant prototype was additively manufactured for validating the proposed approach.

As part of valorisation of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a-v bearing 1,2,3-triazole moieties were designed and synthesized by treating a previously azide 4 prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues 18a-v were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes; and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained notably against L. monocytogenes. Compounds 18d, 18g and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. Molecular docking study was performed to explore the binding mode of the most active derivatives against the target protein from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor to the experimental data.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

Areas covered with vegetation play a key role for life on Earth and should be inventoried in a clear and complete manner in order to improve the process of its protection and development. Data showing the amount of greenery in areas most deformed by humans, i.e. urbanized areas, are particularly important. Local governments need to know how to invest theirs limited sources in the quality of life of residents by supplementing the urban fabric with additional vegetation. The article presents a proposal for how to calculate the degree of greenness of cities based on remote sensing data. Additionally, a novel method was proposed to help in planning the development of areas covered with vegetation, taking into account the spatial distribution of the local population. The result was a comprehensive method presenting the actual natural situation in a specific city.

Endophytic fungi are those that present part of their life cycle in healthy tissues of different plant hosts in symbiosis without causing harm. At the same time, fungus-plant symbiosis makes it possible for microorganisms to synthesize their own bioactive secondary metabolites while in stationary stage. Such microorganism-derived secondary metabolites contribute. Therefore, this work aimed to. To accomplish this, the endophytic fungus Trichoderma asperellum was isolated from Bertholletia excelsa (Brazil nut) almonds. The fungus was cultivated and extracted with ethyl acetate, obtaining AM07Ac. Then, using HPTLC (High-performance thin-layer chromatography) and Nuclear Magnetic Resonance (1H NMR), β-amyrin, kaempferol, and brucine were identified as major compounds. Further in vivo assays in Zebrafish demonstrated the activity of AM07Ac on melanogenesis by producing a concentration-response inhibitory effect, which, through an in silico study, proved to be related to the noted major compounds known to inhibit tyrosinase activity. The inhibition of tyrosinase prevents melanin accumulation in skin. Therefore, these results imply the importance of investigating microorganisms and their pharmacological activities, in particular the endophytic fungus Trichoderma asperellum as a generator of active metabolites for melanogenesis modulation.

Vertical-axis wind turbines (VAWTs) are receiving more and more attention as they involve simple design, cope better with turbulence and are insensitive to wind direction which has a huge impact on the cost since the yaw mechanism is not needed. However, VAWTs still suffer from low conversion efficiency. As a results tremendous efforts are exerted to improve its efficiency which mainly focus on two methods regardless of whether the study is a CFD simulation or a field test or lab test experiment. An active approach which involves the modification of the rotor itself such as the blade design, angle, trailing and leading edges, inner blades, chord thickness, contra-rotating rotor, etc. While the second approach involves passive techniques where the flow is directed to optimally face the downwind rotor by mounting a guiding vane such as a diffuser or other shapes at the upwind position of the rotor. Among all techniques undertaken, the CRWT rotor technique seems to be the most effective with an output even comparable to that of Horizontal Axis Wind Turbines (HAWT), while the Savonius rotor received more attention compared to other designs of VAWTs. Apart from technological issues, it was also suggested that geographical issues such as proper site siting of the wind turbine rotor at a particular location where a uniform flow could be guaranteed is of paramount importance to ensure an effective conversion capacity of wind turbines.

Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network’s (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.

This paper aims to build up a preference function to evaluate the public benefits of the type of agricultural farming, biodiversity, water provisions, land use type, ecotourism modes, and a monetary attribute (environmental trust fund and willingness to contribute) associated with an ecosystem service and land use program in a forest park. This study used the choice experiments to build a random utility model, analyze the average preference for the above land use attributes based on the conditional logit and used a latent class model to test the resident’s heterogeneous preferences for land use planning in the forest park. We also estimated the welfare derived from various land use programs. The empirical result had shown that: (1) increasing organic farming area, maintaining the status quo of species biodiversity, increasing the surface water provision, increasing the area of custom flora, increasing the wetland area, and setting up an integrated framework for ecotourism increase the public’s preference for the land use program; (2) we found that farmer and non-farmer haven’t the same land use preferences; (3) the ecotourism development program incorporating biodiversity, organic farming, ethnobotany, and wetland area with integrated ecotourism are more preferred than other land use program scenarios.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

The permanent protection of groundwater and surface sources of drinking water in the required raw water quality from contamination is the primary foundation of preserving the life of society and the entire engineering infrastructure operability not only in the Czech Republic but also in other countries of the world. One of the basic ways of contamination prevention enhancement and risk mitigation of putting a water source out of operation is the identification of the given risk as well as soil contamination monitoring. The purpose of this study is to understand specific aspects of contamination threats to drinking water sources and determine possible solutions to eliminate the risk, shown in the example case study in the Czech Republic conditions. Based on the findings, a proposal to enhance the prevention of water source contamination has been elaborated in the form of recommendations regarding the ways and means used to monitor the risk areas and to implement technical measures so as to eliminate or terminate the specified risk. A complex approach based on the integration of interdisciplinary factors and methodology is required to minimize the threats of aquatic ecosystems contamination in the Czech Republic.

Risedronate sodium (RIS) possesses very low bioavailability and several adverse effects in the gastrointestinal tract when administered through an oral route. Thus, this necessitates the need to develop novel formulation. Hence, we had developed RIS-HA-TCS loaded mPEG coated nanoparticles for the treatment of osteoporosis. Chitosan was used to synthesize thiolated chitosan and its characterization was done using DSC and FTIR. Ellman's reagent was used to measure the degree of thiol immobilization. The RIS-HA fabrication was done and was further conjugated with the synthesized TCS. The Box-Behnken design process was used for designing fifteen batches of RIS-HA-TCS nanoparticles, which were formulated by ionic gelation procedure in which tripolyphosphate (TPP) was used as a crosslinking agent. Moreover, RIS and RIS-HA-TCS in-silico activity was compared for farnesyl pyrophosphate synthetase enzyme. The obtained results revealed that the binding affinity of RIS was much more than the conjugated RIS. Successful docking results paved the way for thiolation of chitosan with RIS. The drug entrapment efficiency (%EE), particle size and Polydispersity index (PDI) of RIS-HA-TCS nanoparticles obtained were 85.4 ±2.21%, 252.1 ±2.44 nm and 0.2± 0.01 respectively. The particle size, PDI, and encapsulation efficiency of RIS-HA-TCS were reported to be 264.9 ±1.91 nm, 0.120± 0.01, and 91.1 ±1.17%, respectively, after being further conjugated with mPEG. TEM showed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. The in-vitro release of RIS-HS-TCS-mPEG was found to be significantly higher (95.13±4.64%) as compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%) and marketed formulation (74.69 ± 3.98%). In an ex-vivo gut permeation study, RIS-HA-TCS-mPEG nanoparticles was found to have an apparent permeability of 0.5858×10-1 cm/min which was better than the apparent permeabilities of RIS-HA-TCS formulation (0.4011 ×10-4cm/min), RIS suspension (0.2005 ×10-4 cm/min) and marketed preparation (0.3401 ×10-4 cm/min)..

Given the opportunities offered by foreign investment in energy infrastructure mostly by Chinese firms, the Government of Cambodia is giving high priority to developing hydropower resources for reducing energy poverty and powering economic growth. Using a “Political ecology of the Asian drivers” framework, this paper assesses China’s involvement in the development of large dams’ in Cambodia and its impacts on the access of natural resources such as water and energy by dam builders, local communities and the government. This analysis is based on 61 interviews and 10 focus group discussions with affected communities, institutional actors, Chinese dam builders and financiers in relation to the first large Chinese dam built in Cambodia, the Kamchay dam. Based on the results of the analysis this paper makes recommendations on how to improve the planning, implementation and governance of large dams to ensure that the dams’ benefits are shared more equally.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Ghana Tamale's current waste management system is overwhelmed by the growing waste crisis, necessitating the exploration of Waste-to-Energy technologies as an innovative solution. This study explores challenges and opportunities for integrating Waste-to-Energy (WtE) technologies into Tamale's existing waste management system. Qualitative research identified policy hurdles, financial constraints, social concerns, and institutional weaknesses as key barriers. Conversely, stakeholder collaboration, public education, and capacity building emerged as some success fac-tors. A proposed implementation plan emphasizes feasibility studies, public engagement, pub-lic-private partnerships (PPPs), and technology selection based on waste composition. Addition-ally, a novel framework for WtE integration within a broader Integrated Solid Waste Manage-ment (ISWM) system is presented. This framework incorporates waste sorting, recycling, WtE alternatives, and responsible management of residuals. Validation by key stakeholders con-firmed the framework's potential to improve waste management in Tamale. By overcoming identified challenges and implementing the proposed framework, Tamale can achieve environ-mental sustainability, energy generation, and progress towards UN SDGs 7, 11, and 12. This re-search offers valuable insights for policymakers and paves the way for a cleaner and more sus-tainable future for Tamale, potentially serving as a model for other developing cities.

In today's intricate media landscape, the resilience and relevance of public service media (PSM) depend on their capacity to align with the diverse and evolving expectations of the public. However, the audience perspective is often overlooked, resulting in a limited understanding of public expectations. This study employs a bottom-up approach that allows for a re-evaluation of the expectations from the audience's viewpoint. It investigates the public's expectations for PSM, drawing on data from 10 focus group discussions (with 60 participants) conducted in the Czech Republic. The findings indicate that expectations can be categorized into four primary dimensions: (1) the expected roles and functions of PSM; (2) the general characteristics of the PSM content (defining the desired nature of PSM content); (3) the principles governing the functioning of PSM (outlining how PSM should operate); and (4) specific requirements concerning PSM news and non-news content. In the latter dimension, objectivity emerged as one of the most critical expectations and a major source of dissatisfaction. While participants collectively value objectivity, they disagree on its definition. A deeper examination revealed that certain public expectations may be unattainable due to the simplistic view of objectivity held by some.

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Seaweed farming has been growing in prominence in the coastal region of Kwale County, Kenya, as a livelihood led by women since the turn of the century, however the sector remains far below its full productive capacity. As such, this study explores the factors that influence women’s ability to access seaweed farming through engagements with the theories of intersectionality. The Blue Empowerment Project is seeking to upscale seaweed farming in this region to promote women’s empowerment and this study questions the extent to which men should be included in such an endeavour. It finds that several factors may intersect with gender to create varying levels of (dis)advantage amongst women in this region, and that we may need to reframe the conceptualisation of women’s empowerment to be inclusive of men. This study therefore makes a range of recommendations for the BEP, development practitioners in general, and researchers to inform them of how women’s empowerment initiatives may be made more inclusive and transformational.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

The effects of climate change health impacts on urban health care systems and vulnerable populations are a researched topic with foundations on urban risk management, urban health methodologies, and sustainable urbanization. As climate change is a dynamic and transformative global issue the gap between adaptation and mitigation efforts and urban planning relies, among other things, in the limitations of previous studies of risk management structures tailored to the existing strategy to calculate the uncertainties and predict their influence on urban systems and subsystems. Moreover, as climate and health is a well-researched issue, it is also complex as the methodologies and strategic approach to minimize health risks of climate change is intrinsically contingent to risk methodologies and policy-making processes that are efficient with support of knowledge-based information. This paper emphasis the need for focusing on urban health risk management methods that serves to identify potential opportunities, and then manage and take action to prevent adverse health effects. It also emphasizes the probability of events and their consequences, which are measurable both qualitatively and quantitatively.

Childhood nutrition is a cornerstone of long-term health, yet many children exhibit reluctance to consume healthy foods such as vegetables. This aversion can be influenced by various factors, including food neophobia and the sensory and visual appeal of the foods presented. Understanding how visual cues affect children's willingness behaviors can provide insights into effective strategies to enhance their dietary habits. This study aims to investigate the liking and emotional responses on the relationships between intrinsic and extrinsic cues and children's willingness to eat and to ask parents to buy. To understand how these factors influence children with food neophobia food-related behaviors and to identify effective strategies to promote healthier eating habits. A sample size consisting of 420 children recruited was needed in this cross-sectional study. A validated and reliable self-administered questionnaire was employed. Independent t-test and ANOVA were used to test the differences between gender and food neophobia means. Spearman correlations were used for correlation analysis. Hierarchical regression analyses were conducted to explore the relationships among intrinsic cues, extrinsic cues, and the mediating effect of liking and emotional responses. Attributes such as plate color and shape significantly influence children's food-related behaviors and their emotions. Liking and emotional responses significantly mediates the relationship between intrinsic/extrinsic cues and willingness. Positive visual cues experiences are crucial for increasing children's inclination to purchase and consume. Positive emotional responses enhance acceptance and purchase. There are significant differences between boys and girls. Boys prefer blue and triangular plates, while girls prefer pink plates and generate more positive emotions. Children with food neophobia will initially experience a disorder, but its negative effects can be mitigated by increasing sensory appeal and emotional engagement. By employing strategies designed to enhance visual cues and liking and emotions, children’s willingness to choose healthy eating habits can be effectively increased.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Innovation and sustainability are key elements gaining important positions in public and private organizations’ agenda in recent years. Whilst innovation drives for more productivity, efficiency and competitiveness, sustainability incorporation into the development of the organizations outlines as a counterbalance. It helps directing the innovative endeavors of the organizations towards more responsible activities in terms of environmental, economic and social impacts. To help achieve that, standardization offers valuable tools to orient organizational development efforts towards sustainability. This research aims at exploring the plausible connection between use or implementation of standards and pursuit of sustainability in an important industrial sector in Romania – food industry. The objective of the research is to determine which of the two iden-tified hypothesis can be scientifically supported using the quantitative research methods. The expected results are that more than simply following short-term objectives, companies that con-sciously use recognized standards in their activity pursue long-term sustainability.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

When dealing with limited sample sizes or missing values in time series data, achieving high accuracy in forecasting becomes challenging. This challenge is particularly common in wind energy forecasting, where many wind farms lack complete data. In this paper, we employ the widely-used ARIMA (Autoregressive Integrated Moving Average) model for time series forecasting. To address the difficulties posed by limited sample sizes and missing values, we adopt a unique approach by utilizing multiple ARIMA models for different datasets. A key distinction from other multiple models methods for time series forecasting lies in each model within our approach using its own dataset, making the fusion process more intricate. To overcome this, we incorporate neural networks and two techniques for model fusion: direct fusion with a learning mechanism and compensation for missing data through training. For each ARIMA model, we introduce a noise estimation method to circumvent the white noise assumptions inherent in ARIMA models. Finally, we apply these methods to wind energy prediction, and our experimental results showcase a significant enhancement in forecasting accuracy.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

We introduce a new generalized inverse which is a natural generalization of (pseudo) right core inverse in a Banach *-algebra. We characterize this generalized inverse by using right core and quasi-nilpotent decomposition. We then present its polar-like characterization and investigate related algebraic properties. Finally, the right core-EP inverse is characterized by certain new ways.

New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N'-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or by a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalon- dianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichlorophenyl)- 7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was con-firmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computa-tional scheme. The results revealed that the rate limiting step is a cyclization process leading to the closure of 1,4-dihydropyridine ring with an activation barrier of 28.8 kcal/mol. Some of dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D . Additional-ly, ADMET parameters were calculated and molecular docking studies were performed to identify potential protein targets.

Reviewed are recent efforts leading to chemo-enzymatic syntheses of strongly fluorescent ribosides of nucleobase analogs, potentially applicable in analytical biochemistry and cell biology. Described are syntheses and properties of fluorescent purine, 8-azapurine and etheno-purine ribosides, obtained using various types of the purine nucleoside phosphorylase (PNP) as catalysts of ribosylation, and -ribose-1-phosphate (r1P) as a second substrate. In several instances, the ribosylation sites were different than the canonical purine N9. Some of the obtained ribosides show fluorescence yields close to 100%. Their main applications are assays of PNP, nucleoside hydrolases, and other enzyme activities both in vitro and, possibly, within the living cells, using fluorescence microscopy.

Climate change has become a major agenda item in international relations and in national energy policy-making circles around the world. This article studies the surprising evolution of the energy policy, and more particularly the energy transition, currently happening in the Arabian Gulf region, which features some of the world’s largest exporters of oil and gas. Qatar, Saudi Arabia and other neighboring energy exporters, plan to export blue and green hydrogen across Asia as well as towards Europe in the years and decades to come. Although poorly known and understood abroad, this recent strategy doesn’t threaten the current exports of oil and gas (still needed for a few decades) but prepares the evolution of their national energy industries towards the future decarbonized energy demand of their main customers in East and South Asia, and beyond. The world’s largest exporters of Liquefied Natural Gas, Qatar, has established industrial policies and projects to upscale CCUS, which can enable blue hydrogen production, as well as natural carbon sinks domestically via afforestation projects.

In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x104 – 2x107 CFU per ml and has a sensitivity of S = 1.655x105 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10-9 grams (g) which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree's utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to her full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA) utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

As modern systems are becoming more complex their control strategy cannot longer relay only on measurement information that usually comes from probes but also from mathematical models. Those systems models can lead to unbearable computation times due to their own complexity, turning the control process non-viable, which leads to the implementation of surrogate models that enable to achieve estimates within acceptable time to take decisions. A control trained with Deep Reinforcement Learning algorithm, using a Physics-Informed Neural Network to obtain the temperature map on the following time step, replaces the need of running Direct Numerical Simulations. On this work we considered an 1D heat conduction problem, which temperature distribution feeds a control system to activate a heat source aiming to obtain a constant, previously defined, temperature value. With this approach, control training becomes much faster without the need of performing numerical simulations or laboratory measurements, as well the control is taken based on Neural Network enabling its implementation on simple processors to edge computing.

In the current era of emerging technologies and cutting-edge inventions, it is equally important to consider the ethical aspects of research and innovations to have an ethical space for the sustainable progress and safety of humanity. The field of nanotechnology research and innovation often faces criticism due to its potential adverse impacts on health, the environment, limited accessibility, high costs, and concerns about data privacy. Therefore, it is crucial to address and resolve these ethical issues systematically. In this regard, we present our findings and methods for exploring the application of the ethics technology assessment method by considering its relevance at different stages of innovation development. Specifically, the present work provides a conceptual framework for ethics technology assessment focused on evaluating a significant innovation in nanotechnology within the domain of food safety with specific reference to mycotoxin remediation. By leveraging the value-sensitive design approach, we described various strategies for analyzing the ethical implications of nanotechnology-based innovations in mycotoxin remediation. Through comprehensive ethics technology assessment, nanotechnology-based innovations can be guided toward becoming more value-oriented, thereby making substantial contributions to social progress.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, TMPRSS2, and AP2-associated protein kinase 1. In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of drug candidates to target receptors, providing insight into their potential efficacy. However, it is crucial to consider both the advantages and limitations of these studies and to complement them with experimental validation to ensure the efficacy and safety of identified drug candidates.

Water footprint has been widely used to illustrate the consumption of water in many situations; for instance, in products, processes or regions of interest. In this work, we analyzed – using a sensitivity analysis approach – the effect of some variables in the calculation of the water footprint in the viticulture in Brazilian Serra Gaúcha (the major producing region of Brazilian Wine).The classical Penman-Monteith model for evapotransporation was considered, with uncertainties in some parameters (dead mulch covering fraction in the vineyard, maximum temperatures for some months, altitudes and latitudes of the site). The sensitivity analysis was conducted using the SAFE toolbox under Octave framework. The results indicated that the the portion of the water footprint corresponding to the evapotranspiration is more sensitive to the values of mulch covering fraction and the altitude of the site in comparison with the latitude and the maximum temperatures.

Human serum albumin (HSA) corona formation at polymer microparticles of a spheroidal shape was studied using dynamic light scattering and laser Doppler velocimetry (LDV). Physicochemical characteristics of the albumin comprising, the zeta potential and the isoelectric point were determined as a function of pH for various ionic strengths. Analogous characteristics of the polymer particles were carried out. The adsorption of albumin on the particles was monitored by electrophoretic mobility measurements (LDV). The stability of the HSA functionalized particle suspensions under various pHs and their electrokinetic properties were determined. The deposition kinetics of the particles on mica, silica and gold sensors were determined in situ by optical microscopy, AFM and by the quartz microbalance (QCM) under diffusion and flow conditions. The obtained results were interpreted in terms of the coarse-grained random sequential adsorption model that allowed to estimate the range of applicability of QCM for determining deposition kinetics of virus and bacteria at abiotic surfaces.

Several studies with kaempferol (KP) and linearolactone (LL) have shown antiparasitic activities. However, the toxicity of treat-ments with both active principles is unknown. Therefore, this study aimed to evaluate the toxicological effects of treatments with KP and LL on the amoebic liver abscess (ALA) model in M. auratus administered intraperitoneally (i.p.). For this, ALA in-duction was carried out in male hamsters with 1.5 x105 E. histolytica trophozoites inoculated in the left hepatic lobe. The lesion evolved for four days and the i.p. of the treatments with KP (5 mg/kg body weight/day) and LL (10 mg/kg body weight/day) was carried out for four consecutive days. For histopathological evaluation, NMR studies, paraclinical analysis, and necropsy were performed. The results revealed that the inhibition of ALA by KP and LL were similar to that metronidazole (MTZ). Biochemical parameters revealed hepatic and renal alterations in all treatment groups, mainly for KP (AST and BUN). The lesions found in the organs were those that are directly linked to the pathology. In conclusion, KP and LL decrease ALA development but have few toxicological effects. Both compounds combined with MTZ could be therapeutic alternatives for amoebiasis caused by E. histolytica.

Background: The purpose of this review is to clarify the natural course of Benign Paroxysmal Torticollis (BPT) and to update the relationship of this disorder with migraine. BPT belongs to a group of “episodic syndromes that may be associated with migraine” and is diagnosed when according to diagnostic criteria of the International Classification of Headache Disorders, 3rd edition. It is present in infants and young children and it is an underdiagnosed manifestation, because it is not well recognized and in most cases with a benign evolution, but requires careful differential diagnosis. It was first described by Snyder in 1969 as a movement disorder, a cervical dystonia consequent to labyrinthic disorder.Materials and methods: The PubMed and Web of Science databases were consulted from 1968 to 2024, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines ,2020.( PRISMA)Results: 113 articles were identified, 86 selected and 20 considered for the purpose of this review. The clinical studies were considered in relation to evolution, cognitive and motor development, to genetic and not genetic etiology, to the relationship with migraine with and without aura, vestibular migraine, hemiplegic migraine, and paroxysmal vertigo.

Promoting the sustainable development of resource-based cities is of great significance to the ecological protection and high-quality development of the Yellow River Basin. Combining the environmental status and economic development, we objectively evaluate the ecological safety level of resource-based cities in the Yellow River Basin, compare and analysis the main factors affecting the ecological safety of different resource-based cities, and formulate precise and differentiated ecological safety protection measures in river basins to achieve high-quality development. Taking the Yellow River Basin as an example, this paper analyses the ecological level of the Yellow River Basin based on the theory of sustainable development, calculates the ecological safety level of 30 resource-based cities in the Yellow River Basin from 2006 to 2020 by TOPSIS model, and makes convergence analysis by classification. Through the DID empirical test of sustainable development planning policy on ecological safety factors, distinguish the development characteristics of different resource-based cities. The results show that: (1) the ecological safety level of resource-based cities in the Yellow River Basin is generally developing well, and there are differences among different types of resource-based cities; (2) the kinetic energy of sustainable development of resource-based cities in the Yellow River Basin is mainly industrial transformation, and the power of science and technology is insufficient; (3) local governments pay limited attention to environmental protection, and the sustainable development planning of resource-based cities in 2013 mainly promotes the adjustment of industrial structure of resource-based cities.

Astragaloside IV (AIV) – triterpenoid saponin from the Astragalus mongholicus roots with the proved acetylcholinesterase (AChE)-inhibitory capability was used as the substance with the potential to attenuate memory impairment. Scopolamine (SCOP), antagonist of muscarinic cholinergic receptors and lipopolysaccharide (LPS), neuroinflammation inducer were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in the SCOP-treated mice was attenuated by the earlier intraperitoneal (ip) administration of AIV in the dose of 25 mg/kg. The reduction of memory impairment by LPS was not observed, therefore AIV does not reverse memory impairments through the anti-inflammatory mechanisms. All the studied doses of AIV did not affect basic locomotor activity of mice. As a result of the post-mortem analysis of mice body tissues, the largest content of AIV was determined in the kidneys, then in the spleen, liver and the smallest one in brain by mass spectrometry.

In this study, five polyphenol compounds (reference substances, ref.) were added to Stokesia laevis (Slae26) ethanolic extract (5 mg GAE / mL) in order to test their antiproliferative effects on human colon tumor cell line Caco-2 (ATCC-HTB-37). The five phenolics (ref.) are luteolin-7-O-glucoside (orientin), luteolin-8-C-glucoside (cinnaroside), caffeic acid, gentisic acid and para-aminobenzoic acid (PABA), and they were combined in ratio 1:1 between the active compounds in samples (GAE : ref.). Results indicated certain antiproliferative effects of Slae26 (IC50=36 μg GAE/mL sample), of the five reference compounds, but mainly of Slae26 combinations with the five phenolics tested (ref.). Punctually, there were obtained IC50 values around 5 μg/mL sample, signifying real therapeutic usefulness and antitumor potency of Slae26 combinations with the five food bioactive compounds tested. In silico docking studies provided potential therapeutic agents to inhibit the catalytic domain of human tankyrase 1 (TNKS1) in the series of food bioactive compounds tested, and revealed luteolin-7-O-glucoside high effectiveness.

Based on the need for real-time sag monitoring of Overhead Power Lines (OPL) for electricity transmission, this article presents the implementation of a hardware and software system for online monitoring of OPL cables and cable sag determination. The mathematical model based on differential equations and the methods of algorithmic calculation of OPL cable sag are presented. Considering that, based on the mathematical model presented, the calculation of OPL cable sag can be done in different ways depending on the sensors used, and the presented application uses a variety of sensors. Therefore, a direct calculation is made using one of the different methods. Subsequently, the verification relations are highlighted directly and, respectively, the calculation by the alternative method, which uses another group of sensors, to generate both a verification of the calculation and the functionality of the sensors, thus obtaining a defect observer of the sensors. The hardware architecture of the OPL cable online monitoring application is presented, together with the main characteristics of the sensors and communication equipment used. The configurations required to transmit data using the ModBUS and ZigBee protocols are also presented. The main software modules of the OPL cable condition monitoring application are described, which ensure the monitoring of the main parameters of the power line and the visualisation of the results both on the electricity provider's intranet using a web server and MySQL database, and on the Internet using an Internet of Things (IoT) server. This categorisation of the data visualisation mode is done in such a way as to ensure a high level of cyber security. Starting from the mathematical model of the OPL cable sag calculation, it goes through the stages of creating such a monitoring system, from the numerical simulations carried out using Matlab to the real-time implementation of this monitoring application. The main modules of the application software are: the software module for reading quantities from the sensor network through a ModBUS Input/Output (I/O) server, the software module for real-time calculation of the OPL cable sag, the software module for read/write operations based on MySQL type data, the software module for transferring data to the user's intranet through a web server, and the software module for viewing data by authorised users based on user and password through an IoT server. The development software environments used are Matlab and Laboratory Virtual Instrument Engineering Workbench (LabVIEW).

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Objective: The Covid-19 pandemic has raised significant concerns about public health, particularly in terms of mental well-being due to heightened fear and uncertainty. The findings of this study are based on a survey conducted to evaluate the mental health status of the general population in Croatia during the Covid-19 pandemic. Methods: A survey conducted randomly and cross-sectionally included 588 respondents from all 21 counties in Croatia. The survey gathered demographic data and assessed various factors related to pandemic response measures and mental health using the Mental Health Continuum-Short Form (MHC-SF) scale. Results: Despite feeling adequately informed about Covid-19 (76.0%), most respondents (60.8%) expressed concerns about their loved ones during the pandemic. There were significant numbers who felt there was no risk of infection (50.9%) or believed they would not get infected (40.2%), while 72.4% were content with government measures. Statistical analysis indicated that mental health was not significantly different between genders, but age-related differences were evident, with those under 21 experiencing the most distress. The lowest level of psychological and social well-being was observed in respondents who were unemployed. Conclusions: The study identifies vulnerable groups in the Croatian population during the pandemic, including younger individuals, those on parental leave, students, and the unemployed, who exhibited worse mental health. The importance of implementing targeted mental health interventions to support these vulnerable groups is highlighted by these findings.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Based on a constant volume combustion chamber, the initial ambient pressure effect on combustion performance and flame propagation of the active and passive pre-chamber ignition systems were studied. Compared with the passive pre-chamber, the active pre-chamber can significantly expand the lean combustion limit, enhance the ignition and combustion performance, and speed up the combustion of the main combustion chamber. At slightly lean combustion conditions, the heat release performance has a positive correlation with the initial ambient pressure. As the premixed λ increases, the heat release performance and the initial ambient pressure begin to become negatively correlated. Ignition delay can be minimized by controlling the excess air coefficient in the pre-chamber close to the stoichiometric ratio. The high ambient pressure in the constant volume chamber greatly reduces the mixture entrainment ability of the jet flame at lean combustion conditions, thereby reducing the combustion speed and peak heat release rate.

Current trends in systemic risk literature provide new insights into multi-hazard risks that interact and compound with built environments, creating more significant impacts on socio-economic and human systems. Recurrent natural hazards and extreme weather events are more likely to compound and cascade into more impactful events, especially in vulnerable societies. In small-island communities (SICS), including large archipelagos and Small Island Developing States (SIDS), the long-term impact of multi-, compounding-, and cascading-hazards (MCC hazards) can result in persistent vulnerability and residual risks. This is due to delayed responses, limited resources, poverty, fewer evacuation options, and inadequate markets and infrastructure. Using Ternate, a densely populated small volcanic island in North Maluku, Indonesia, as a case study, this paper assesses the impacts of seven types of natural hazards: flash floods, landslides, extreme weather, extreme waves and abrasion, earthquakes, tsunamis, and volcanic eruptions. The research focuses on the multi-hazard impact on population, land use, and infrastructure exposures in 60 villages in Ternate. The findings highlight population density, land use, and infrastructure exposure to multi-hazard risks, providing valuable information on potential losses in future hazard events.

The aim of this manuscript is to synthesize and characterize novel silylated Sm3+ and Eu3+ complexes and incorporate them into mesoporous silica nanoparticles (MSNs) and dense silica nanoparticles (DSNs). Sm3+ and Eu3+ ion complexes were chosen for their strong UV-visible emission, deep-red luminescence, and effective interaction with bidentate organic ligands, such as 2-thenoyltrifluoroacetone (tta) and 1,10-phenanthroline (phen). Silylated ligands were employed as coupling agents to form covalent bonds between the complexes and an oxide matrix via a conventional sol-gel process. This approach aims to enhance the thermal stability and photophysical properties of the resulting hybrid material compared to free complexes. The new silylated-bidentate ligand complexes, using tta and phen as organic ligands and 3-chloropropyltriethoxysilane as the silylating agent, were characterized by FTIR, luminescence spectroscopy, and luminescence decay. After incorporation into silica nanoparticles, the hybrid materials were characterized by SEM, TEM, DLS, zeta potential, SAXS, porosity, surface area measurements, luminescence spectroscopy, and MTT assay. The results confirm the successful synthesis of new luminescent silylated complexes with high luminescence intensity and their incorporation into silica nanoparticles.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

Despite the recognized influence of body mass on combat techniques, the relationship between body segment mass (BSM) and combat moves remains unexplored. This study aimed to examine the relationship between striking arm mass (SAM), kicking leg mass (KLM), and body mass (BM) with the dynamic forces of the direct punches (DP), palm strikes (PS), elbow strikes (ES), front kicks (FK), and countermovement jumps (CMJ) performance. Sixteen male military cadets (22.3 ± 1.8 years, 181.4 ± 7.0 cm, 82.1 ± 8.5 kg) performed combat techniques, with performance measured by using a force plate and body segment mass assessed by Dual-energy X-ray absorptiometry. Spearman's correlation analysis, the Wilcoxon test, and Cohen's d were applied. Results indicated the relationship between KLM or BM and FK impulse (r = 0.64, p = 0.01; r = 0.52, p = 0.04, respectively) and CMJ impact force (r = 0.80, p ≤ 0.01; r = 0.70, p ≤ 0.01, respectively). Moreover, FK peak and impact forces were moderately correlated with CMJ jump height (r = 0.74, p ≤ 0.01; r = 0.77, p ≤ 0.01). The highest relationship was found between KLM and FK impulse; however, the difference in variability explained by KLM versus body mass is only 12%. This suggests that knowledge of BSM did not provide a significantly better estimate of the dynamic forces of the punches and FK than BM.

In recent years, the prevalence of tobacco and electronic cigarette (e-cigarette) use among adolescents has raised significant public health concerns worldwide. This study aims to investigate respiratory symptoms among Polish adolescents. We conducted an online survey among Polish school students from all provinces, collecting data over two months in Spring 2021. Students voluntarily complete the anonymous survey, answering questions about respiratory symptoms, smoking habits (both traditional and electronic cigarettes), and demographic information. Analysis focused on four subgroups: non-tobacco users, traditional cigarette smokers, e-cigarette users, and dual users, totaling 10,388 pupils aged 12-18 years, predominantly attending secondary technical and comprehensive schools. A total of 10388 pupils participated in the study, 55.6 % (5778) of whom were girls and 44.4 % (4610) boys. Adolescents, who admitted using both e-cigarettes and traditional cigarettes experienced more frequent episodes of cough during the day (39.70%) and at night (18.40%) compared to their peers in other groups. Chest discomfort, including pain and pressure, was also reported more often by adolescents, who used e-cigarettes and traditional cigarettes concurrently (27.60%) compared to their peers in other groups. Chest pressure was experienced less commonly by non-smoking adolescents (14.40%) than by smokers (18.90%). Higher severity of cough during the day and at night was observed in the group of adolescents using traditional cigarettes and e-cigarettes concurrently compared to the other groups. The adolescents in the dual user group experienced more severe dyspnoea and wheezing compared to the other groups included in the comparison. The results of this study confirm the correlation between the occurrence of respiratory symptoms in adolescents who smoke cigarettes, use e-cigarettes and in dual users. The respiratory symptoms occur most frequently and are the most severe in the group of adolescents who use e-cigarettes and traditional cigarettes

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

Members of the genus Armillaria are widespread forest pathogens against which effective protection has not yet been developed. Due to their longevity and the creation of large-scale cloning of Armillaria individuals, the use of mycoviruses as biocontrol agents (BCAs) against these pathogens could be an effective alternative. This work describes the screening of double-stranded RNA banding patterns as a first approach for potential virus discovery and the use of stranded total RNA-seq for viral detection and characterization in Armillaria spp. collected in the Czech Republic. A total of five single-stranded RNA viruses were detected in Armillaria ostoyae and A. cepistipes, including the first virus of the family Tymoviridae found infecting a member the genus Armillaria and four viruses belonging to the recently described virus group "ambiviruses" with circular ambisense genome organization. Both hammerhead (HHRz) and hairpin (HpRz) ribozymes were detected in all the ambiviricot sequences. Armillaria viruses were compared by phylogenetic analysis and confirmed their specific host by direct RT-PCR, which showed the occurrence of interspecies transmission.

Many studies utilize sensors to measure foot plantar pressure and analyze gait patterns, often focusing on assessing weight-bearing symmetry or asymmetry compared to control groups. However, a critical question arises: does the selection of the control group significantly impact study outcomes? Does chronic low back pain affect foot plantar pressure measurements? This experimental study involved 23 participants, including healthy individuals and those without foot disorders but with chronic low back pain. Dynamic foot pressure measurements were conducted using the Ortopiezometr, and data were analyzed using the "Steps" program. Participants were divided into two groups: Group 1 comprised completely healthy individuals, while Group 2 consisted of individuals without foot problems but with moderate chronic low back pain. The findings highlight a prevalence of energy release in the forefoot sensors compared to the hindfoot for both the right and left legs in most cases. Even among healthy volunteers, achieving perfect symmetry in the maximum values on the sensors for the right and left feet was a challenge. Results showed no statistically significant differences in energy released on specific sensors or duration of gait phases between the groups. Essentially, this suggests that foot pressure patterns are comparable between healthy individuals and those with low back pain. The use of sensor-equipped inserts for pedobarographic examinations indicates that, in cases of degenerative changes in the lumbar and sacral spine without accompanying acute pain, gait patterns resemble those of the healthy population.

The analysis of the key factors which prevent or contribute to the promotion and development of the Power Purchase Agreements (PPAs) in order to meet the sustainability goals represents an important issue which worth being investigated, especially in the situation in which entering in bilateral relations inside this contract has a powerful meaning in achieving new climate targets, developing and improving the use of green energy, and promoting a sustainable green economy. The main goal of this research is to identify and analyze the main factors which help or pre-vent the promotion and development of a PPA, in order to meet the sustainability goals by promoting a green economy. For this research survey based on comparative analysis, questionnaires and interviews with energy experts, Spearman’s correlation matrix and IBM SPSS Statistics for Window are also used. The results suggest that although there are positive interest and an open attitude towards the PPA from both sides (sellers and buyers), but there is still place for improvement, the lack of knowledge or the insufficient measures taken so far being two of the reasons way until now in Romania we do not have a developed PPA market and the level of knowledge regarding this type of mechanism is quite low.

Carbonate reservoirs, influenced by depositional and diagenetic processes and characterized by features like faults and vugs that impact storage capacity, require more than traditional Borehole Imaging logs (BHI) for accurate porosity data. This data is essential for geological assessments, production forecasting, and reservoir simulations. This work aims to address this limitation by developing methods to measure and monitor the sustainability of carbonate reservoirs and exploring the application of sustainability principles to their management. The study integrates BHI and conventional logs from two wells to classify porosity-based facies within the Barra Velha Formation (BVF) in the Santos Basin. The methodology involves four steps: (i) analyzing conventional logs; (ii) segmenting BHI logs; (iii) integrating conventional and segmented BHI logs using Self-Organizing Maps (SOM); and (iv) interpreting the resulting classes. Matrix porosity values and non-matrix pore sizes categorize the porosity into four facies (A to D). Facies A has high non-matrix porosity with 14,560 small megapores, 5,419 large megapores, and 271 gigapores (71.9%, 26.76%, and 1.34% of the 20,250 pores, respectively). Facies B shows moderate non-matrix porosity with 8,669 small megapores, 2,642 large megapores, and 33 gigapores (76.42%, 23.29%, and 0.29% of the 11,344 pores, respectively) and medium matrix porosity. Facies C exhibits low non-matrix porosity with 7,749 small megapores, 2,132 large megapores, and 20 gigapores (78.27%, 21.53%, and 0.20% of the 9,901 pores, respectively) and medium matrix porosity. Facies D has low non-matrix porosity with 9,355 small megapores, 2,346 large megapores, and 19 gigapores (79.82%, 20.02%, and 0.16% of the 11,720 pores, respectively) and low matrix porosity. The novelty of this work lies in integrating data from two sources to classify porosity across the Pre-Salt reservoir interval, serving as a proxy for preliminary litho-facies identification without core data. This study advances our understanding of carbonate reservoir sustainability and heterogeneity, offering valuable insights for robust, sustainable reservoir characterization and management in the context of global environmental and geological changes.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

This study proposed to use wearable EEG to study the impact of vipassana mindfulness practice on beginner's physiological and neurological responses. Mindfulness meditation has been shown to have numerous benefits, including stress reduction, improved attention and cognitive function, and enhanced emotional regulation. The roots of mindfulness meditation in Buddhism emphasize cultivating present-moment awareness and insight. However, the neural mechanisms together with physiological mechanism and their interaction underlying these benefits remain poorly understood. Method: One middle age man (50 years old) participated in this longitudinal study using wearable EEG to investigate the neurophysiological change during a one-month consecutive vipassana mindfulness practice. Both EEG and heart rate responses were recorded each time, before (5 minutes), during (20 minutes), and after (5 minutes) meditation sessions. The EEG and HR data were analyzed by Matlab and EEGlab to examine changes in brainwave activity and heart rate. Results: alpha peak frequency (APF) is significantly lower after mindfulness meditation, as shown by comparison of APF before mindfulness (pre-5) and during mindfulness practice (med-20), and comparison between APF of pre-5 and after mindfulness practice (post-5). The same is with the beta peak power. While for theta peak frequency, it is significant lower during mindfulness meditation (med-20), when comparing to either pre-5 or post-5. See figure 1a. However, peak power index is not so sensitive, and it is more obvious in theta wave band. That is, the theta power peak is significantly lower after meditation, as can be observed in comparison between pre-5 and med-20, also between pre-5 and med-20. See figure 1b. STATE Heart-mean (bpm) Heart-std(bmp) pre-5 69.88 3.88 med-20 68.36 2.81 post-5 69.55 4.13 t-value test (pre-med) 0.0694 0.0003 t-value test (pre-post) 0.7934 0.3656 t-value test (post-med) 0.3193 0.0001 Table 1. The difference of Heart rate (mean and SD) in before (pre-5), during (med-20) and after (post-5)mindfulness meditation. We find significant change in standard deviation (SD) of heart rate between meditation and non-meditation mental states, as shown in table 1. The study provides insights into the underlying neurophysiological mechanisms of mindfulness meditation using wearable EEG devices. It demonstrates that in term of EEG measurement, spectrum frequency can be more sensitive than spectrum power; also heart rate variability as measured by SD is more sensitive to mean of HR. The proposed study contributes to the literature by using wearable EEG devices to collect data in a more accessible and convenient manner.

Consumption of ultra-processed foods is associated with abdominal obesity, but this association has not yet been investigated in individuals on hemodialysis. This cross-sectional study, developed with 1014 individuals, aimed to analyze the prevalence of abdominal obesity and its association with the consumption of ultra-processed foods in individuals on hemodialysis. Consumption of ultra-processed foods was measured using a questionnaire, whose list of foods was based on the Surveillance System of Risk and Protective Factors for Chronic Non-Communicable Diseases through Telephone Enquiry. Waist circumference was used to determine the presence of abdominal obesity. The difference in proportions between the independent variables and the outcome was verified using Pearson's chi-square test. Hierarchical logistic regression was used to determine the association between the outcome and the independent variables. The prevalence of abdominal obesity was 77.22%. In the final model, higher consumption of ultra-processed foods, be male and an adult, have between 8 and 11 years of schooling and practice physical activity below the recommended level increased the chances of having abdominal obesity. The research provides a basis for the creation and improvement of public policies that promote improvements in these health determinants.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

Background/Objectives: PEMF therapy has gained significant attention due to its potential benefits in promoting tissue repair and improving overall well-being. Recent publications in the field of exercise physiology, showed that pulsed electromagnetic fields (PEMFs) enhanced the velocity and the quantity of muscle O2 available and the rate of muscle oxygen extraction and utilization, in semi-professional cyclists, during a heavy constant-load exercise. In this paper, we investigate the effect of stimulation on muscular activation, in sedentary young people, during a constant-load exercise, performed at moderate intensity. Methods: Nine male sedentary young people, partic-ipated in this study. The response of the muscle activity, was recorded by surface EMG and assessed measuring the root mean square (RMS) normalized to the peak of the maximum voluntary con-traction. Data were collected in the right vastus Medialis (RVM) and right Biceps Femoris (RBF) at the baseline (standstill sitting), on warm-up (unloaded cycling) and during 30 minutes of con-stant-load exercise, in two experimental conditions (PEMF ON vs PEMF OFF). Results: The mul-tivariate analysis of variance performed on RVM showed a significant effect of PEMF in both warmup and exercise, while on RBF showed a significant effect of PEMF and warmup. Conclusions: PEMF strongly enhanced the amplitude of muscle activity in young sedentary people. The increase in the amplitude of the muscular response may lead to a higher oxygen consumption and release.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Diarrhea is a common occurrence following vascular organ transplantation, including kidney transplants. It can be induced by non-infectious factors, adverse effects of immunosuppressive drugs, or infectious agents such as viruses, bacteria, fungi, or parasites. Intestinal protozoan parasites, include Cryptosporidium spp., are causes of infectious diarrhea particularly in immunocompromised patients. This review aims to summarize reports on epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in adult patients, particularly following kidney transplantation.

Polymer inclusion membranes (PIMs), which contained cellulose tri-acetate used as a polymer base, a plasticizer in the form of o-NPOE, and meso-tetra methyl tetrakis-[methyl-2-(4-acetlphenoxy)] calix[4]pyrrole (KP) used as a carrier, were prepared and tested for the effective purification of aqueous solutions of methylene blue dye. The scanning electron microscope (SEM), thermogravimetric analysis (TGA), and attenuated total reflection Fourier transform infrared (ATR-FTIR) were used to define the microstructure and surface of PIMs. Experimental results showed that with the increased concentration of methylene blue in an aqueous solution, the removal percentage also increased. Further observation also showed that the flux increased with the rise of the source phase pH values from 3 to 10. The carrier and plasticizer content in the membrane significantly influenced the membrane’s transport properties. The optimal composition of the membrane in per cent by weight was for KP: 74% plasticizer; 18% support; 8% carrier. It was shown that the membrane with optimal composition showed good reusability and enabled the easy and spontaneous separation of methylene blue from aqueous solutions.