Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Aims: To study the effects of pyridoxal phosphate (PLP) on oxidative stress in isolated pancreatic acinar cells. We have previously shown that PLP has cytoprotective and insulinotropic effects on mice islet cells in vivo and in vitro studies. Main methods: Acinar cells were isolated from three months old WNIN male rats and were cultured in vitro for a period of 24 h in CO₂ incubator. Later the cells were divided into four groups as untreated (group 1), H₂O₂ treatment (group 2)_, PLP treatment (group 3) and PLP followed by H₂O₂ treatment (group 4). Cell viability was confirmed using MTT assays, oxidative stress levels were measured with ROS assay, change in different protein levels were recorded by flow cytometry. The acinar cells insulin secretion assay was performed with ELISA. The amylase protein expression was assessed using confocal microscopy. Key findings: The cell viability of acinar cell in group 1 was considered as 100%, while in group 2 it was reduced to 82% due to H₂O₂ effect, and in group 3 (99.8%) and group 4 (99.5%) were near to group 1 due to the cytoprotective effect of PLP. The ROS levels were increased by 1.47 folds in group 2, while PLP decreased to 1.02 fold in group 4, which was comparable with the changes in group 1. Beneficial effects of PLP were also observed from the increased expression levels of acinar cells are amylase -2.01, neurogenin-3-9.51, PDX-1- 23.6 and insulin-13.5 in group 3 compared to group 1. The specificity of PLP’s response was confirmed by amino oxy acetic acid (AOAA), a specific PLP inhibitor. The increased amylase protein localization with PLP was confirmed by confocal microscopy. Insulin secretion efficiency of acinar cells was observed to be 6.13 folds higher at basal and 24.63 fold higher at stimulated levels in group3 compared to group1. Significance: Our results advocate the antioxidant and cytoprotective effects of PLP on the pancreatic acinar cell along with increased pancreatic marker expressions of amylase,PDX-1, neurogenin-3 and insulin proteins.

Knowledge is not merely the characteristic of certain pieces of information being deemed true and justifiable, but rather a process. Within an axiomatic system, the set of information that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the process of justification (exchange of information), if it consistently justifies a particular piece of information, it elevates it to knowledge. In this paper, we provide a framework for knowledge within an axiomatic model where we define the fundamental elements of communication and grammar. As a result, the structure dictates that knowledge, to be considered as such, must be investigateable by anyone who utilizes it in its entirety, both in form and content. Ultimately, the development of knowledge processing, referred to as \emph{knowmatics}, represents a clear evolution of the computer science that processes information (subset of knowledge).

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Shigella and Salmonella have been implicated in neonatal sepsis, food poisoning, and bacteremia. Their increasing resistance to antibiotics has undermined treatment options, constituting a public health crisis. Also, the scarcity of new antibiotics in the development pipeline compounds multidrug-resistance (MDR). Hence, there is a need to potentiate antibiotics to mitigate resistance. This study leveraged riboflavin to re-sensitize fluoroquinolones and carbapenems against MDR Shigella and Salmonella spp. Disk diffusion, microbroth-dilution, chequerboard, and time-kill assays were used to determine resistance profiles and riboflavin-antibiotic activity. Biofilm-formation and bacterial viability (after riboflavin-antibiotic challenge) was determined with crystal-violet and Macrophage infection assays, respectively. Strains exhibited >80% resistance to fluoroquinolones and carbapenems, with 160–320 µg MIC ranges and 0.5–2 FIC, indicating no synergy. At 40–80 µg riboflavin, there was two-fold reduction in bacterial survival, with meropenem-riboflavin exhibiting significant reduction and FIC of 0.075 indicating high synergistic activity. Biofilm-formation was altered (from strong to weak phenotype) with 40 µg riboflavin-antibiotic treatment. There was a 40–70% reduction in bacterial survival in THP-1 cells treated with meropenem-riboflavin after 3 hours, and complete clearance between 24-48 hpi. Riboflavin potentiated fluoroquinolones and meropenem, leading to modulation of the host immune response for the clearance of the strains.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

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

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

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

As Li-ion batteries use is spreading, incidents in large energy storage systems (stationary storage containers, …) or in large-scale cell and battery storages (warehouse, recyclers, …), often leading to fire, are occurring on regular basis. Water remains one of the most efficient fire extinguishing agents for tackling those battery incidents and large quantities are usually necessary. Since bat-teries contains various potentially harmful components (metals and their oxides or salts, sol-vents…) and that thermal runway induced battery incidents are accompanied with complex and potentially multistage fume emissions (containing both gas and particles) the potential impact of fire run-off water on the environment should be considered and assessed carefully. The tests presented in this paper focus on the analysis of the composition of run-off waters used to spray NMC Li-ion modules under thermal runaway. It highlights that waters used for fire-fighting are susceptible to contain many metals, including Ni, Mn, Co, Li and Al mixed with other carbonaceous species (soot, tarballs) and sometimes undecomposed solvents used in the elec-trolyte. Extra-polation of pollutant concentrations compared with PNEC values showed that, for large scale incidents, run-off water could be potentially hazardous to the environment.

Long term Precipitation and temperature variations are one of the main determinants of climate variability of one’s area. The aim of this study is to determine trends variation in climatic elements of temperature and precipitation in the southern zone of Tigray regional state, Ethiopia. The station is assumed for the study of climatic records over southern zone of the region in detection for probable trends. The daily, monthly and annual precipitation totals and temperature observed at korem meteorological station were used for the period of 1981-2010 for Precipitation and 1985 – 2010 for minimum and maximum temperature. Summary of descriptive statistics and Mann Kendall test methods were employed for the observed data analysis to demonstrate any existence of possible trends. The main findings of the study indicated that the mean and maximum temperature had a general increasing trend; however, minimum temperature showed decreasing trend. In general annual temperature from 1985 – 2010 of the area showed a warming trend. Moreover analysis of the 30 years (1981-2010) annual precipitation showed a coefficient of variation ranging from 33.77 – 233 %. It indicated that the precipitation dissemination is not normal with large year to year variances.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Ammonium sulfate has been utilized in agriculture; however, there is a dearth of research on its application in maize cultivation subsequent to the implementation of nitrification inhibitors or coating. This study aims to analyze the impacts of various combinations of ammonium sulfate fertilizers on soil nutrients, plant nutrient uptake, yield, and fertilizer utilization efficiency in maize cultivation to ascertain the optimal and stabilized disposal method for ammonium sulfate. A completely randomized design was employed with five treatments (AU, the control using urea; AS, treatment using ammonium sulfate; ASN, treatment using ammonium sulfate with a nitrification inhibitor; ASG, treatment using oil-coated ammonium sulfate; ASD, treatment using oil-humic acid-coated ammonium sulfate). Results showed that: (1) Compared with AU and AS, ASN, ASG and ASD decreased the leaching rates of TN, NH4+-N and NO3-N to the 10-20 cm soil layer, and more residual N was obtained in 0-10 cm soil layer. The first-order kinetic equation Nt=N0(1-e-kt) can better fit the process of nitrogen accumulation and release, and the N release rate constant is AU>CK>AS>ASH>ASN>ASD; (2) Compared with AU and AS treatments, the plant dry weight, grain dry weight, spike width, spike length, and yields of maize increased by 8.85-11.08%, 12.98-14.15%, 2.95-3.52%, 5.50-5.65%, and 43.21-51.10% under ASG treatment respectively. The impact of effective spike number on maize yield was found to be significant, as demonstrated by the path analysis conducted in this study. Furthermore, the accumulation levels of nitrogen, phosphorus, and potassium within above-ground plants significantly increased under the ASG treatment compared to the AU and AS treatments. The partial productivity of nitrogen, phosphorus, and potassium increased by 1.43-1.51-fold under ASG treatment, while grain nitrogen balance, grain phosphorus balance, and grain potassium balance increased by 1.41-1.58-fold, 1.51-1.95-fold, and 1.15-l.96-fold respectively. The oil-coated ammonium sulfate, therefore, exhibited the optimal slow-release effect of nutrients, thereby achieving superior performance in enhancing maize production and efficiency.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

There is no doubt that seagrass beds constitute one of the most productive ecosystems in shallow coastal waters. Despite this, picoplankton in seagrass ecosystems has received relatively little attention. The purpose of this study was to compare picoplankton growth and mortality rates between seagrass and unvegetated habitats using chamber incubations. We tested two main hypotheses: (i) incubation with seagrass would result in higher bacterial growth rates due to increased DOM release from seagrass photosynthesis, and (ii) Synechococcus spp. would be lower in the presence of seagrass due to competition for inorganic nutrients. Our results showed bacterial growth rates of 2.31 and 2.44 d–1 without and with seagrass, respectively. In seagrass chambers, bacterial growth was higher than that in non-seagrass chambers, suggesting that organic carbon coming from the seagrass community may support bacterial production. Furthermore, we observed a negative Synechococcus spp. growth rate (-0.9 d–1) in the seagrass treatment, likely reflecting nutrient competition with the seagrass. Small-scale chambers proved to be a useful tool for studying the factors controlling spatial and temporal patterns of picoplankton across different habitats. Furthermore, future studies should examine picoplankton growth over a wider range of spatial scales in seagrass beds and adjacent unvegetated sediment.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

By introducing environmental mediator, for avoiding randomness in selecting indicators and subjectivity in deciding interaction path coefficients to reveal interaction mechanism among forest industry, ecology and environmental capacity, structural Pressure–State–Impact–Response (PSIR) and quantitative Structural Equation Modeling (SEM) are utilized with data on thirty–one provinces of China. We can find that: (i) forest industry has a negative influence on ecology, whereas ecology has a positive influence on industry; (ii) the destructive influence that industry has on ecology is much greater than the positive effect ecology has on industry; and (iii) environmental capacity plays a partial mediating role between industry and ecology. According to these results we can conclude that: (i) forest industry and ecology are not in a symbiotic relationship and have not reached a level of ecological security; (ii) the interaction between industry and ecology is in a period of transition from antagonistic to beneficial; and (iii) industry dominates ecology. However, we prospect the following advice: (i) methods of forest industry should be changed; (ii) new modes of industrial integration and circular economy should be developed; and (iii) the ability of the environment to sustain itself should be enhanced. The level of forest ecological security to discuss the symbiotic mechanism of industry and ecology will propose to be measured in future.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Dynamic time history analysis is a powerful and effective method to study the seismic response of tunnels, the dynamic time history to analyze the seismic response of the tunnel in the typical subway in this paper. The analysis results show that the overall levelling of the tunnel will not affect the tunnel too much, and the seismic response of the tunnel is mainly related to the relative displacement of the ground around the tunnel. The analysis results show that the internal force of the tunnel and the tunnel inclination have a good linear relationship, and the tunnel inclination can be used to measure the magnitude of the seismic response of the tunnel.

The carbonyl iron particles were dispersed in a polychloroprene rubber (CR) matrix under an external magnetic field for practical application as microwave absorption composites film. The film prepared under external magnetic field with a thickness of only 0.54 mm showed least reflection loss of -15.98 dB and the reflection loss value less than -10.0 dB over the frequency range of 11.4~14.8 GHz. In comparison with the microwave absorption properties of calculation by transmission line theory based on the tested relative complex permittivity and permeability and film prepared by general route without external magnetic field, the film made with external magnetic field exhibited more excellent microwave absorption properties, strongly depending on the increment of anisotropy and rearrangement of magnetic particles. The results indicated the composite film made under external magnetic field have excellent microwave absorption properties, which suggest that the composites thin film could be used as a thinner and lighter microwave absorber.

The aim of the present study was to investigate the incidence of breast (females), prostate, testicular and thyroid cancer in the Italian National Priority Contaminated Sites (NPCSs), served by cancer registries, where the presence of endocrine disruptors (EDs), reported to be linked to these tumors, was documented. Evidence of carcinogenicity of EDs present in NPCs was assessed based on evaluation by international scientific institutions/committees. Standardized Incidence Ratios (SIRs) were computed for each NPCS and cancer site with reference to the time window 1996-2005. Excess incidence of one or more cancer site at study was found in twelve out of fourteen NPCSs. Significantly increased SIRs were found for breast cancer in eight NPCSs, for prostate cancer in six, for thyroid cancer (both gender) in four and for testicular cancer in two. Non significantly increased SIRs were found in five NPCSs for testicular cancer and in two for thyroid cancer (males). Even if increased incidence of one or more cancer sites at study were found in several NPCSs, the ecological study design and the multifactorial etiology of the considered tumors do not allow reaching conclusions in terms of causal links with environmental contamination. In light of the observation of some excesses in SIRs, continuing epidemiological surveillance is warranted.

The necessity for precise and current data concerning the dynamics of land cover change in Indonesia is crucial for efforts to reduce natural vegetation cover due to agricultural expansion. The functionality of monitoring systems that incorporate Terra-MODIS is currently compromised by the limited availability of data for the immediate future. This study seeks to assess the potential of VIIRS satellite imagery in developing an early warning system for monitoring vegetation cover change in Indonesia. The Normalized Differential Open Area Index (NDOAI) computed from the 8-day’ VIIRS data was employed to detect changes in vegetation cover based on pixel-by-pixel subtraction in the NDOAI data time series. Evaluating the pixel-level accuracy of change detection is complicated due to the fact that we evaluate a change map at a coarser resolution than the Landsat-based reference map. The results revealed that increasing the threshold percentage is associated with improved accuracy. In change detection, there is often a trade-off between accuracy and sensitivity. A threshold that is too low may result in false positives, while a threshold that is too high may lead to missed changes. This study demonstrates that when a threshold value of less than 20% is applied, Landsat can identify vegetation cover changes at an earlier stage. Conversely, when a threshold value greater than 20% is employed, VIIRS will detect the change 4.5 days earlier than Landsat. Additionally, VIIRS is capable of detecting changes 25.4 days and 54.8 days faster than Landsat, respectively, when using thresholds of 40% and 75%.

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

The utilization of natural waxes to form oleogels has emerged as a new and efficient technique for structuring liquid edible oil into solid-like structures for diverse food applications. The objective of this study was to investigate the interaction between sunflower wax (SW) and monoglycerides (MGs) in olive oil oleogels and to assess their physical characteristics and storage stability. To achieve this, pure SW and a combination of SW with MGs in a 1:1 ratio were examined within a total concentration range of 6-12% w/w. The formed oleogels were characterized based on their microstructure, melting and crystallization properties, textural characteristics, and oxidative stability during storage. All the oleogels were shelf-stable, and as the concentration increased, the hardness of the oleogels also increased. The crystals of SW oleogels were long needle-like, while the combination of SW and MGs led to the formation of crystal aggregates and rosette-like crystals. The differential scanning calorimetry and FTIR showed that the addition of MGs led to different crystal structures. The oxidation results revealed that oleogels had low peroxide and TBARS values throughout the 28-day storage. These results provide useful insights about the utilization of SW and MGs oleogels for potential applications in the food industry.

Wildfires have always been a part of the history of Mediterranean forests. However, forest regeneration after a wildfire is not certain. It depends on many factors, some of which may be influenced by land management activities. Failure of regeneration will cause a regime shift in the ecosystem, reducing the provision of ecosystem services and ultimately leading to desertification. How can we increase Mediterranean forests’ resilience to fire? To answer this question, we did a literature review, investigating chains of processes that allow forests to regenerate (which we label “regeneration mechanisms”), and assessed the impact of selected management practices documented in the WOCAT database on the regeneration mechanisms. We identified three distinct regeneration mechanisms that enable Mediterranean forests to recover, as well as the time frame before and after a fire in which they are at work, and factors that can hinder or support resilience. The three regeneration mechanisms enabling a forest to regenerate after a fire consist of regeneration (1) from a seed bank; (2) from resprouting individuals; and (3) from unburned plants that escaped the fire. Management practices were grouped into four categories: (1) fuel breaks, (2) fuel management, (3) afforestation, and (4) mulching. We assessed how and under what conditions land management modifies the ecosystem’s resilience. The results show that land management influences resilience by interacting with resilience mechanisms before and after the fire, and not just by modifying the fire regime. Our analysis demonstrates a need for adaptive – i.e. context- and time-specific – management strategies.

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

Modular steel buildings (MSBs) interlocking inter-module connections (IMCs) have piqued researchers’ interest. However, the existing literature has not yet studied the optimisation of its plate thicknesses. This paper, therefore, focuses on optimising interlocking (IMCs) plate thickness in (MSBs), leveraging previous experimental and numerical simulation methodologies. Various numerical models for four MSBs interlocking (IMCs) with plate thicknesses (4 mm, 6 mm, 10 mm, and 12 mm) were developed under compression loading conditions. The study’s novelty lay in its comprehensive parametric analysis, which evaluated the slip phenomenon in (MSBs) connections and introduced a slip prediction model validated against empirical data. Further innovative machine learning approach was utilised to predict slip values based on applied force through a random forest regression model trained using the 'Treebagger' function. Sensitivity analysis and comparisons with alternative methods were utilised to underscore the reliability and applicability of the findings. The results showed that 11.03 mm was the optimal plate thickness for interlocking (IMCs) in modular steel buildings, with up to 8.08% reduced material costs. Increasing plate thickness boosts its deformation resistance by up to 50.75%. ‘TreeBagger’ random forest for anomaly detection and machine learning improves slip prediction up to 7% at higher force levels.

In mesoscale eddies, chemical properties and biological composition are different from those in surrounding water, due to their unique physical processes. It is unclear how physical-biological coupling occurs in warm-core eddies, particularly since no study has examined the relationship between bacteria and viruses. The purpose of the present study was to examine the influence of anticyclonic warm eddy on the relationship between bacterial and viral abundances as well as viral activity (viral production) in different depths. In the core of warm eddy, bacterial abundance (0.48 to 2.82 ×105 cells mL−1) fluctuated less than that of the outside eddy (1.12 to 7.03×105 cells mL−1). In particular, there was four-folds higher of viral-bacterial abundance ratio (VBR) estimated within the eddy below DCM than the outside eddy. We suggest that prevailing physical forces with downwelling at the center of the anticyclonic warm eddy, viruses can also be transmitted into the deep ocean directly through adsorption on particulate organic matter during sinking. Overall, our findings provide valuable insights into the interaction between bacterial and viral communities and their ecological mechanism within the warm eddy.

The influence of short term water absorption on the mechanical properties of halloysite nanotubes-multi layer graphene reinforced polyester hybrid nanocomposites has been investigated. The addition of nano-fillers significantly increased the flexural strength; tensile strength and impact strength in dry and wet conditions. After short term water exposure; the maximum microhardness; tensile; flexural and impact toughness values were observed at 0.1 wt% MLG. The microhardness increased up to 50.3%; tensile strength increased up to 40% and flexural strength increased up to 44%. Compared to dry samples; the fracture toughness and surface roughness of all types of produced nanocomposites were increased that may be attributed to plasticization effect. Scanning electron microscopy revealed that the main failure mechanism is caused by the weakening of nano-filler-matrix interface induced by water absorption. It was further observed that synergistic effects were not effective at concentration of 0.1 wt% to produce considerable improvement in mechanical properties of produced hybrid nanocomposites.

Volcanic activity essentially consists of the transfer of heat from the Earth’ interior to the surface. The precise signature of this heat transfer relates directly to the processes underway at and within a particular volcano and this can be observed, at a safe distance, remotely, using infrared sensors that are present on Earth-orbiting satellites. For over 50 years, scientists have perfected this art using sensors intended for other purposes, and they are now in a position to determine the particular sort of activity that characterizes different volcanoes. This review will describe the theoretical basis of the discipline and then discuss the sensors available for the task and the history of their use. Challenges and opportunities for future development in the discipline are then discussed.

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

Spectral characteristics of CDOM in water column are a key parameter for bio-optical modeling. Knowledge of CDOM optical properties and spatial discrepancy based on the relationship between water quality and spectral parameters in Yinma River watershed with in situ data collected highly-polluted waters are exhibited in this study. Seasonal field data sets collected over a period of 2 months in 2015 in Yinma River Watershed. Based on the comprehensive index method, the riverine waters showed serious contamination, especially the COD, Fe, Mn, Hg and DO were out of range contamination warning. Dissolved organic carbon (DOC) and total suspended matter (TSM) with prominent non-homogenizing were significantly high in the riverine waters, but chlorophyll-a (Chl-a) was opposite. Ternary phase diagram showed that non-algal paritcles absorption played an important role in total non-water light absorption (>50%) in most sampling locations, and mean contribution of CDOM were 13% and 22% in summer and autumn respectively. Analysis of ratio of absorption at 250-365 nm (E_250:365) and spectral slope (S_275-295) indicated that CDOM had higher aromaticity and molecular weight in autumn than in summer, is consistent with the results of water quality and relative contribution. Redundancy analysis (RDA) indicated that the environmental variables OSM had a strong correlation with CDOM absorption, followed by heavy metal, e.g., Mn, Hg and Cr⁶⁺. However, for the specific UV absorbance (SUVA₂₅₄), the seasonal values showed opposite results compared with the reported literature. The potential reasons were the more UDOM (uncolored Dissolved Organic Matter) from human source (wastewater effluent) existed in waters. Terrigenous inputs simultaneously are in relation to the a_CDOM(440)-DOC relationship with the correlation coefficient was 0.90 in summer (2-tailed, p<0.01), and 0.58 in autumn (2-tailed, p<0.05). Spatial distribution of CDOM parameters exhibited that the downstream regions focused on dry land have high CDOM molecular weight and aromatic hydrocarbon. Partial sampling locations around the cities or countries generally showed abnormal values due to terrigenous inputs. As a bio-optical model parameter, spectral characteristic of CDOM is helpful in adjusting the derived algorithms in highly-polluted environments. The study on organic carbon and pollutants in highly-polluted waters had an important contribution to global carbon balance estimation and water environment protection.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

The decarbonization of the built environment, both in new construction and renovation, is crucial to mitigate its relevant impact on climate change and achieve the Paris agreement goals. This study presents a systematic LCA-based methodology to assess the whole life carbon emissions of buildings, applied to a proposal for the regeneration of one of Milan’s disused railway yards. As an entry for the 2020 Reinventing Cities competition, Scalo Lambrate is a project for a mainly residential neighborhood with a public park. Strategies to reduce carbon emissions deriving both from the operational energy and construction and maintenance were evaluated and their effects compared to a reference scenario over a time horizon of 100 years. The results show that, while the opportunities to reduce carbon emissions during the use phase are somehow limited due to the already stringent performance requirements for new builds, the use of fast-growing biogenic materials for construction materials, even if mixed with more traditional ones, can provide a significant reduction of the global warming potential over the whole life cycle, with a reduction of 70% over the baseline. The remaining emissions can be offset with afforestation initiatives that, however, must be assessed against land use issues.

(1) Background: A simple approach to map irrigated landcover has been introduced by using measures derived from optical spectral range as an alternative to thermal range. It has been demonstrated that substituting surface temperature (Ts, ‘thermal approach’) with SWIR transformed reflectance (STR, ‘optical approach’) to detect surface moisture is feasible with comparable results. (2) Methods: Using an iterative thresholding procedure to minimize within-class variance, the bilevel segmentation of variables derived from Landsat-8 representing surface moisture and vegetation cover was achieved for the 2020-21 summer for a key irrigation district in Australia. (3) Results: The results of irrigated landcover by optical approach found to be comparable with those by thermal approach. The classification accuracy was assessed using water delivery records at farm level. Though the overall accuracy is high in both cases, the optical approach (97.6%) performed slightly better than the thermal approach (93.9%). (4) Conclusions: The feasibility of using STR to map irrigated landcover has been confirmed by a high-level overall accuracy assessment. This has broader implications in terms of irrigated landcover assessment, as the use of satellite imagery in these applications may not necessarily be limited to microwave or thermal sensors.

Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.

Antimony (Sb) has gained significance as a critical raw material (CRM) within the European Union (EU) due to its strategic importance in various industrial sectors, particularly in the textile industry for flame retardants and as a component of Sb-based semiconductor materials. Moreover, Sb is emerging as a potential alternative for anodes used in lithium-ion batteries, a key element in the Energy transition. This study focused on exploring the feasibility of identifying and quantifying Sb mineralizations through the spectral signature of soils using reflectance spectroscopy, a non-invasive remote sensing technique, and by employing deep learning algorithms such as Convolutional Neural Networks (CNNs). Common signal preprocessing techniques were applied to the spectral data, and the soils were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Despite achieving high R-squared values, the study faces a significant challenge of generalization of the model to new data. Despite the limitations, this study provides valuable insights into potential strategies for future research in this field.

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

Our tissues usually have just the right number of cells to optimally fulfil their function. Not enough cells within a tissue can lead to dysfunction, while too many cells result in a tumour. Yet, how this homeostatic balance is maintained remains poorly defined. Most differentiated cells within tissues have a finite lifespan and need to be replaced at a corresponding pace to maintain tissue homeostasis. These new differentiated cells are generated by proliferation of the stem/progenitor cells that serve the tissue. Work in simple invertebrates clearly suggests stem cells respond to at least two types of signals: niche signaling and growth factors. Niche signals promote the undifferentiated state by preventing differentiation, and thus allow for stem cell self-renewal. Growth factor sources comprise a systemic input reflecting the animal’s nutritional status, and a localized, homeostatic feedback from the tissue that the stem cells serve. That homeostatic signal couples stem cell proliferation rates to the tissue’s need for new differentiated cells. Evidence from simple organisms suggests two types of benign tumours can arise from deregulation of either niche or homeostatic signaling. Namely, constitutive niche signaling promotes the formation of undifferentiated “stem cell” tumours, while defective homeostatic signaling leads to the formation of differentiated tumours. We propose that these principles may be conserved and underlie benign tumour formation in humans, while benign tumours can evolve into cancer.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH^high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

Managing Water, Energy, and Food (WEF) resources within socio-environmental systems demands innovative strategies that provide decision-makers with actionable insights. This article explores the challenges and potential solutions of employing Focus Maps and choremes as a novel approach for assessing anthropogenic impacts and enhancing the visualization of the WEF Nexus in specific geographic areas. By integrating geospatial data, multi-criteria analysis, and involving stakeholders, our research aims to develop Choreomatic Focus Maps (CFMs) that offer a comprehensive spatial representation of the WEF Nexus, facilitating better-informed decision-making at the community level. Our current work outlines visualization of WEF Nexus, as an initial stages of creating CFMs through a detailed step-by-step process. This includes identifying the main drivers for WEF nexus, such as anthropogenic activities and their distribution, evaluating environmental factors, linking anthropogenic impact with environmental indicators over time, and conducting on-site validation. Our focus is on advancing through these crucial steps, particularly emphasizing field validation within the Local Decision-Makers Tools, visualized here by using Focus Maps. This phase is vital for ensuring our approach is grounded in reality and meets the needs of the communities within the Danube Delta region. By doing so, we aim to provide a visual summary of the WEF Nexus that not only captures the complexity of this fragile ecosystem but also incorporates local insights and priorities, identifying key areas where human activities have significant impacts.

The therapeutic, attenuative, and morphological effects of proprietary neural stem cell-derived extracellular vesicles (NSC EVs, AB126) produced by Aruna Bio, Inc. were assessed in a range of in vitro and in vivo models of stroke. We emphasize that modulation of neuroinflammation is a key target and suggest further studies to advance our understanding of the mechanisms of action and ultimately how best to dose and monitor the benefits of AB126 in stroke patients.

The analysis and simulation of water quality in distribution networks is a complex issue of great concern today. The analysis of the evolution of water age, as a simple indicator of water quality in the network, is of great interest in both design and operation phases. Understanding the factors that have the strongest influence on water quality is key to developing adequate strategies aimed at preserving it. This paper firstly analyses the factors with biggest influence in the tanks water age, to support the selection of the most appropriate configuration from the point of view of water quality during design phases. Then, the main considerations when modelling tanks following the different mixing models considered in Epanet have been presented. Also, a real tank behaviour has been characterised through field measurements and Epanet simulations in order to determine the best fitted mixing model.

A novel educational platform called Shared Modeling and Simulation Environment (SMSE) was initiated in the ERASMUS+ “CybPhys” project. It integrates the Jupyter platform, including Ju-pyter Notebooks, for e-learning in the STEM field. A novel platform enhances e-learning by combining Moodle with Jupyter's capabilities to create virtual labs. A survey was conducted in the spring of 2023 among bachelor and master students of Chernihiv National Polytechnic Uni-versity aimed to gather feedback from students using SMSE in their e-learning process. Two student groups were involved: one of them consisted of students using SMSE in both the autumn and spring semesters and another represented the students starting with SMSE in the spring se-mester. The survey based on the adjusted Technology Acceptance Model (TAM) was conducted to understand the acceptance of this e-learning approach. A comprehensive analysis of students’ answers based on the TAM approach revealed the inside of the process of transformation of stu-dents’ perceptions during the acquisition of the SMSE platform. Our research demonstrates that SMSE effectively merges Moodle's online learning capabilities with Jupyter notebooks, provid-ing a flexible and interactive learning experience for both in-class and remote students. It pro-vides a web-based, multifunctional e-learning environment that combines a variety of tools and technologies, giving students the possibility to be involved in all sorts of teaching activities, such as lectures, exercises, simulations, etc., through the use of one single online environment.

Improper disposal of waste plastic has caused serious ecological and environmental pollution problems. Transforming plastics into high value-added chemicals can not only achieve efficient recycling of waste plastics, but also an effective way to control white pollution. The catalyst selectively breaks the C-C bond of polyolefin plastic under heat treatment and converts it into liquid fuel, thus realizing sustainable recycling of plastics and has a good development prospect. This review provides a detailed overview of the current development of catalytic pyrolysis, catalytic hydrolysis, solvent decomposition and supercritical hydrothermal liquefaction for cracking plastics to make fuel oil. The reaction mechanism, influencing factors and promoting effects of catalysts in various degradation technologies are analyzed and summarized and the latest proposed tandem reaction for degrading plastics is briefly introduced. Finally, some optimization paths of waste plastic pyrolysis to fuel oil technology are proposed: synergies between mixed raw materials, in-depth exploration of catalysts, design and manufacture of reactors that match the pyrolysis technology. All these are important research directions for promoting the industrialization of plastic pyrolysis to fuel oil.

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (p&lt;0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data shows that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy.

In this study, the causal-effect between carbon dioxide emissions and forestry production and trade was investigated in Ghana by employing a data spanning from 1961 to 2014 by using the VECM and ARDL model. Evidence of the long-run equilibrium relationship in the VECM shows that, a 1% increase in veneer sheet production reduces carbon dioxide emissions by 1.47% in the long-run. There was evidence of a bidirectional causality between carbon dioxide emissions and veneer sheet production, carbon dioxide emissions and wood charcoal production, and a unidirectional causality running from carbon dioxide emissions to wood fuel production and plywood production to carbon dioxide emissions. Evidence from the long-run equilibrium relationship in the ARDL model shows that; a 1% increase in plywood production will increase carbon dioxide emissions by 0.17% in the long-run, a 1% increase in sawnwood production will increase carbon dioxide emissions by 0.17% in the long-run, a 1% increase in wood charcoal production will increase carbon dioxide emissions by 0.36% in the long-run and a 1% increase in wood fuel production will increase carbon dioxide emissions by 0.37% in the long-run.

In this study, an attempt was made to investigate the Kenya case of multivariate causality of carbon dioxide emissions by employing a time series data spanning from 1961-2011 using the ARDL method of cointegration analysis. The long-run elasticities show that, a 1% increase in financial development increases carbon dioxide emissions by 0.28%, a 1% increase in GDP per capita increases carbon dioxide emissions by 1.32% and a 1% increase in urbanization decreases carbon dioxide emissions by 1.14%. There was a unidirectional causality running from financial development, food production index, GDP per capita, industrialization and urbanization to carbon dioxide emissions. The innovation accounting shows that 20% of future shocks in carbon dioxide emissions are due to fluctuations in financial development, 9% of future shocks in financial development are due to fluctuations urbanization and 22% of future shocks in food production index are due to fluctuations in carbon dioxide emissions.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

The research on the excavation mechanical properties of underpass tunnels has already had certain results, but fewer of them consider the effects of dynamic and static loads on the excavation mechanical properties of underground tunnels at the same time, especially the lack of research cases of double-line highway tunnels with angled underpasses of existing railway tunnels. In this paper, based on the tunnel project of the new double-line Shiqian Highway Tunnel passing under the Hurong Railway at an oblique angle, the mechanical parameters of the rock body in the cross-tunneling area under the influence of static and dynamic load coupling are obtained by using the disturbance quantification coefficients and the Hoek-Brown criterion based on the method of over-advanced geological prediction and the investigation of the surrounding rock on the palisade face, and the engineering-scale finite element model is constructed and the mechanical characteristics of the excavation in the tunnel of the double-lane highway tunnel passing under the existing railroad under the influence of the static and dynamic loads are analyzed. The results show that: the new tunnel rock movement law for the top of the arch sinking, bottom plate bulging, side wall to move outward, the height and width of the arch and bottom plate arch with the tunnel excavation and increase, the side wall rock displacement effect is smaller; left and right lines of the tunnel disturbed area of the rule of change is similar; the existing tunnel bottom plate displacement is more than the top plate and the left and right side walls by the excavation of the time step influence is larger. Typical profile displacement is mainly determined by the distance from the excavation surface; the new tunnel in the four types of calculation conditions of the rock disturbance angle is the same; the existing tunnel roof and side wall Von Mises stress extreme occurs in the tunnel structure, the bottom plate there are pressure relief and pressure-bearing areas; based on the displacement control criteria, the recommended upper and lower step blasting method.

Climate change is challenging the agricultural sector worldwide. The pressure exerted by the altered thermal conditions drives the zonal shift for various cultivations. This study presents the multiyear analysis of the Growing Degree Days (GDD) index over the Northern Mediterranean Basin (NMB), focused on the high-value vine cultivation derived from the E-OBS dataset. To handle this extensive environmental dataset, R-language scripts and packages were applied, along with the capabilities of the GIS software. The investigated time period spans from 1969 to 2018, and the performed analysis indicates a broad shift/expansion in areas of GDD exceeding 2000 heat units. The extracted results specify the viticultural areas where the GDD index surpasses the suitable values for vine cultivation, owing to the increase of the thermal stress risk. In addition to mapping areas with GDD ≥ 2000, spatial calculations of the surface of areas meeting this criterion per country in the study area were made. In the northern parts of the NMB, the rise of the GDD index values indicates the establishment of vine plantations in the future.

There is a need to find methods to intensify the anaerobic digestion process. One possibility is the use of pre-treatment techniques. Many laboratory tests confirm their effectiveness, but in most cases, there is no verification work carried out on industrial plants. The aim of the research carried out under laboratory conditions and on a large scale was to determine the technological and energy efficiency of the use of hydrodynamic cavitation in the pre-treatment of a waste mixture from dairy farms. It has been shown that hydrodynamic cavitation significantly increases the concentration of organic compounds in the dissolved phase. In the most effective variants, the increase in the content of these indicators was over 90% for both COD and TOC. The degree of solubilisation achieved was 49±2.6% for COD and almost 52±4.4% for TOC. Under laboratory conditions, the highest effects of anaerobic digestion were achieved after 10 minutes of pre-treatment. The amount of biogas was on average 367±18 mL/gCOD and the amount of methane 233±13 mL/gCOD. Further large-scale optimisation trials showed that after 8 minutes of hydrodynamic cavitation, the biogas yield was 327±8 L/kgCOD with a CH4 content of 62.9±1.9%. With this variant, the net energy yield was 66.4±2.6 kWh/day, a value that was 13.9% higher than the original variant with 10 minutes of disintegration and 3.1% higher than the variant without pre-treatment.

According to the ECCB, cancer represents the transition of a genomically damaged multicellular cell to a lower level of cell organization, controlled by the ancestral gene regulatory network (GRN) from the ancestral compartment of human and metazoan genomes. Cancer adopts ancient mechanisms and rules of the common ancestor, similar to those observed in parasitic amoebae. In cancer, the productive cell line generating CSCs is a non-gametogenic cancer germline. This germline proliferates through asymmetric cell division (ACD phenotype). CSCs lack proliferative capacity; they persist in hypoxic niches in a quiescent cell state or transition to an amplifying cell state that performs cyst-like polyploidization cycles, giving rise to precursors and CSCs capable of differentiation. Malignization arises from genomically dysfunctional tetraploid germline cells (DSCD phenotype) that proliferate in a precancerous stage through symmetric cell cycles. DSCD progeny undergo homotypic fusion, forming multinucleated genome repair syncytia (MGRS pathway) driving carcinogenesis. During tumorigenesis, metastasis, and recurrence, subsequent germline clones initiate a cascade of increasingly pathogenic CSCs through mechanisms such as heterotypic cell fusion, soma-to-germ transition, and polyploid giant cell structures (PGCCs). Irradiation and chemotherapies drive some of the very few surviving but dysfunctional CSCs through a PGCC repair pathway homologous to the MGRS pathway of carcinogenesis. The large number of PGCCs during metastasis and recurrence results from the perpetual germline cell damage and CSC poverty induced by oxygen levels above 6.0% O2 (germline hyperoxia).

Alternative fertilizations are essential to minimize the deteriorating effects of chemical fertilizers on soil and water quality/health. Accordingly, the present work investigated the effects of combined organic-inorganic fertilization (COIF) on wheat and rice yields, soil nutrients, and soil Cd accumulation. Hence, seven different treatments were set up: control (CK); conventional fertilization (CF); optimized fertilization (OF); organic fertilizer replacing 25% (T1) and 50% (T2) of OF; and organic nitrogen (N) replacing 25% (M1) and 50% (M2) of OF-N. Overall, significant increases occurred in the yields of COIF crops. Compared with the CF, the highest wheat and rice yields happened in M1 treatment (approximately by18.5%) (P &lt; 0.05). COIF slightly alleviated soil acidification, and improved the cation exchange capacity (CEC) of the study soils. Besides, COIF treatments significantly increased the contents of total phosphorus, total potassium, available phosphorus, and available potassium by 6.35 to 16.9 %, 3.17 to 10.9 %, 5.53 to 28.7 %, and 2.6 to 12 %, respectively (P &lt;0.05). Nevertheless, negligible increases took place in Cd content of COIF soils compared with the CK. Altogether, our results concluded on 25% replacement of OF-N by organic N (M1) to effectively improve the fertility/ecological sustainability of the study soils.

The Tibetan Plateau(TP) is known as ‘the water tower of Asian’, its precipitation variation play an important role in the eco-hydrological processes and water resources regimes. based on the monthly mean precipitation data of 65 meteorological stations over the Tibetan Plateau and the surrounding areas from 1961-2015,variations, trends and temporal-spatial distribution were analyzed, furthermore, the possible reasons were also discussed preliminarily. The main results are summarized as follows: the annual mean precipitation in the TP is 465.54mm during 1961-2015, among four seasons, the precipitation in summer accounts for 60.1% of the annual precipitation, the precipitation in summer half year (May.- Oct.) accounts for 91.0% while that in winter half year (Nov.- Apr.) only accounts for 9.0%; During 1961-2015, the annual precipitation variability is 0.45mm/a and the seasonal precipitation variability is 0.31mm/a, 0.13mm/a, -0.04mm/a and 0.04mm/a in spring, summer, autumn and winter respectively on the TP; The spatial distribution of precipitation can be summarized as decreasing from southeast to northwest in the TP, the trend of precipitation is decreasing with the increase of altitude, but the correlation is not significant. The rising of air temperature and land cover changes may cause the precipitation by changing the hydrologic cycle and energy budget, furthermore, different pattern of atmospheric circulation can also influence on precipitation variability in different regions.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

The Double U-pipe ground heat exchanger, recognized for its straightforward process, cost-effectiveness, high heat exchange efficiency, and low thermal resistance, stands as the predominant ground heat exchanger type in today's shallow geothermal energy development and utilization. Recent years have seen significant research into the heat transfer influencing factors and heat exchange performance of Double U-pipe ground heat ex-changers via experimental testing methods. Yet, studies integrating numerical simulation with in-situ testing have been less frequent. Drawing on the cylindrical heat source model theory and the outcomes of regional in-situ thermal response tests, this paper develops a Double U-pipe ground heat transfer model by establishing physical, mathematical, and heat transfer geometric models. It assesses the impact of varying inlet temperatures, flow rates, and initial ground temperatures on heat exchange efficiency under heating conditions. The results validate the precision of the double U-pipe ground heat exchanger model based on in-situ testing. They show that enhancing the temperature differential between the inlet and initial temperatures, elevating the initial ground temperature, and moderately increasing the flow rate can boost the system's heat exchange efficiency.

Adult stem cells (ASCs) can be cultured with difficulty from most tissues, often requiring chemical or transgenic modification to achieve adequate quantities. We show here that mouse primary fibroblasts grown in suspension change from the elongated and flattened morphology observed under standard adherent culture conditions generating rounded cells with large nuclei and scant cytoplasm expressing the mesenchymal stem cell (MSC) marker (Sca1; Ly6A) within 24hrs. Based on this initial observation, we describe here a suspension culture method that, irrespective of the lineage used, mouse fibroblast, primary human somatic cells (fibroblasts, hepatocytes and keratinocytes), is capable of generating a high yield of cells in spheroid form which display expression of ASCs surface markers, circumventing the anoikis which often occurs at this stage. Moreover, mouse fibroblasts-derived spheroids can be differentiated into adipogenic and osteogenic lineages. Analysis of single cell RNA sequence data identified 8 distinct cell clusters with one in particular comprising approximately 10% of the cells showing high levels of proliferative capacity expressing high levels of genes related to MSCs and self-renewal as well as extracellular matrix (ECM). We believe the rapid, high-yield generation of proliferative, multi-potent ASC-like cells by the process we term suspension-induced stem cell transition (SIST) could have significant implications for regenerative medicine.

The objective of this study was to determine how application with dolomitic limestone and grazing type (continuous or deferred) affect sheep grazing location and feed preference when the pasture growth rate is maximum. A 4ha field was divided into 4 plots: P1 and P2- without application of dolomitic limestone, continuous (CG) and deferred grazing (DG), respectively; P3 and P4- with application of dolomitic limestone, DG (1AUE), and CG (2.4 AUE), respectively. In DG, animals were placed and removed from the plots depending on the height of the pasture. In each plot, 12 georeferenced sampling points were identified. Throughout the pasture's vegetative cycle (autumn, winter, spring, and early summer) several measurements of pasture height and cut were carried out. From the beginning of March to the beginning of June, animal behavior was observed, by trained observers, through binoculars on six dates. Animals' activity grazing and location was recorded. The results show that: (i) the application of dolomitic limestone combined with CG provided higher values of pasture height; (ii) there were no significant differences in pasture quality between treatments; (iii) Deferred grazing led to 50% more sheep grazing days than continuous grazing; (iv) there were no significant differences in soil compaction between CG and DG; (v) the type of grazing and the treatment with dolomitic limestone did not seem to change the grazing pattern between treatments. This work contributes to understanding the relationships between different types of grazing in dryland pastures, with and without application of dolomitic limestone, and preferred grazing locations for sheep. This work could help agricultural managers make more informed decisions with the aim of promoting the sustainable intensification of livestock production in the Montado ecosystem.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the widely practiced treatment; however, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to high blood glucose level. However, determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for treatment of diabetes is still debated upon. While hPSC-derived beta cells are perceived as the ultimate candidate, the efficiency needs further improvement in order to obtain a sufficient number of glucose responsive β-cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address co-generation of functionally relevant islet cell subpopulations and structural properties contributing to glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM_2.5-₁₀) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM_2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM₁₀ decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG. Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27/CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21/CDKN1A(Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1/PREF1. Furthermore, NANOG induced downregulation of DNMT1, a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.

Heavy metal pollution poses a significant threat to ecosystems and human health worldwide. In response to this pressing issue, bioremediation has emerged as a promising approach for mitigating contamination. This paper adopts a bibliographic method to explore the key techniques and applications of bioremediation. Furthermore, we delve into the most prominent threats to human environmental health and the corresponding remediation methods. Additionally, we discuss the future trajectory of bioremediation research, with a particular focus on the integration of big data and machine learning technologies. These advanced methodologies hold great potential for enhancing the effectiveness and efficiency of environmental remediation efforts in the face of escalating pollution challenges.

The long-term use of fertilizers and pesticides in conventional cultivation has resulted in a decrease in soil productivity and vegetable yields in greenhouses. However, only a limited number of studies have explored the impacts of organic cultivation on greenhouse soil. Specifically, there is a scarcity of research examining the alterations in soil aggregate mediated organic carbon and microbial communities, which are known to enhance soil productivity. This study investigated the properties of soil aggregates, including the levels of organic carbon fractions, microbial community, and enzyme activity with the three aggregate classes microaggregates (&lt;0.25 mm), small macroaggregates (2-0.25 mm) and large macroaggregates (&gt;2 mm). These investigations were conducted under three different cultivation methods in a greenhouse: conventional cultivation (CC), integrated cultivation (IC), and organic cultivation (OC) in greenhouse. The results showed that (1) OC and IC promoted the formation of small macro-aggregates and enhanced aggregate stability compared to CC, (2) SOC in the three size fractions of OC increased by 98.99%-92.06% compared to CC; EOC increased by 98.47%-117.59%; POC increased by 138.59%-208.70%; MBC increased by 104.71%-230.61%; DOC increased by 21.93%-40.90%, respectively; (3) Organic cultivation significantly increased enzyme activity in all three particle size aggregates and increased the relative abundance of bacteria in micro-aggregates as well as the relative abundance of fungi in small macro-aggregates. Structural equation model (SEM) analysis revealed that organic farming practices fostered the development of smaller macro-aggregates, elevated microbial and enzyme activities within soil aggregates, and facilitated the conversion of soil nutrients and carbon sequestration. consequently, this led to an increase in soil organic carbon content and improved vegetable yield in greenhouse environments. In conclusion, the soil carbon content and vegetable yield are enhanced through long-term organic cultivation in greenhouses, primarily by increasing the proportion of small macro-aggregates.

The variation of aerosols, especially dust aerosol, in time and space plays an important role in climate forcing studies. Aerosols can effectively reduce land surface longwave emission and re-emit energy at a colder temperature, making estimation of downwelling surface longwave radiation (DSLR) with satellite data difficult. Using the latest atmospheric radiative transfer code (MODTRAN 5.0), we simulate the outgoing longwave radiation (OLR) and DSLR under different land surface and atmospheric profile conditions. The results show that dust aerosol has an obvious “warming” effect to longwave radiation compared with other aerosols, that aerosol longwave radiative forcing (ALRF) increased with increasing aerosol optical depth (AOD), and that the atmospheric water vapor content (WVC) is critical to the understanding of ALRF. A method is proposed to improve the accuracy of DSLR estimation from satellite data for the skies under heavy dust aerosols. The AOD and atmospheric WVC under cloud-free conditions with a relatively simple satellite-based radiation model that yields the high accurate DSLR under heavy dust aerosol are used explicitly as model input to reduce the effects of dust aerosol on the estimation of DSLR. Validations of the proposed model with satellites data and field measurements show that it estimates the DSLR accurately under heavy dust aerosol skies. The root mean square errors (RMSEs) are 20.4 W/M² and 24.2 W/M² for Terra and Aqua satellites, respectively, at the Yingke site, and the biases are 2.7 W/M² and 9.6 W/M², respectively. For the Arvaikheer site, the RMSEs are 23.2 W/M² and 19.8 W/M² for Terra and Aqua, respectively, and the biases are 7.8 W/M² and 10.5 W/M², respectively. The proposed method is especially applicable to acquire relatively high accurate DSLR under heavy dust aerosol using MODIS data with available WVC and AOD data.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

In recent decades, as eutrophication in inland and coastal waters (ICWs) has increased due to anthropogenic activities and global warming, so has the need for timely monitoring. Compared with traditional sampling and laboratory analysis methods, satellite remote sensing technology can provide macro-scale, low-cost, and near real-time water quality monitoring services. The Geostationary Ocean Color Imager (GOCI), integrated onboard the Communication Ocean and Meteorological Satellite (COMS) from the Republic of Korea, was the first geostationary ocean color observation satellite and was operational from April 1, 2011 to March 31, 2021. Over ten years, GOCI has observed oceans, coastal waters, and inland waters within its 2,500 km×2,500 km target area centered on the Korean Peninsula. The most attractive feature of GOCI, compared with other commonly used watercolor sensors, was its high temporal resolution (1h, eight times daily from 0 UTC to 7 UTC), providing the opportunity to monitor the quality of ICWs, where optical properties can change rapidly throughout the day. This systematic review aims to comprehensively review GOCI features and applications in ICWs, analyzing progress in atmospheric correction algorithms and water quality monitoring. Analyzing 123 articles from the Web of Science and China National Knowledge Infrastructure (CNKI) through a bibliometric quantitative approach, we examined GOCI’s strength and performance with different processing methods. These articles reveal that GOCI played an essential role in monitoring the ecological health of ICWs in its observation area in East Asia. GOCI has led the way to a new era of geostationary ocean satellites, providing new technical means for monitoring water quality in oceans, coastal zones, and inland lakes. We also discuss the challenges encountered by geostationary satellites in monitoring water quality and provide suggestions for improvements.

This paper describes the first results of an Image Recognition Based Location (IRBL) for mobile application focusing on the procedure to generate a Database of range images (RGB-D). In an indoor environment, to estimate the camera position and orientation, a prior spatial knowledge of the surrounding is needed. In order to achieve this objective a complete 3D survey of two different environment (Bangbae metro station of Seoul and E.T.R.I. building in Daejeon – Republic of Korea) was performed using LiDAR (Light Detection And Ranging) instrument and the obtained scans were processed in order to obtain a spatial model of the environments. From this, two databases of reference images were generated using a specific software realized by the Geomatics group of Politecnico di Torino (ScanToRGBDImage). This tool allow to generate synthetically different RGB-D images) centered in the each scan position in the environment. Later, the external parameters (X, Y, Z, ω, φ, κ) and the range information extracted from the DB images retrieved, are used as reference information for pose estimation of a set of acquired mobile pictures in the IRBL procedure. In this paper the survey operations, the approach for generating the RGB-D images and the IRB strategy are reported. Finally the analysis of the results and the validation test are described.

Background: Extracellular Vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties, clinical and therapeutical applications, even towards cancer. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates the cancer’s growth and spread. Methods: The most valuable and significant PubMed Literature about extracellular vesicles and adipose–derived stem cells exosomes was selected and analyzed in order to report their biological properties and potential applications, in particular on the Triple–Negative Breast Cancer. Results: Adipose–derived stem cells exosomes represent a potential tool to target the tumor core of the Triple–Negative Breast Cancer, its microenvironment and surrounding tissues including metastasis. The authors are developing a supportive Triple–Adipose–derived stem cells Exosomes [T.A.E.] Technology against breast cancer in order to perform a selective preconditioning of the cancer before or while the traditional oncological treatments are running. Conclusion: The possibility to exploit the impact of Adipose–derived stem cells exosomes within the T.A.E. Technology against the Triple–Negative breast cancer is real, highlighting a new era for supportive measures against breast cancer.Keywords: Extracellular vesicles; Exosomes; Adipose–derived stem cells, Tumor microenvironment, Triple–Negative Breast Cancer, T.A.E. Technology.

Background: Chronic Back Pain due to Facet Joint Syndrome is a common and debilitating con-dition. Advances in regenerative medicine have shown that Autologous Unmodified Adipose Tissue-Derived Regenerative Cells (ADRC) provide several beneficial effects [1,2]. These regen-erative cells can differentiate into various tissues [3] and exhibit a strong anti-inflammatory po-tential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient´s abdominal fat. Methods: We report long-term results of 37 patients (age 31-78 years, mean 62.5) suffering from “Facet Joint Syndrome” The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then liposuction was performed. 50-100 cc of fat were harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at one week 1 and 5 years. Results: Every patient reported improved VAS pain at any follow-up (1 week, 1, and 5 years) with ADRCs compared to the baseline. Conclusion: Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved quality of life in the long term.

Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4 and c-MYC in all samples while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n=6) and reverse-transcription quantitative polymerase chain reaction (n=5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of four primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

Background: Developing an efficient and standardized method to isolate and characterize adipose-derived stem cells (ASCs) from the stromal vascular fraction (SVF) of the adipose tissue for clinical application represents one of the major challenges in cell therapy and tissue engineering. Methods: In this study, we proposed an innovative, non-enzymatic protocol to collect clinically useful ASCs within freshly isolated SVF from adipose tissue by centrifugation of the infranatant portion of lipoaspirate and to determine the characteristic cytofluorimetric pattern, prior to in vitro culture. Results: The SVF yielded a mean of 73,32 \pm\ 10,89% cell viability evaluated with CALCEINA-FITC, i.e. cell-permeant dye. The ASCs were positive for PC7-labeled mAb anti-CD34 and negative for both PE-labeled mAb anti-CD31 and APC-labeled mAb anti-CD45. The frequency of ASCs estimated according to the panel of cell surface markers used was 51,06%\ \pm 5,26% versus the unstained ASCs subpopulation that was 0,74%\pm0,84% (P<0.0001). The ASCs events/\muL were 1602,13/\muL \pm 731,87/\muL. Conclusion: Our findings suggested that ASCs found in freshly isolated adipose SVF obtained by centrifugation of lipoaspirate can be immunophenotypically identified with a basic panel of cell surface markers. These findings aimed to provide standardization and contribute to reducing the inconsistency on reported cell surface antigens of ASC derived from the existing literature.

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was significantly increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

Buerger's disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.

The shortage of donor organs is a major global concern. Organ failure requires the transplantation of functional organs. Organ donors are preserved in warm or cold ischemia. Ischemia and reperfusion damage the organs, due to the lack of oxygen during the ischemia step and the oxidative stress during the reperfusion step. Different methodologies were developed to prevent or diminish the level of injuries. Preservation solutions were first developed, followed by the addition of chemical compounds. In addition of inhibitors of mitogen activated protein kinase, inhibitors of the proteasome, mesenchymal stem cells started to be used 13 years ago to prevent or diminish the organ’s injuries. Mesenchymal stem cells (e.g bone marrow stem cells, adipose derived stem cells) have proven to be powerful tools in repairing damaged organs. This review will focus on the use of some bone marrow stem cells, adipose derived stem cells and umbilical cord stem cells on preventing or decreasing the injuries due to ischemia-reperfusion.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

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

The collapsible loess will rapidly soften and lose its bearing capacity when soaked in water. Under a mild condition (20°C), the biomimetic inorganic agent, Diammonium phosphate (DAP), reacts with calcite in the collapsible loess, producing a stronger bonding material, hydroxyapatite (HAP), to modify and stabilize the soil. Uniaxial compression, permeability tests and morphological analysis using XRD and SEM/EDX microscopy were carried out to assess the effectiveness of DAP stabilization on the collapsible loess. The results indicated that HAP improved the inter-particle bonding within loess, filled the pores within particles, reduced the permeability, and consequently mitigated collapsibility of loess. The compressive strength of DAP-treated loess increased as DAP concentration increased. Following 28-days curing, the compressive strength of the loess treated with a 3.0 mol/L DAP solution was six times greater than that of the untreated group. DAP's reinforcement effect on loess was superior to that of cement. The compressive strength of DAP-treated loess was about double that of cement-treated loess and the permeability coefficient was reduced by more than 50% at equivalent solid content. Furthermore, DAP generated 68% fewer carbon emissions compared to Portland cement. Considering eco-friendly and sustainable development, DAP offers a more competitive alternative for modification and stabilization of loess.

Plant leaf area index (LAI) is a key characteristic affecting field canopy microclimate. In addition to traditional professional measuring instruments, smartphone camera sensors have been used to measure plant LAI. However, when smartphone methods were used to measure conifer forest LAI, very different performances were obtained depending on whether the smartphone was held at the zenith angle or at a 57.5° angle. To validate further the potential of smartphone sensors for measuring conifer LAI and to find the limits of this method, this paper reports the results of a comparison of two smartphone methods with an LAI-2000 instrument. It is shown that both methods can be used to reveal the conifer leaf-growing trajectory. However, the method with the phone oriented vertically upwards always produced better consistency in magnitude with LAI-2000. The bias of the LAI between the smartphone method and the LAI-2000 instrument was explained with regard to four aspects that can affect LAI: gap fraction, leaf projection ratio, sensor field of view (FOV), and viewing zenith angle (VZA). It was concluded that large FOV and large VZA cause the 57.5° method to overestimate the gap fraction and hence underestimate conifer LAI, especially when tree height is greater than 2.0 m. For the vertically upward method, the bias caused by the overestimated gap fraction is compensated for by an underestimated leaf projection ratio.

Choline and choline metabolites are essential for all cellular functions. They have also been reported to be crucial for neural development. In this work, we studied the functional characteristics of the choline uptake system in human neural stem cells (hNSCs). Additionally, we investigated the effect of extracellular choline uptake inhibition on the cellular activities in hNSCs. We found that the mRNAs and proteins of choline transporter-like protein 1 (CTL1) and CTL2 were expressed at high levels. Immunostaining showed that CTL1 and CTL2 were localized in the cell membrane and partly in the mitochondria, respectively. The uptake of extracellular choline was saturable and performed by a single uptake mechanism, which was Na+-independent and pH-dependent. We conclude that CTL1 is responsible for extracellular choline uptake, and CTL2 may uptake choline in the mitochondria and be involved in DNA methylation via choline oxidation. Extracellular choline uptake inhibition caused intracellular choline deficiency in hNSCs, which suppressed cell proliferation, cell viability, and neurite outgrowth. Our findings contribute to the understanding of the role of choline in neural development as well as the pathogenesis of various neurological diseases caused by choline deficiency or choline uptake impairment.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies has performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations — specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to ATG-G (7.5% vs. 38.3%, p=0.001). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p&lt;0.001), with a shorter time between transplant and CMV (&lt;61 days, 77.8% vs. 33.3%, p=0.008) and a higher median CMV copy number (1000 vs. 0, p=0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p=0.005). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year probability of relapse while comparing ATG-T and ATG-G (32.0% vs 40.3%, p=0.423; 63.9% vs 55.7%, p=0.438, respectively).