Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Developmental, clinical, and epidemiological research have demonstrated the salience of perceived racial discrimination (PRD) as a contributor to negative mental health outcomes in adolescence. This article summarizes secondary analyses of cross-sectional data from a large-scale youth survey within a predominantly rural state to estimate the prevalence and strength of association between PRD and serious psychological distress, suicidal ideation, and prior suicidal attempts. Data from 93,812 students enrolled in Grades 6, 8, 10, and 12 within 129 school districts across Kentucky were examined to determine prevalence rates for subgroups within the cohort. Logistic regression analyses assessed differences and established comparative strength of association among these variables for racial/ethnic subgroups. PRD was self-reported at high rates across several demographic subgroups and was most evident among Black (24.5%) and Asian (22.1%) students. Multiracial students experienced the highest rates of both SPD and suicidality. Both for the entire cohort and for each racial/ethnic subgroup, PRD was significantly associated with increased likelihood of negative mental health outcomes, although the strength of these associations varied across subgroups and developmental levels. Implications for early intervention and prevention are discussed.

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

In order to investigate the size distributions and seasonal variations of carbonaceous aerosols (OC and EC), the carbonaceous species were collected and then analyzed by using a 9-stage Anderson-type aerosol sampler and DRI Model 2001A Thermal/Optical Carbon Analyzer on the typical industrial city Nanjing in Yangtze River Delta, China in the summer, autumn and winter of 2013 and spring of 2014. OC, EC, SOC and POC exhibited obvious seasonal variations, with the highest level in winter (39.1±14.0, 5.7±2.1, 23.6±11.7 and 14.1±5.7 μg•m^-3) and the lowest level in summer (20.6±6.7, 3.3±2.0, 12.2±3.8 and 8.4±4.1 μg•m^-3), and were mainly centralized in PM_1.1 in four seasons. The concentrations of OC in PM_1.1 varied in the order of winter > autumn > spring > summer, while EC ranked in the order of autumn > winter > summer > spring. In the PM_1.1-2.1 and PM_2.1-10, the concentrations of OC and EC decreased in the sequence of winter > spring > autumn > summer. The size spectra of OC, EC and SOC had bimodal distributions in four seasons, except for EC with four peaks in summer. The size spectra of POC varied greatly with seasons, exhibiting bimodal distribution in winter, trimodal distribution in spring and summer, and four peaks in autumn. The OC/EC ratios were 7.0, 6.3, 7.6 and 6.9 in spring, summer, autumn and winter, respectively, which demonstrated the abundance of secondary organic aerosols in Nanjing. The sources of carbonaceous aerosol varied significantly with seasons, and were dominated by vehicle exhaust, coal and biomass burning in PM_2.1, and dominant by dust, coal and biomass burning in PM_2.1-10.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Omega-3 polyunsaturated fatty acids (ɷ-3 PUFAs) offer diverse health benefits, such as supporting cardiovascular health, improving cognitive function, promoting joint and musculoskeletal health, and contributing to healthy aging. Despite their advantages, challenges like oxidation susceptibility, low bioavailability, and potential adverse effects at high doses persist. Nanoparticle encapsulation emerges as a promising avenue to address these limitations while preserving stability, enhanced bioavailability, and controlled release. This comprehensive review explores the therapeutic roles of omega-3 fatty acids, critically appraising their shortcomings and delving into modern encapsulation strategies. Furthermore, it explores the potential advantages of Metal-organic framework nanoparticles (MOF NPs) compared to other commonly utilized nanoparticles in improving the therapeutic effectiveness of omega-3 fatty acids within drug delivery systems (DDS). Additionally, it outlines future research directions to fully exploit the therapeutic benefits of these encapsulated omega-3 formulations for cardiovascular disease treatment.

Whey protein was pretreated with multi-frequency ultrasound in mono, dual, and tri-frequency modes. The effect of multi-frequency ultrasound pretreatment on the hardness, chemical forces, and microstructure of acid-induced whey protein gel was investigated. Whey protein gels pretreated with dual and tri-frequency ultrasound showed higher hardness (p3.35 mm) in those samples were resisted to gastric digestion. Moreover, the tri-frequency ultrasound pretreatment of whey protein gel released the least free amino group during gastric digestion. In contrast, whey protein gel with the mono-frequency ultrasound pretreatment released the highest amount of free amino acid group during intestinal digestion. Findings from this study suggested that gel hardness and network density could modulate the digestion behaviors of protein gels.

Light is a crucial environmental factor that influences the phenotypic development of plants. Despite extensive studies on the physiological, biochemical, and molecular mechanisms of the impact of light on phenotypes, genetic investigations regarding light-induced transgenerational plasticity in Arabidopsis thaliana remain incomplete. In this study, we used Arabidopsis thaliana as the material, then gathered phenotypic data regarding leaf number and plant height under high- and low-light conditions from two generations. In addition to the developed genotype data, a functional mapping model was used to locate a series of significant SNPs. Under low-light conditions, a noticeable adaptive change in the phenotype of leaf number in the second generation suggests the presence of transgenerational genetic effects in Arabidopsis thaliana under environmental stress. Under different lighting treatments, 33 and 13 significant genes associated with transgenerational inheritance were identified, respectively. These genes are largely involved in signal transduction, technical hormone pathways, light responses, and the regulation of organ development. Notably, genes identified under high-light conditions more significantly influence plant development, whereas those identified under low-light conditions focus more on responding to external environmental stimuli.

Molecular hybridization is a widely used strategy in drug discovery and development processes that consists in the combination of two bioactive compounds toward a novel entity. In the current study, two libraries of hybrid derivatives coming from the linkage of sesquiterpene counterparts dihydroartemisinin and artesunic acid with a series of monoterpenes were synthesized and evaluated by cell viability assay on primary and metastatic melanoma cell lines. Almost all the obtained compounds showed micromolar antimelanoma activity and selectivity toward the metastatic form of this cancer. Four hybrid derivatives containing perillyl alcohol, citronellol, and nerol as monoterpene counterpart, emerged as the best compounds of the series, with nerol being active in combination with both sesquiterpenes, dihydroartemisinin and artesunic acid. Preliminary studies on the mechanism of action have shown the dependence of the pharmacological activity of newly synthesized hybrids on the formation of carbon- and oxygen-centered radical species. This study demonstrated the positive modulation of the pharmacodynamic effect of artemisinin semisynthetic derivatives dihydroartemisinin and artesunic acid due to the hybridization with monoterpene counterparts.

To better understand the shape memory materials and self-healing materials, a new series of liquid-crystalline shape memory polyurethane (LC-SMPU) composites, named SMPU-OOBAm, were successfully prepared by incorporating 4-octyldecyloxybenzoic acid (OOBA) into the PEG-based SMPU. The effect of OOBA on the structure, morphology and properties has been carefully investigated. The results demonstrate that SMPU-OOBAm have liquid crystalline properties, triple-shape memory properties and self-healing properties. The incorporated OOBA promotes the crystallizability of both soft and hard segments of SMPU, and the crystallization rate of the hard segment of SMPU decreases when the OOBA-content increases. Additionally, the SMPU-OOBAm forms a two-phase separated structure (SMPU phase and OOBA phase), and it shows two-step modulus changes upon heating. Therefore, the SMPU-OOBAm shows triple-shape memory behavior, and the shape recovery ratio decreases with an increase in the OOBA content. Finally, SMPU-OOBAm shows self-healing properties. The new mechanism can be ascribed to the heating-induced “bleeding” of OOBA in the liquid crystalline state and the subsequent re-crystallization upon cooling. This successful combination of liquid crystalline properties, triple-shape memory properties and self-healing properties make the SMPU-OOBAm composites with many promise applications in smart optical devices, smart electronic devices and smart sensors.

In this study, the olive pomace was considered because of its importance in the environment. So, this study carried out to estimate the total nitrogen content and the fatty acids profile of olive pomace. The olive pomace samples were collected from Irbid, Jarash, Ajloun and Mafraq during the harvesting season 2014 to study the biochemical characteristics of fatty acid composition and the total nitrogen (TN) content. The total nitrogen content was determined by standard Kjeldahl method and the fatty acid profile was detected by gas chromatography (GC). The results show that the total nitrogen content ranged from (0.39 ± 0.0) to (0.62 ± 0.02) with statistically significant difference suggesting that the composition of matrices and their percentage may be responsible for composition of amendments. The calculated total protein percentage ranged between (2.43 ± 0.00) to (3.87 ± 0.17). Also, 13 different fatty acids were quantitatively profiled and quantitated. Oleic acid (C 18:1) was found to be the highest percentage of all other fatty acids and ranged between (59.03%) and (63.81%), moreover the C 18:1/C 18:2 (oil quality) was calculated and C.V% showed variation meaning that nutritional implication could affect the oxidative stability of oils. In conclusion, OP by-product could give a sustainable and alternative-cheap source for fertilizers, pharmaceutical industries, cosmetics and other industries.

Small peptides (SPs), ranging from 5 to 100 amino acids, play integral roles in plants due to their diverse functions. Despite their low abundance and small molecular weight, SPs intricately regulate critical aspects of plant life, including cell division, growth, differentiation, flowering, fruiting, maturation, and stress responses. As vital mediators of intercellular signaling, SPs have garnered significant attention in plant biology research. This comprehensive review delves into SPs' structure, classification, and identification, providing a detailed understanding of their significance. Additionally, we summarize recent findings on the biological functions and signaling pathways of prominent SPs that regulate plant growth and development. The review also offers a forward-looking perspective on future research directions in peptide signaling pathways.

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

This study was designed for the first time to improve phenolic yield and antioxidant activity of ultrasonic-assisted extraction from Acer truncatum leaves (ATL) using response surface methodology, and phenolic composition in ATL extracted under the optimized condition were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol: water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent /100 g d.w. and a maximal DPPH• antioxidant activity of 74241.61 μmol Trolox equivalent/100 g d.w.. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic composition in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloyl-glucoside was interpreted. All these results provided practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

Banana wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is a devastating fungal disease. Biocontrol strategies owned immense potential in inhibiting the spread of Foc TR4. Here, thirty actinobacteria were isolated from soils and screened for their antagonistic activity against Foc TR4. Strain SCA4-21T exhibited broad-spectrum antifungal activity against nine phytopathogenic fungi including Foc TR4. The strain was identified as the genus Streptomyces according to phenotypic characteristics and 16S rRNA gene phylogenetic analysis. Multi-locus sequence analysis based on five house-keeping gene alleles (atpD, gyrB, recA, rpoB, and trpB) revealed that strain SCA4-21T clustered into S. hygroscopicus subsp. hygroscopicus NBRC 13472T with 100% of bootstrap value. Average nucleotide identity and dDDH were 98.49% and 44.30% above the threshold of novel species. Hence, strain SCA 4-21T represented a novel species within the genus Streptomyces, named as Streptomyces luomodiensis sp. nov.. The type strain is SCA4-21T (=GDMCC4.340T= JCM36555T). By the CAZymes analysis, 348 carbohydrate-active enzymes were detected, including 15 chitinases and 8 β-1,3-glucanases. The fermentation broth of strain SCA4-21T showed high activities of chitinase and β-1,3-glucanase, contributing to the antifungal activity. Our results showed an innovative potential biocontrol agent for managing plant fungal diseases, specifically banana fusarium wilt.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Arabinoxylans (AXs) are non-starch polysaccharides with complex structures naturally occurring in grains (i.e., barley, corn, and others) providing many health benefits, especially as prebiotics. AXs can be classified as water-extractable (WEAX) and water-unextractable (WUAX) based on their solubility, with properties influenced by grain sources and extraction methods. A large body of evidence shows that AXs exert an im-portant health impact, including glucose and lipid metabolism regulation and immune system enhancement, which is induced by the interactions between AXs and the gut microbiota. Recent research underscores the dependence of AX physiological effects on structure, advocating for a deeper understanding of struc-ture-activity relationships. While systematic studies on WEAX are prevalent, knowledge gaps persist re-garding WUAX, despite its higher grain abundance. Thus, this review reports recent data on WUAX struc-tural properties (chemical structure, branching, MW) in cereals under different treatments. It discusses WUAX applications in baking and its benefits deriving from gut fermentation.

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important to observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are commonly the collection of substrates such as rocks, plants or pieces of wood in a given body of water and can be cumbersome to examine. Based on preliminary culturing of the polyp stage on glass and plastic microscope slides in the lab, we designed a novel sampling methodology based on submerging 4 substrate types (small glass petri dishes, Hester-Dendy plates, plastic and glass microscope slides) to confirm the presence of C. sowerbii polyps in the field. We tested this method in various lakes in the Illinois-Indiana region (USA). The sampling method we designed was effective in that C. sowerbii polyps (and sometimes colonies) were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows significant potential for improvement; we highlight water flow and competition and predation from other organisms as significant factors influencing the collection of C. sowerbii polyps for future methodologies.

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

In higher education, the cultivation of research competency is pivotal for students’ critical thinking development and their subsequent transition into the professional workforce. While statistics plays a fundamental role in supporting the completion of a research project, it is often perceived as challenging, particularly by students in majors outside mathematics or statistics. The connection between students’ statistical proficiency and their research competency remains unexplored despite its significance. To address this gap, we utilized the supervised machine learning approach to predict students’ research competency, as represented by their performance in a research methods class, with predictors of students’ proficiency in statistical topics. Predictors relating to students’ learning behavior in a statistics course such as assignment completion and academic dishonesty are also included as auxiliary variables. Results indicate that the three primary categories of statistical skills—namely, understanding of statistical concepts, proficiency in selecting appropriate statistical methods, and statistics interpretation skills— can be used to predict students’ research competency, as demonstrated by their final course scores and letter grades. This study advocates for strategic emphasis on the identified influential topics to enhance efficiency in developing students’ research competency. Findings could inform instructors in adopting a strategic approach to teaching the statistical component of research for enhanced efficiency.

A new class of tetrasubstituted imidazole based compounds was synthesized using a multicomponent one-pot synthesis scheme through a cyclo condensation reaction of benzil, aromatic primary amines, aldehydes and ammonium acetate in glacial acetic acid. The synthesized compounds have been analyzed and characterized by melting point, color, conductivity method, CHN analysis, FT-IR, and UV-Visible. The reaction proceeding was examined by TLC after regular intervals of period. To test biological activity, the synthesized compounds have been examined against various bacterial strains. From the analysis of the antibacterial activity of these synthesized compounds demonstrated that all three imidazole compounds have considerable to significant activity against the strains, and compound K2 was found potent comparatively.

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

Mangrove ecosystems are one of the most productive on our planet but have declined globally by 30-50%. Many species rely on mangrove habitat and thus their conversion to aquaculture farms has led to a noticeable loss in commodities such as wild fish stocks. This study aimed to assess 1) the influence of the presence of aquaculture and 2) restoration projects on the ecosystems ability to provide resources. We collected data on mangrove vegetation (i.e., biomass, richness and abundance), soil nutrients (i.e. organic carbon, aluminium and nitrogen), crab abundance and fishing pressure in six sites. We set up 15 plots in each site and collected data between May and July 2023. Via generalised linear mixed models we found that the abundance and richness of crabs was significantly higher in aquaculture plots than in no aquaculture plots. Aquaculture plots had higher topsoil aluminium, topsoil and subsoil Nitrogen, and had lower topsoil Carbon than non-aquaculture sites. Restored sites had less Nitrogen in the topsoil than unmanaged sites. Biomass did not change between aquaculture, restored and unmanaged plots. We found a negative correlation between crab abundance and richness and mangrove DBH, suggesting that the species of crabs present preferred areas with propagules for feeding (e.g., Grapsidae crabs). The content of nitrogen in the subsoil was positively correlated with mangrove richness, diversity and height, suggesting the importance of nitrogen availability for mangrove growth. The content of aluminium in the subsoil was negatively correlated with the content of organic carbon both in topsoil and subsoil, suggesting the detrimental effect of aluminium on the carbon cycle. Fishing practices were observed in all sites during the data collection period. Even if most of the vegetation parameters were not significantly affected by presence of aquaculture or management for restoration, it is clear that important variables such as aluminium carbon, and nitrogen content in the soil and crab assemblages were highly variable.

Protein degradation is a biological phenomena essential for cellular homeostasis and survivor. Selective protein degradation is performed by the ubiquitination system which selectively target proteins that need to be eliminated and lead them to proteasome degradation. In this review, we focus on the ubiquitin-conjugating enzyme E2 O (UBE2O) and highlight the role of UBE2O in many biological and physiological process. We further discuss the UBE2O implications in various human diseases, particularly in leukemias and solid cancers and suggest how UBE2O targeting could be novel strategy in the treatment of different human neoplasia.

The toxic cadmium (Cd) poses a serious threat to plant growth and human health. Populus euphratica CPK21 has previously been shown to attenuate Cd toxicity by reducing Cd accumulation, enhancing antioxidant defense and improving water balance in transgenic Arabidopsis. Here, we confirmed a protein-protein interaction between PeCPK21 and AtNF-YC3 by yeast two-hybrid, HaloTag pull-down and bimolecular fluorescence complementation assays. AtNF-YC3 was induced by Cd and strongly expressed in PeCPK21-overexpressed plants. Overexpression of AtNF-YC3 in Arabidopsis reduced salt inhibition of root length, fresh weight and membrane stability under Cd stress conditions (100 µM, 7 d), suggesting that AtNF-YC3 appears to contribute to the improvement of Cd stress tolerance. AtNF-YC3 improved Cd tolerance by limiting Cd uptake and accumulation, activating antioxidant enzymes, and reducing H2O2 production under Cd stress. We conclude that PeCPK21 interacts with AtNF-YC3 to limit Cd accumulation, enhance the ROS scavenging system, and thereby positively regulate plant adaptation to Cd environments. This study highlights the interaction between PeCPK21 and AtNF-YC3 under Cd stress conditions, which can be utilized to improve Cd tolerance in higher plants.

Soil organic matter (SOM) is important for the global carbon cycle, and hyperspectral remote sensing has proven a promising method for fast SOM content estimation. However, soil physical properties significantly affect the sensitivity of satellite hyperspectral imaging to SOM, leading to poor generalization ability of the estimation model. This study aims to improve the spatiotemporal transferability of the SOM prediction model by alleviating the coupling effect of soil physical properties on the spectra. Based on satellite hyperspectral images and soil physical variables, including soil moisture (SM), soil surface roughness (root mean squared height, RMSH), and soil bulk weight (SBW), a soil spectral correction strategy was established based on the information unmixing method. Two important grain-producing areas in Northeast China were selected as study areas to verify the performance and transferability of the spectral correction model and SOM content prediction model. The results showed that soil spectral corrections based on fourth-order polynomials and the XG-Boost algorithm had excellent accuracy and generalization ability, with residual predictive deviations (RPD) exceeding 1.4 in almost all bands. In addition, when the soil spectral correction strategy was adopted, the accuracy of the SOM prediction model and the generalization ability after model migration were significantly improved. The SOM prediction accuracy based on the XG-Boost corrected spectrum was the highest, with a coefficient of determination (R2) of 0.76, root mean square error (RMSE) of 5.74 g/kg, and RPD of 1.68. The prediction accuracy, R2, RMSE, and RPD of the model after migration were 0.72, 6.71 g/kg, and 1.53, respectively. Compared with the direct migration prediction of the model, adopting the soil spectral correction strategy based on fourth-order polynomials and XG-Boost reduced the RMSE of the SOM prediction results by 57.90% and 60.27%, respectively. The performance comparison highlighted the advantages of considering soil physical properties in regional-scale SOM prediction.

Cotton is the most ubiquitous and profitable fiber with diverse industrial and domestic applications. Grown in over 100 countries, it has a global market value of about $40 billion and employs over 350 million people from fields to textile mills, contributing about 7% of total labor-force recruitment in developing economies. Cotton has an indeterminate growth habit and an extensive tap root system affected by soil physicochemical and environmental conditions. There is a consensus among experts that conventional cotton cultivation still has a long way to attain sustainability, which is essential if cotton will maintain its competitive edge over other natural and synthetic fibers like hemp, polyesters, and rayon. Despite several efforts already committed to growing cotton sustainably, sustainability has eluded cotton cultivation globally because of the intense farm inputs (freshwater, pesticides, and heavy-duty equipment) needs, especially in developing economies. Some of the technological advancements towards achieving the goal of sustainable cotton cultivation include the development of new varieties, improved irrigation and mulching and precision agriculture techniques, application of remote sensing and Unmanned Aerial Systems (UAS) combined with image processing, and the introduction of autonomous and multi-purpose robotic platforms for growing and harvesting cotton. This review attempts to evaluate the successes already achieved by stakeholders in moving cotton towards sustainable production and identify areas where efforts are still needed to reach sustainable production and improved profitability goals for cotton with projections for future research directions.

This research investigates precision enhancement in regional quasi-geoid refinement through ADS80 tri-linear array scanning stereoscopic imagery for aerial triangulation, coupled with GNSS gravity-potential modeling. Acquiring stereoscopic imagery and analyzing triangulation accuracy with the ADS80 camera, we performed this study over the Qinghai-Tibet Plateau's elevated, desolate terrain, collecting 593 GNSS points following high-precision stereoscopic imagery model. Utilizing 12 gravity satellite models, we computed geoid heights and China 1985 Yellow Sea elevations for 28 benchmarks and GNSS points, thereby refining the Qinghai Province Quasi-Geoid Model (QPQM) using geometric techniques. The findings reveal that POS-assisted ADS80 stereoscopic imagery yields high-precision triangulation with maximal horizontal and elevation accuracies of 0.083/0.116 cm and 0.053/0.09 cm, respectively, across five control point arrangements. The RMSE of normal heights for 1985, processed via these GNSS points, achieved decimeter precision. By applying error corrections from benchmarks to the 1985 elevation data from gravity satellites and performing weighted averaging, the precision of EGM2008, SGG-UGM-2, and SGG-UGM-1 models improved to 8.61 cm, 9.09 cm, and 9.38 cm, respectively, surpassing the QPQM by 9.22 cm to 9.99 cm. This research demonstrates that the proposed methods can significantly enhance the precision of regional quasi-geoid surfaces. Additionally, these methods offer a novel approach for rapidly establishing regional quasi-geoid models in the uninhabited areas of the Qinghai-Tibet Plateau.

Natural compounds have diverse structures and are present in different forms of life. Metabolites such as tannins, anthocyanins, and alkaloids, among others, serve as a defense mechanism in live organisms and are undoubtedly compounds of interest for the food, cosmetic and pharmaceutical industries. Plants, bacteria, and insects represent a source of biomolecules with diverse activities, poorly studied in many cases. To use these molecules for different applications, it is essential to know their structure, concentrations, and biological activity potential. In vitro techniques that evaluate the biological activity of the molecules of interest have been developed since the 1950s. Currently, different methodologies have emerged to overcome some of the limitations of these traditional techniques, mainly the reduction of time and costs. However, emerging technologies continue to appear due to the urgent need to expand the analysis capacity of a growing number of reported biomolecules and the lack of therapeutic options to treat various diseases. This review presents an updated summary of the conventional and current methods to evaluate natural compounds' biological activity, including a diagram that summarizes the minimum techniques essential for correctly assessing molecules with biological potential.

Abstract: In network science and big data, the concept of finding meaningful infrastructures in networks has emerged as a method of finding groups of entities with similar properties within very complex systems. The whole concept is generally based on finding subnetworks which have more properties (links) amongst nodes belonging to the same cluster than nodes in other groups (A concept presented by Girvan and Newman, 2002). Today meaningful infrastructure identification is applied in all types of networks from computer networks, to social networks to biological networks. In this article we will look at how meaningful infrastructure identification is applied in biological networks. This concept is important in biological networks as it helps scientist discover patterns in proteins or drugs which helps in solving many medical mysteries. This article will encompass the different algorithms that are used for meaningful infrastructure identification in biological networks. These include Genetic Algorithm, Differential Evolution, Water Cycle Algorithm (WCA), Walktrap Algorithm, Connect Intensity Iteration Algorithm (CIIA), Firefly algorithms and Overlapping Multiple Label Propagation Algorithm. These al-gorithms are compared with using performance measurement parameters such as the Mod-ularity, Normalized Mutual Information, Functional Enrichment, Recall and Precision, Re-dundancy, Purity and Surprise, which we will also discuss here.

Two biotinylated derivatives of the main hop chalcone xanthohumol (1) were prepared by a one-step synthesis via esterification using biotin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) and 4-dimethylaminopyridine (DMAP) as coupling reagents. The products were characterized spectroscopically and their antiproliferative activity toward MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1 and Balb/3T3 cell lines was investigated using the SRB assay. For all three tested compounds the best activity was noted in the case of human (MCF-7) and mice (4T1) breast cancer cell lines (IC₅₀ values < 9 μM). Both biotinylated derivatives showed higher anticancer activity than xanthohumol (1) towards all types of tested breast cancer cells. Double biotinylated xanthohumol (3) proved to be the most active in inhibiting cell growth, with IC₅₀ values equal to 5.35 ± 1.5 μM for 4T1 and 8.03 ± 0.53 µM for MCF-7 cell lines. Compound 3 was also more active than 1 and 2 against liver cancer cells HepG2 (IC₅₀ = 17.37 ± 5.1 μM), while the IC₅₀ values for 1 and 2 were equal to 21.5 ± 2.7 and 22.1 ± 3.9 µM, respectively. 4‑O‑biotinylxanthohumol (2) was the second most active growth inhibitor, particularly with respect to MCF-7 (IC₅₀ = 6.19 ± 1.7 μM) and 4T1 (IC₅₀ = 6.64 ± 0.4 μM) cell lines. The antioxidant activity was evaluated using the 1.1-diphenyl-2-picrylhydrazyl radical (DPPH) method. All tested compounds (1-3) have antioxidant activity between 2.73 and 3.38 mM. It was reported for the first time that new prenylated chalcones containing the biotin moiety effectively inhibited proliferation of cancer cells in vitro.

The G-protein-coupled estrogen receptor (GPER; G protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as potential HGSC ovarian cancer origin (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER antagonist in combination with an agonist on cell viability, providing a better understanding of the effects of these compounds on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

The use of privileged scaffolds as starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that allow to modify the privileged framework chosen and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized by scaffold morphing approach of triazine compounds obtained previously as antiviral agents. Newly synthesized azines were evaluated against lymphoma, hepatocarcinoma, and colon epithelial carcinoma cells showing in five cases acceptable to good anticancer activity associated to low cytotoxicity on healthy fibroblasts. Finally, ADME in vitro studies were conducted on the best derivatives of the two series showing good passive permeability and resistance to metabolic degradation.

Although the influence of climate on the fire regime is unanimously recognized, most publications are studies on this influence are at the global scale. Therefore, this study aims to demonstrate the role of climate in the incidence of wildfires at the country and regional scale using statistical analysis and machine learning methods. Mainland Portugal was chosen as a case study due to its climate and because it is the European region most affected by wildfires. Results demonstrate the climate signature in the spatial and temporal distribution of the wildfire incidence. The conclusions of the study include (i) the existence of two pyro-regions, with different types of climate (Csb and Csa) composed of NUTS II regions: the northern region composed of the Norte and Centro regions and the southern region composed of Alentejo and Algarve; (ii) the intra-annual variability in the incidence of wildfires, characterized by two peaks, one in spring and the other in summer, are a consequence of the country's type of climate; and, (iii) how the annual cycle of wildfire incidence varies over the years depends on the weather conditions throughout each year. These results are of fundamental importance for wildfire managers, especially in the context of climate change.

Fifty-two kinds of N’-phenylhydrazides were successfully designed and synthesized. Their anti-fungal activity in vitro against five strains of C. alb. was evaluated. All prepared compounds owned varying degrees of activity and their MIC80, TAI, and TSI values were calculated. The in-hibitory activities of 27/52 compounds against fluconazole-resistant fungi C. alb. 4395 and C. alb. 5272 were much higher than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. alb. 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the highest inhibitory activity against C. alb. SC5314, 4395, and 5272. The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were higher than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploring the antifungal mechanism revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium mor-phology was damaged. In conclusion, the hydrazide scaffold showed potential in the develop-ment of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and hold potential as novel antifungal agents.

Mercury (Hg) analyses in species of fish are performed for two reasons 1) to safeguard human health, 2) to assess environmental quality, since different environmental changes may increase the Hg concentrations in fish. These analyses are important since both natural and human activities can increase these Hg concentrations, which can vary extensively, depending on the species, age and catching location. Unfortunately, humans consuming Hg contaminated fish or other marine foodstuffs cannot taste Hg contamination; this can be only detected by chemical analysis. If the aim of Hg analysis is to protect the health of marine-food consumers, researchers workers must consider the location where the fish were caught and interpret the results accordingly. Health and environmental officials must appreciate that in specific places many local people may have a daily diet almost entirely consisting of fish or other marine foods, and these individuals should not be exposed to high concentrations of Hg. Regional and national health and environmental officials should follow the guidance of international organizations when drawing their final conclusions about whether or not the products are safe to eat.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

In the context of sustainable and eco-friendly agriculture, current scientific researches are focusing on plant-based bioproducts to remedy the toxicity caused by chemical fertilizers and pesticides. This study was conducted on cladodes of Opuntia ficus-indicato screen the bioactive molecules and to evaluate the activity againstfungal agentsisolated from tomato fruits. Quantitative analysis of the methanolic extractrevealed its richeness in total polyphenols (86.6 mg GAE/100 g FW), flavonoids (13.4 mg QE/100 g FW), condensed tannins (08.9 mg TAE/100 g FW), and carotenoids(0.9 mg β-CE/100 g FW). DPPH test revealed that the cladodes extract had a high antioxidant potential (0.6 mg/ml). On the other hand, 7 fungal agents were isolated from infected tomato fruits and identifyed asbelonging to the following genera: Rhizoctonia (EC2), Fusarium (EC1 and EC3), Alternaria (EC4), Mucor (EC5), Aspergillus (EC6) and Penicillium (EC7). At a concentration 0.02% of cladodehydro-ethanolic extract, results of the antifungal activity showed aninhibition of mycelial growth up to70% for the isolates ofAlternariaspEC4 (70.91%), Rhizoctonia solaniEC2 (58.49%), Fusarium oxysporiumEC3 (57.63%) and Fusarium solaniEC1 (53.13%). While,inhibitory activities lower than 50% were obtained for fungal isolates MucorspEC6 (31.08%), Aspergillus sp EC5 (35.14%) and Penicillium sp EC7 (28.38%).At 0.04%all thecladode hydro-ethanolic extractwere able to inhibit mycelium growth in more than 50%.Similarly, maximum spore inhibition development were obtained with 0.04 cladode hydro-ethanolicreaching more than 60%. Inhibition percentages of 83.02%, 85.96%, 87.76% and 90.20% were obtained for fungal isolates Fusarium oxysporium EC3, Fusarium solani EC1, Rhizoctonia solani EC2 and Alternaria sp EC4, respectively. All together, the results show that Opuntia ficus-indica extract has potential tobe used effectively as a biopesticide against fungal agents of tomato fruits.

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O3-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA inter-ference, and microinjection. The O3-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O3-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O3Pc-MSP gene induced additional O3 mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O3Pc-MSP gene had nine silent mutations compared to the complementary mating type of the E3 homologue gene.

Cigarette smoke (CS) is a major driver of many respiratory diseases including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several bi-ological processes and interfere with several regulatory pathways. The purpose of this study was to assess the effect of active CS on miRNAs expression in AMs obtained from bronchoalveolar lavage (BAL) of ever- or never-smoker subjects and patients with COPD or NSCLC. BAL specimens were collected from 43 sex-matched subjects to determine the expression of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p before and after in vitro CS exposure by RT-PCR. In addition, bioin-formatic analysis of miRNAs target genes linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is noteworthy that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both ever- or never-smokers, 106a-5p in never-smokers and 20a-5p in ever-smokers, shifted towards those found in individuals with COPD, suggesting them like a risk factor in developing this lung condition. Moreover, we identified miRNA targets involved in the immune system or AMs property regulation using in silico analysis. In conclusion, our study iden-tified miRNA signatures in AMs exposed to CS, indicating that CS is an important driver of epige-netic changes that contribute to the onset of various lung diseases.

Pretreatment of cells with proteolysis inhibitors diminished intensity and changed shape of DNICs specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

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

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

The majority of investigations on microbial communities from various environments are presently built on culture-independent methods. Many studies point to the pivotal, selective role of primers targeting hypervariable regions of 16S rRNA in the metabarcoding of bacteria, including cyanobacterial communities. The selectivity of primers designed to amplify targeted regions of the 16S rRNA gene, which has been highlighted by many authors, limited effective amplification. Moreover, the type and specificity of the studied material can also negatively influence the results of 16S metabarcoding. Most of the studies of cyanobacterial communities have been performed for planktonic microbial communities that are often represented by common, well-studied species. In this study, we present the results of 16S metabarcoding analysis using three primer pairs - two already well-known and a third designed in this study - that amplify divergent regions of the 16S rRNA gene (V3-V4, V4-V6, V6) for benthic, microbial mat-forming cyanobacteria communities. Such communities can be a source of toxigenic cyanobacterial taxa and should be monitored with adequate primers. The comparison of three primer pairs suggested that those designed within the present study describe the structure and composition of highly heterogeneous cyanobacterial mats’ communities better than the others

Heavy metals are dangerous contaminants constituting a threat to human health because they persist in soils and are easily transferred into the food chain, causing damages to human health. Among heavy metals, nickel appears to be one of the most dangerous responsible for different disorders. Public health protection requires nickel detection in environment and food chains; a simple, rapid and sensitive method to detect nickel contamination is represented by biosensors. In this paper we report the setup of a whole-cell based system, in which protoplasts, obtained from Nicotiana tabacum leaves, were used as transducers to detect the presence of heavy metal ions and, in particular, nickel ions. Protoplasts were genetically modified with a plasmid containing the GFP reporter gene under the promoter region of a sunflower small HSP gene control. By this device the presence of heavy metal ions was detected. Thus, the possibility to use this whole-cell system as a novel tool to detect the presence of nickel ions in food matrices was assessed.

Plant-derived compounds have been historically used for the treatment of various diseases and an important source of several clinically useful anti-cancer agents. The Artemisia annua is known as a medicinal herb that is effective against cancer. Thus, the purpose of this study was to investigate whether ethanol extracts of Artemisia annua could increase an anti-cancer effect against LS174T cells. Our results show that Artemisia annua extracts (AAE) induces apoptosis through the regulation of mitochondria outer membrane potential. We demonstrate that apoptosis is induced by p53-dependent manner when cells were treated with Nutlin-3 (MDM2 inhibitor) and LY294002 (Akt inhibitor). In addition, the apoptotic effect was also observed in the p53-independent manner through pifithrin-α (p53 inhibitor) and celecoxib (COX-2 inhibitor) treatment. As in in vitro, AAE induced apoptotic effects and regulated apoptosis-related proteins in LS174T xenograft model. Taken together, these results suggest that Artemisia annua extracts exerts an anti-cancer effect through p53-independent manner, as well as p53-dependent manner by p53´ translocation in LS174T colon cancer cells.

Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

Dams fragment stream habitat and fishways around dams typically serve few species that are strong swimmers or jumpers. We test a prototype wetted ramp designed to allow upstream passage of small-bodied fishes while blocking upstream movement of invasive sea lamprey in the Laurentian Great Lakes. We tested short, smooth ramps with 5-10 mm water depth in various combinations of ramp angle, water flow and swim channel width with the aim to selectively block adult migrating sea lamprey while passing sub-adult white suckers (Catostomus commersonii) and creek chubs (Semotilus atromaculatus). Sea lamprey easily passed a 0.75 ramp at 5 angle, but very few individuals passed a similar ramp at 10 angle and none passed a longer ramp at the 5 angle. Limiting the amplitude of tailbeats in a narrow channel did not hamper lamprey or the other species. Greater water flow, and thereby greater immersion depth on the ramp fostered passage for all species. Smaller-bodied individual of creek chubs and white suckers performed best on the ramp. We show that wetted ramps could be incorporated into fishways at low-head dams to aid passage of smaller-bodied fishes while also blocking the spawning migration of adult sea lamprey.

Electrospun ultrathin fibers based on binary compositions of polylactide (PLA) and poly(ε-caprolactone) (PCL) with different ratios of polymer components from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the effect of biopolymers content on the characteristics of the crystal structure of PLA and PCL and the diffusive rotational mobility of the stable TEMPO radical in the amorphous regions of PLA/PCL compositions was shown. It was revealed that after PLA and PCL blending, significant changes in the degree of crystallinity of PLA, PCL segmental mobility, sorption capacity of the radical as well as activation energy of rotational diffusion in the amorphous regions of PLA/PCL composition are observed. The characteristic region of biopolymers’ composition from 50/50 to 30/70 % PLA/PCL blends ratio was found, where the inversion transition of PLA from dispersive medium to dispersive phase where an inversion transition is assumed when the continuous medium of the PLA transforms into a discrete phase. The performed studies made it possible for the first time to carry out a comprehensive analysis of the effect of the system component ratio on the structural and dynamic characteristics of the PLA/PCL film material at the molecular level.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

Two experiments were conducted to develop a Nano green manganese and assess its effect on grapevines. The first experiment was microbiological, where several incorporation strategies were utilized to enrich the yeast with manganese, as follows: (1) adding manganese to the liquid medium (growth phase), (2) adding after 24 h of incubation (non-growth phase). As the results, growth phase reduced the possibility of medium contamination. Manganese concentration in the yeast cells was increased as that of manganese sulphate in the medium. Manganese incorporation in yeast cells was 99.93% higher than that of the medium at 0.0195 g/l of manganese. Although the concentration of manganese in the medium raised the OD of yeast cell biomass, manganese sulphate had no passive influence on it. The second experiment was horticultural, done on Flame Seedless grapevines, since both active fresh and frozen yeast enriched with manganese resulted from the first experiment were sprayed twice a year at 10 or 20 cm3/l comparing with manganese sulphate, and manganese chelate. The results demonstrated that yeast extracts in both forms increased the yield and improved fruit properties. The most effective treatment on vegetative growth, yield and fruit properties was the frozen yeast enriched with manganese at 20 cm3/l.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

Diabetic foot ulcers (DFUs) significantly affect the lives of patients and increase the risk of hospital stay and amputation. We suggest a remote-monitoring platform for better DFU care. This system uses digital health metrics (scaled from 0 to 10, where higher scores indicate a greater risk of slow healing) to provide a comprehensive overview through a visual interface. The platform features smart offloading devices that capture behavioral metrics such as offloading adherence, daily steps, and cadence. Coupled with remotely measurable frailty and phenotypic metrics, it offers an in-depth patient profile. Additional demographic data, wound characteristics, and clinical parameters, such as cognitive function, were integrated, contributing to a comprehensive risk factor profile. We evaluated the feasibility of this platform with 124 DFU patients over 12 weeks; 39% experienced unfavorable outcomes such as dropout, adverse events, or non-healing. Digital biomarkers were benchmarked (0-10), categorized into low, medium, and high risk for unfavorable outcomes, and visually represented using color-coded radar plots. The initial results of case reports illustrate the value of this holistic visualization to pinpoint the underlying risk factors for unfavorable outcomes, including a high number of steps, poor adherence, and cognitive impairment. Although future studies are needed to validate the effectiveness of this visualization in personalizing care and improving wound outcomes, early results in identifying risk factors for unfavorable outcomes are promising.

Newly designed pentacyclic benzimidazole derivatives, featuring amino or amido side chains, were synthesized to assess their in vitro antiproliferative activity. Additionally, we conducted investigations into their direct interaction with nucleic acids, aiming to uncover potential mechanisms of biological action. These compounds were synthesized using conventional organic synthesis methodologies, alongside photochemical and microwave-assisted reactions. Upon synthesis, the newly derived compounds underwent in vitro testing for their antiproliferative effects on various human cancer cell lines. Notably, derivatives 6 and 9 exhibited significant antiproliferative activity within the submicromolar concentration range. Our biological assessment highlighted that the biological activity was strongly influenced by both the position of the N atom on the quinoline moiety and the position and nature of the side chain on the pentacyclic skeleton. Findings from fluorescence, circular dichroism spectroscopy, and thermal melting assays indicated a mixed binding mode—comprising intercalation and the binding of aggregated compounds along the polynucleotide backbone—of these pentacyclic benzimidazoles with DNA and RNA.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

Andean blueberries are wild berries grown and consumed in Ecuador which contain high values of bioactive compounds, mainly anthocyanins, with powerful antioxidant activity. The aim of this study was to evaluate the profile and contents of (poly)phenols and carotenoids in Andean blueberry by HPLC-DAD-MSn and determine a wide range of its biological activities. The antioxidant capacity of this fruit was evaluated in vitro by three different methods and in vivo using the zebrafish animal model, also the toxicity effect was determined by the zebrafish embryogenesis test. Besides, the antimicrobial activity and the capacity of Andean blueberry to produce hemagglutination in blood cells were evaluated. Finally, the bioaccessibility of (poly)phenols and related antioxidant capacity were determined in the different phases of an in vitro digestion. The global results indicated no toxicity of Andean blueberry, weakly bacteriostatic activity, and high contents of anthocyanins and antioxidant capacity, which were partially bioaccesible in vitro (~ 50 % at the final intestinal step), contributing to the knowledge of its health benefits for consumers and its potential use in the food and pharmaceutical industry as functional ingredient.

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl) propanamides were designed and synthesized, combining benzisothiazole and 4-thiazolidinone in one frame. The aim of the study was to verify their effectiveness to contrast the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, advanced glycation products (AGEs), inflammatory cytokines and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level (IC₅₀ = 40 nM).

Food and Agricultural Organisation estimates from 2014 suggest 64% of the high seas migratory stocks are either overfished or undergoing overfishing. Illegal fishing exacerbates the damage to marine ecosystems, human rights, and food security, and is yet to be included in the recent United Nations (UN) draft agreement to protect high seas biodiversity. We used catch data from the Sea Around Us Project to determine trends in fishing gear use and the catches of countries fishing in the high seas. Using Two-way ANOVA, Principal Coordinates Analysis, and SIMPER Test, we found that Spain, Taiwan, Japan, Indonesia, and Ecuador had the highest catches in 2004-2014. Each decade, only 1 in 10 countries (10.8%) caught over 500,000 tonnes, leaving the remaining 90% of countries catching less than 500,000 tonnes. Further analysis showed the mean high seas catch per fishery decreased 55% between the 2000s and the 2010s. Purse seine and longline were increasingly used towards the 2010s. Catch from purse seine and longline accounted for 70.5% and 78.4% of total high seas catch in 1950-2014 and 2004-2014, respectively. Discards were unreported throughout 1950-2014, and the reporting levels of landings varied greatly between countries and gears. We call for immediate action and recommend (1) including international, overarching high seas governance to end illegal and unsustainable fishing in the high seas in the UN draft agreement, and (2) using large mobile marine protected areas in high seas fisheries management through the UN draft agreement.

The mystery phenomenon of fungal bioluminescence has always captivated human curiosity, although more attempts need to be made, particularly to bring the new species to the surface. In this study, we devoted considerable space to the taxonomy of these fungi while discussing their biogeography, evolution, bioluminescence mechanism, and potential ecological roles. We provide a detailed explanation of how these fungi produce light, including the role of the enzyme luciferase and luciferin. We also discussed their applications. Here, we presented an updated list of 122 bioluminescent fungi identified from five distinct evolutionary lineages viz. Armillaria, Eoscyphella, Lucentipes, Mycenoid, and Omphalotus worldwide, mainly in tropical and subtropical areas. The bioluminescent fungi descended from the last common ancestor of the mycenoid and the marasmioid clades of Agaricales, which have been maintained for at least 160 million years of evolution. We highlighted the need for further research to understand the ecological role of bioluminescent fungi. Applying bioluminescent fungi in various areas (e.g., environmental and medicinal) demonstrates their validity.

The promoter of the RECEPTOR-LIKE CYTOPLASMIC KINASE VI_A2 gene contains nine binding sites for the REPLUMLESS transcription factor. In agreement, the expression of the kinase gene was strongly downregulated in the rpl-4 mutant. Comparing phenotypes of loss-of-function mutants, it was revealed that both genes are involved in stem growth, phyllotaxis, organization of the vascular tissues, and the replum, highlighting potential functional interactions. Expression of the RLCKVI_A2 gene from the constitutive 35S promoter could not complement the rpl-4 phenotypes, but exhibited a dominant positive effect on stem growth and affected vascular differentiation and organization. The results also indicated that the number of vascular bundles is independently regulated from stem thickness. Although our study cannot demonstrate the direct link between the RPL and RLVKVI_A2 genes, it highlights the significance of the proper developmental regulation of the RLCKVI_A2 promoter for balanced stem development.

Nicotiana benthamiana plants infected with a potato virus Y isolate (PVYO) under ambient conditions of 25 °C and ~405 parts-per-million (ppm) ambient CO2 display symptoms of chlorosis, leaf curling, and stunting. However, under elevated temperature and CO2 levels (30 °C, 970 ppm), systemic viral titers decrease several-fold, and plants appear asymptomatic. Under the latter conditions we have studied how infection, drought, or both combined affect infection, drought-driven loss of leaf turgor, plant water content, stomatal conductance, metabolome, and hormone (ABA, SA, and JA) levels. We found that drought did not affect viral titers. As expected, drought decreased plant water content and stomatal conductance. Under drought conditions, infection did not alter significantly final water content or loss of leaf turgor progression, but it increased the levels of some sugars and other osmo-protectants. Infection and drought altered the levels of many components of the metabolome. Some components altered by infection were not altered by drought, but most of those altered by drought were also altered by infection. Drought increased the levels of ABA, infection increased the levels of ABA, SA, and JA, and altered their relative balance. The effects of drought and of infection on hormone levels were cumulative when combined. Thus, under ambient conditions that turn a severe infection into an asymptomatic one both, plant physiology parameters and the interplay with drought are affected.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

The tumour-associated isoenzymes, hCA IX and hCA XII catalyze the hydration of carbon dioxide to bicarbonate and protons. These isoforms are highly overexpressed in many types of cancer, where they contribute for the acidification of the tumor environment promoting the tumor cell invasion and metastasis. In this work, in order to identify novel dual hCA IX and XII inhibitors, virtual screening techniques and biological assays were combined. A structure based virtual screening towards hCA IX and XII was performed using a database of approximately 26000 natural compounds. The best shared hits were submitted to a thermodynamic analysis and 3 promising best hits were identified and evaluated in terms of their hCA IX and XII inhibitor activity. In vitro biological assays are in line with the theoretical studies and revealed that Syringin, Lithospermic acid, and (-)- Dehydrodiconiferyl alcohol behave as good hCA IX and hCA XII dual inhibitors.

The transforming growth factor-β (TGF-β), in which overexpression have been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Three series of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–h, 15a–h, 16a–h, 22a, 22b, 22d, 23a, 23b, 23d, 24b, and 24d were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activity in an enzymatic assays. Among these compounds, the most active compound 16f inhibited ALK5 phosphorylation with an IC₅₀ value of 0.28 µM, with 98% inhibition at 10 µM. Compound 16f also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). Molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.

Abnormality of fibroblast growth factor receptors (FGFRs) mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need of new chemotype of FGFR inhibitors, here, we started with a hit structure identified from our internal c-Met inhibitor project, and conducted a chemical optimization. After exploring three parts of the hit compound, we finally discovered a new series of pyrrolo[2,3-b] pyrazine FGFR inhibitors, which contain a novel scaffold and unique molecular shape. We believed that our findings can benefit others to further develop selective FGFR inhibitors.

Resveratrol (RSV), a naturally occurring phytoalexin, is the most important stilbenoid synthesized by plants, as a defense mechanism, in response to microbial aggression, toxins or ultraviolet radiation. RSV came to the attention of researchers both as a potential chemopreventive agent and a possible explanation for the low incidence of cardiovascular disease (CVD) in French people with a high-fat diet. RSV is mainly administered as a food supplement, its properties being evaluated in vitro or in vivo, on various experimental models. RSV modulates signaling pathways that limit the spread of tumor cells, protects nerve cells from damage, is useful in the prevention of diabetes, and generally acts as an anti-aging natural compound. It was highlighted that RSV could ameliorate the consequences of an unhealthy lifestyle caused by an exaggerated caloric intake. This paper reviews the evidence supporting the beneficial effect of RSV for various pathological conditions, e.g., neoplastic diseases, neurodegeneration, metabolic syndrome, diabetes, obesity, CVDs, immune diseases, bacterial, viral, and fungal infections. The study also focused on the chromatographic analysis of trans-RSV (tRSV) in Romanian wine samples, providing a comprehensive overview of tRSV content across different types of wine.

Microplastics (MPs) are a critical environmental issue, with impacts ranging from ecosystem contamination to health risks through bioaccumulation. This review addresses the inefficacy of traditional water treatments in removing MPs and proposes photodegradation, particularly via nanomaterial-enhanced photocatalysts, as a solution. Utilizing their unique properties like large surface area and tunable bandgap, nanomaterials significantly improve degradation efficiency. Different strategies for photocatalysts modification to improve photocatalytic performance are thoroughly summarized, with the particular emphasis on element doping and heterojunction construction. Furthermore, this review thoroughly summarizes the possible fundamental mechanisms driving photodegradation of microplastics facilitated by nanomaterials, with a focus on processes like free radical formation and singlet oxygen oxidation. By clearly elucidating these strategies and mechanisms, this review aims to provide valuable insights and inspire further progress in microplastic photodegradation.

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

The Giant Babax, an endemic bird in China and a nationally protected wildlife species of Class Ⅱ, is primarily distributed in southern and southeastern Tibet. To investigate the factors influencing nesting site selection, this study conducted research on nest characteristics and nesting site preferences at four sample sites around Lhasa from March to October 2023y, using systematic search methods, tracking methods, and sampling methods. The research findings are as follows: (1) The average nest depth was (7.70±1.47)cm, nest height was (19.58±2.97)cm, inner diameter was (10.64±1.73)cm, outer diameter was (24.65±4.8)cm, average weight was (162.3±13.5)g, and average nest spacing within the plot was 396.93m. (2) The nests of Giant Babax were predominantly found on vegetation such as Salix longistamina (38%), Hippophae gyantsensis (20%), Rosa sericea Lindl. (14%), and Populus szechuanica Schneid(11%). They showed a preference for artificial secondary forests as nesting sites. (3) Giant Babax exhibited a preference for habitats with robust trees that had high canopies while being distant from houses and roads, but close to water sources; moreover, the canopy of the nesting tree played a crucial role in their choice of nesting sites. (4) The reproductive success rate reached 76%, with key factors affecting it being the canopy coverage of the nesting tree and the number of helpers. These research results provide fundamental data support for population conservation efforts and ecological resource management strategies concerning the Giant Babax.

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.

Stretch marks are far from being exclusively appearing on pregnant women and appear whenever the body experience a rapid growth. Into the dermis, collagen fibres are altered associated with a loss of orientation and the elastic network is disrupted leading to a fibrotic organisation. This results to epidermal tearing which produce skin lesions. Centella asiatica is a well-known medicinal plants rich in triterpenic actives molecules and traditionally used to treat wounds and help skin repair. The aim of this study was to evaluate Centella asiatica extract as a natural way to solve stretch marks concern and understand its mechanism of action. We have first evaluated the fibroblast’s proliferation based on scratch assay model and their genes expression by RT-qPCR. At the ex vivo level, elastin fibres were quantified by immunofluorescence. Collagen fibre’s orientation and their occupation of the dermis were analysed after Sirius red staining and specific software analysis. We have proven that Centella asiatica has stimulated fibroblasts proliferation, reduced extracellular matrix degradation and fibrosis. On stretch marked skin explant, Centella asiatica increased the occupation of collagen fibres and elastin production. Based on the mechanisms behind the formation of stretch marks, Centella asiatica restores dermis network by optimising fibres organisation for a visible skin remodelling effect.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

One consequence of the global technological advancement in conventional metallurgy is the fast depletion rate of valuable minerals, which are also becoming increasingly difficult to find in pure and economically viable forms. This has spurred more interest in technologies that investigate ability of different microorganisms to mobilize valuable metals from their ores via diverse metabolic processes. This study was carried out therefore to isolate, identify and characterize iron solubilizing bacteria from Iron stones of Agbaja iron ore mining site of Kogi State, Nigeria. Crushed samples in the range of 0.25µm and 0.75µm particle sizes were cultured in a modified 9k media to facilitate bacterial growth and pure cultures were then isolated and sub-cultured for further bioleaching studies. Morphological and biochemical analysis suggests that some of the bacteria identified are members of Acidithiobacillus spp, Pseudomonas spp, and Leptospirillum spp. Studies conducted on pure cultures and mixed consortium of the identified organisms shows that a mixture of the three organisms leached iron ore to about 96.16%. Also results of growth pattern due to bacteria countafter 24-72hours of incubation ranged between 0.1×10³ cfu/ml and 12.3 ×10³ cfu/ml for Acidithiobacillus spp. The need to explore the molecular characteristics of these organisms with a view to generating more information on the quality/quantity of their DNA for future cloning activities was also investigated in this work. DNA was extracted using zymo fungal/bacterial extraction mini prep kit ^TM (cat #6001) and subsequently subjected to 1% agarose gel electrophoresis. Visible bands were obtained with Alpha Innotech Gel Documentation Machine. DNA amplification was carried out using a pettier based thermo cycler PCR machine and electrophoresed on 1.5% agarose gel. Results of the PCR shows a visible band corresponding to 1.5kbp using this primer 27F (5¹-GAGTTTGATCCTGGCTCAG-3¹) and 1492R (5^1-GGTTACCTTGTTACGACT-3¹). DNA purity check shows two of the bacteria possess very good qualities for sequencing for further molecular analysis.

Adult neurogenesis involves generation of functional neurons from neural progenitor cells, which have the potential to complement and restore damaged neurons and neural circuits. Therefore, the development of drugs that stimulate neurogenesis represents a promising strategy in stem cell therapy and neural regeneration, greatly facilitating the reconstruction of neural circuits in cases of neurodegeneration and brain injury. Our study reveals that compound A5, previously designed and synthesized by our team, exhibits remarkable neuritogenic activities, effectively inducing neurogenesis in neural stem/progenitor cells (NSPCs). Subsequently, transcriptome analysis using high-throughput Illumina RNA-seq technology was performed to further elucidate the underlying molecular mechanisms by which compound A5 promotes neurogenesis. Notably, comparative transcriptome analysis showed that the up-regulated genes were mainly associated with neurogenesis and the down-regulated genes were mainly concerned with cell cycle progression. Furthermore, we confirmed that compound A5 significantly affected the expression of transcription factors related to neurogenesis and cell cycle regulatory proteins. Collectively, these findings identify a new compound with neurogenic activity and may provide insights into drug discovery for neural repair and regeneration.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, the polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with the BGCs of spectomycin, julichromes, lincolnenins, and huanglongmycin. Setomimycin BGC includes post-PKS assembly/cycling enzymes StmD (C-9 ketoreductase), StmE (aromatase), and StmF (thioesterase) as key components. The heterodimeric TcmI-like cyclases StmH and StmK are proposed to aid in forming the setomimycin monomer. In addition, StmI (P-450) is predicted to catalyze biaryl coupling of two monomeric setomimycin units, with StmM (ferredoxin) specific to setomimycin BGC. The roles of StmL and StmN, part of the nuclear transport factor 2 (NTF-2)-like protein family and unique to setomimycin BGCs, could particularly interest biochemists and combinatorial biologists. α-Glucosidase, a key enzyme in type 2 diabetes, hydrolyzes carbohydrates into glucose, thereby elevating blood glucose levels. This study aimed to assess the α-glucosidase inhibitory activity of EtOAc extracts of JCM 3382 and setomimycin. The JCM 3382 EtOAc extract and setomimycin exhibited greater potency than the standard inhibitor, acarbose, with IC50 values of 285.14 ± 2.04 μg/mL and 231.26 ± 0.41 μM, respectively. Kinetic analysis revealed that setomimycin acts as a competitive inhibitor of α-glucosidase. Molecular docking demonstrated two hydrogen bonds with maltase-glucoamylase chain A residues Thr205 and Lys480 (binding energy = −6.8 kcal·mol⁻¹), two π-π interactions with Trp406 and Phe450, and one π-cation interaction with Asp542. Residue-energy analysis highlighted Trp406 and Phe450 as key in setomimycin's binding to maltase-glucoamylase. These findings suggest that setomimycin is a promising candidate for further enzymological research and potential antidiabetic therapy.

Peri-implantitis continues to be one of the major reasons for implant failures. We propose a new approach for incorporating MTA into Zirconia implant surfaces with Nd:YAG laser and investigate the biological response of peri-implant cells as well as the microbiological response. Discs of Zirconia stabilized with Yttria and Titanium were produced according 4 tested groups: Nd:YAG laser textured Zirconia coated with MTA (Zr MTA); Nd:YAG laser textured Zirconia (Zr Textured); Zirconia and Titanium discs (Zr and Ti ). Contact profilometry was used to evaluate surface roughness. Human osteoblasts, gingival fibroblasts and S. oralis were cultured on samples. Cell adhesion and morphology, cell viability, cell differentiation markers and bacterial growth were assessed. Zr Textured roughness was significantly higher compared to all other groups. Cellular adhesion was observed at 1 day in all samples in both cell lines. Osteoblasts viability was lower in Zr MTA group, unlike fibroblasts viability was shown to be higher in Zr MTA group compared to Zr Textured group at 3 and 7 days. Osteocalcin and IL-8 release by osteoblasts were higher in Zr MTA. Zr Textured showed higher IL-8 values released by fibroblasts. No differences in S. oralis CFUs were observed between groups. The results suggest that Zirconia implant surfaces coated with MTA seems to promote fibroblasts proliferation and osteoblasts differentiation, however does not appear to have antibacterial properties.

Oral drug absorption is the primary route for drug administration. However, this process hinges on multiple factors, including the drug’s physicochemical properties, formulation characteristics, and gastrointestinal physiology. Given its intricacy and the exorbitant costs associated with experimentation, the trial-and-error method proves prohibitively expensive. Theoretical models have emerged as a cost-effective alternative by assimilating data from diverse experiments and theoretical considerations. These models fall into three categories: data-driven models, encompassing classical pharmacokinetics, quantitative-structure models (QSAR), and machine/deep learning. Mechanism-based models include quasi-equilibrium, steady-state, and physiologically based pharmacokinetics, alongside first principles such as molecular dynamics and continuum models. This review provides an overview of recent modeling endeavors across these categories, evaluating their respective advantages and limitations. Additionally, a primer on partial differential equations and their numerical solutions is included in the supplementary materials, recognizing their utility in modeling physiological systems despite their mathematical complexity limiting their widespread application in this field.

The leather industry is one of the most polluting industries in the world due to the large amounts of waste following the raw hides processing, but also due to the high content of chemicals present in their composition. The main problem of chromium-tanned leather solid waste is related to their storage, because of the ability of chromium to leach in soil or water, and also owing to the high ability of trivalent chromium to oxidize to its toxic form, hexavalent chromium. The purpose of this study is to present the latest methods for extracting trivalent chromium from the composition of solid leather wastes. The extraction methods identified in the present study are based on acid/basic/enzymatic hydrolysis and substitution with the help of organic chelators (organic acids and organic acid salts). In addition, the study includes a comparative analysis between the advantages and disadvantages of each identified extraction method. At the same time, the study also presentes alternative chromium extraction methods based on the combination of conventional extraction methods and ultrasound-assisted extraction.

Biological nitrogen fixation (BNF) by symbiotic bacteria plays a vital role in sustainable agriculture. However, current quantification methods are often expensive and impractical. This study explores the potential of Raman spectroscopy, a non-invasive technique, for rapid assessment of BNF activity in soybeans. Raman spectra were obtained from soybean plants grown with and without rhizobia bacteria to identify spectral signatures associated with BNF. δN15 isotope ratio mass spectrometry (IRMS) was used to determine actual BNF percentages. Partial least squares regression (PLSR) was employed to develop a model for BNF quantification based on Raman spectra. The model explained 80% of the variation in BNF activity. To enhance the model's specificity for BNF detection regardless of nitrogen availability, a subsequent elastic net (Enet) regularization strategy was implemented. This approach provided insights into key wavenumbers and biochemicals associated with BNF in soybeans.

Introduction: In Part I of this three-part series we report a retrospective, population-based cohort study assessing rates of adverse events (AEs) in pregnancy after COVID-19 vaccines compared to the same AEs after influenza vaccines and after all other vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and prevention (CDC) and the U.S. Food and Drug Administration (FDA). The CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024, for adverse events (AEs) involving pregnancy complications following COVID-19 vaccination. The time-period included 412 months for all vaccines except COVID-19 vaccines, having been used for only 40 of the 412 months (December 1, 2020, to April 26, 2024). Proportional reporting ratios (PRR) by time compared AEs after COVID-19 vaccination to those after influenza vaccination, and after all other vaccine products administered to pregnant women. In cases in which the PRR was not applicable, Chi-square analysis and Fisher’s exact tests were used according to CDC/FDA guidance. CDC/FDA stipulate a safety concern if a PRR is ≥ 2 or if a Chi-square is ≥ 4. Results: The CDC/FDA’s safety signals were breached for all 37 AEs following COVID-19 vaccination in pregnancy: miscarriage, fetal chromosomal abnormality, fetal malformation, cervical insufficiency, premature rupture of membranes, premature labor, premature delivery, placental calcification, placental infarction, placental thrombosis, placenta accreta, placental abruption, placental insufficiency, placental disorder, fetal maternal hemorrhage, fetal growth restriction, reduced amniotic fluid volume, preeclampsia, fetal heart rate abnormality, fetal cardiac disorder, fetal vascular mal-perfusion, fetal arrhythmia, fetal distress, fetal biophysical profile abnormal, hemorrhage in pregnancy, fetal cardiac arrest, fetal death (stillbirth), premature infant death, neonatal asphyxia, neonatal dyspnea, neonatal infection, neonatal hemorrhage, insufficient breast milk, neonatal pneumonia, neonatal respiratory distress, neonatal respiratory distress syndrome, and neonatal seizure. All p values were ≤ 0.001 with the majority being <0.000001. Summary statistics for the deviation from the CDC/FDA safety signals mean (n, range) are as follows: PRR 69.3 (46, 5.37 - 499); z statistic 9.64 (46, 3.29 - 27.0); and Chi-square was 74.7 (26, 28.9 - 148). Conclusions: We found unacceptably high breaches in safety signals for 37 AEs after COVID-19 vaccination in pregnant women. An immediate global moratorium on COVID-19 vaccination during pregnancy is warranted. The United States government, medical organizations, hospitals, and pharmaceutical companies have misled and/or deceived the public regarding the safety of COVID-19 vaccination in pregnancy. Promotion of these products must be immediately halted.

Organic fertilizer application in agricultural land is known to improve soil microbial processes, fertility, and yield. In particular, stable changes in soil chemical composition through multi-year fertilization of organic fertilizers are thought to cause changes in the microbial community. Here, the effects of oil cake amendments (OC) on soil bacterial diversity, community profile and enzyme activity were evaluated and compared to those amended with chemical fertilizer (NPK). The comparison of diversity indices between OC and NPK amended soils shows that application of oil cake has increased microbial diversity potentially with an increase in the number of different microbial groups. The ordination plot distinguished and clustered both treatments showing differential effects of soils chemical factors on the microbial communities of each treatment. Proteobacteria, Verrucomicrobia and Bacteriodetes were significantly abundant in OC amended soil than in the NPK received soil, indicating alterations in community structure, composition, and diversity con-current to the changes in pH, Ca and Mg contents of the soil. These shifts in bacterial community structure and composition could also be observed from the phylum to the genus level in both NPK and OC amended soils partially explained by differences in soil chemical factors. The OC soil compared to the NPK amended soil also contain significantly higher abundance of predicted genes corresponding to enzymes related to biogeochemical cycling, decomposition and plant growth promotion. Collectively, these results support the use of an unconventional organic fertilizer positively altering bacterial populations in jujube orchards. The application of oil cake-based organic fertilizer improved microbial diversity and enhanced potential ecosystem functions related to bio-geochemical cycles, mineralization and plant growth promotion.

Predictive studies are essential to establish fundamental data for monitoring and controlling Xylella fastidiosa infections in our country. Limited knowledge exists about how Xylella fastidiosa interacts with the plant host's immune system, leaving numerous unanswered questions regarding Xylella fastidiosa biology and its interactions with national plant hosts. Key inquiries include understanding of how the plant immune system interfaces with Xylella fastidiosa in the xylem and identifying the specific or shared mechanisms underlying the susceptibility of different hosts. Factors such as the presence of insect vectors, abundance of host plants, and climate suitability play pivotal roles in Xylella fastidiosa dispersal. We recommend that countries identified with relatively high risk, like Portugal, undertake thorough individual risk analyses. The implementation of preventive measures and, if necessary, the enhancement of surveillance systems for early detection of Xylella fastidiosa in plants and insect vectors are crucial steps. Additionally, raising awareness is of equal importance to mitigate socioeconomic and ecological impacts on their ecosystems.

Background: The aim of this experimental work was to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants, all the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female and the presence of sex-linked features. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, and can be a valid tool in gender determination but the absence of a database greatly limits its use. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Anxiety is a multifactorial pathology associated with oxidative stress and changes in different neurotransmitters in the central nervous system (CNS). Sarcomphalus joazeiro (Rhamnaceae) has a predicted effect on the CNS, being considered an alternative for pre-clinical investigations of anxiolytic drugs. The objective of this study is to evaluate the chemical composition, analyze the antioxidant capacity and the anxiolytic effect of the ethanolic extract of S. joazeiro leaves (EEFSJ) in zebrafish. The chemical profile was analyzed by liquid chromatography coupled to mass spectrometry (UPLC-PDA-ESI-QDA). Antioxidant action by DPPH• elimination and ABTS•⁺ capture assays. The 96 h acute toxicity and open field and light and dark tests, for sedative and anxiolytic evaluation, respectively, were applied in vivo, using zebrafish. It was possible to identify 11 compounds from the flavonoid and saponin class. EEFSJ exhibited a mean inhibitory concentration (IC50) of 185.2 ± 2.2 µg/mL and 74.17 ± 1.5 µg/mL against the DPPH• and ABTS•⁺ radicals, respectively. In vivo, EEFSJ demonstrated reduced locomotor activity and an anxiolytic effect similar to diazepam via GABAergic systems, without presenting toxicity within 96 h. These results suggest the safety of using EEFSJ for the development of clinical trials for the production of new anxiolytic drugs.

Throughout history, the pursuit of diagnosing and predicting crop yields has evidenced genetics, environment, and management practices' intertwined roles in achieving food security. However, the sensitivity of crop phenotypes and genetic responses to weather and climate remains unclear, hampering the identification of the underlying abilities of plants to adapt to climate change. We hypothesize that the PAWN global sensitivity analysis (GSA) coupled with a genetic by environment (GxE) model -built of environmental covariance and genetic markers structures- can evidence the contributions of climate on the predictability of maize yields in the U.S. and Ontario, Canada (US-CA). The GSA-GxE modeling framework estimates the relative contribution of climate variables such as solar radiation, temperature, rainfall, and relative humidity on improving maize yield predictions in US-CA. We use an improved version of the Genomes to Fields (G2F) initiative multi-dimensional database to build the environmental covariance matrices for the proposed GSA-GxE framework. The PAWN indices show that the aggregated GxE model’s highest sensitivity levels over US-CA were attributed to solar radiation, temperature, rainfall, and relative humidity. In one-third of the locations, rainfall was the primary climate variable responsible for maize yield predictability. Also, a consistent pattern of top sensitivity indices by location indicates that Relative Humidity, Solar Radiation, and Temperature were distributed as the main or the second most relevant drivers of maize yield predictability.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

"Public legal information from all countries and international institutions is part of the common heritage of humanity. Maximizing access to this information promotes justice and the rule of law". In accordance with the aforementioned declaration on Free Access to Law by Legal information institutes of the world, a plethora of legal information is available through the Internet, while the provision of legal information has never before been easier. Given that law is accessed by a much wider group of people, the majority of whom are not legally trained or qualified, diversification techniques, should be employed in the context of legal information retrieval, as to increase user satisfaction. We address diversification of results in legal search by adopting several state of the art methods from the web search, network analysis and text summarization domains. We provide an exhaustive evaluation of the methods, using a standard data set from the Common Law domain that we subjectively annotated with relevance judgments for this purpose. Our results i) reveal that users receive broader insights across the results they get from a legal information retrieval system, ii) demonstrate that web search diversification techniques outperform other approaches (e.g., summarization-based, graph-based methods) in the context of legal diversification and iii) offer balance boundaries between reinforcing relevant documents or sampling the information space around the legal query.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Endophytes are ubiquitous organisms that reside within plant organs and contribute to the growth and well-being of plants. Nevertheless, there is limited knowledge regarding the plant growth-promoting endophytes found in medicinal plants. Therefore, the aims of the present work were to isolate some endophytic bacteria associated with roots, stems, leaves and inflorescences of Aerva javanica, collected from the Shada Alasfal Mountain at Albaha region, Saudi Arabia. After that, they were screened for some of their direct and indirect plant growth-promoting mechanisms. Finally, based upon their internal transcribed spacer 16S rRNA gene sequencing, the isolates were identified. The results showed that the selected endophytes differentially produced IAA and ammonia, and solubilized phosphate as direct mechanisms. In addition, they had exhibited variable capacities to produce some lytic enzymes and HCN beside their antifungal activities. Furthermore, they showed abilities to tolerate some stress conditions. The bacterial endophytes were identified by molecular methods and belonged to the genera of Micrococcus, Enterobacter, Pseudomonas, Delftia and Bacillus. The findings of this study indicated that the bacterial endophytes isolated from Aerva javanica are possessing crucial functions to improve plant growth and could be utilized as biofertilizers or bioagents to establish a sustainable crop production system.

Gold nanoparticles are currently used for the treatment of cancer through a myriad of modalities and delivery approaches. Conjugation of tumor imaging Single Photon Emitting Computed Tomographic (SPECT) radiopharmaceutical to gold nanoparticles will allow systemic targeting and imaging of cancer tissues simultaneously. In this study, gold nanoparticles (AuNPs) were prepared using Epigallocatechingallate (EGCG), loaded with doxorubicin (Dox), and characterized before and after doxorubicin conjugation. Cytotoxicity of EGCG-AuNPs and Dox-EGCG-AuNPs were evaluated against breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) cell lines demonstrating high cytotoxic effects of Dox-EGCG-AuNPs against both cell lines. Doxorubicin was radiolabeled with ^99mTc and our new approach has optimized various labeling conditions resulting in a radiochemical yield of 93.5 ± 2.04%. Biodistribution of ^99mTc-Dox-EGCG-AuNPs was studied in normal and tumor bearing mice following I.V. and intratumoral injections at different time intervals. Results showed high uptake of the intravenously injected ^99mTc-Dox-EGCG-AuNPs in tumor tissue (22.45 %ID/g at 2 h). In addition, localized intratumoral injection of ^99mTc-Dox-EGCG-AuNPs showed extremely high levels of uptake in tumor (80.22 %ID/g at 15 min) with high retention for extended periods post injection. Our results present prospects for the utility of ^99mTc-Dox-EGCG-AuNPs as a multiplexed theranostic agent through SPECT imaging of tumor tissue and therapy through photothermal destruction of cancer tissue through the application of exogenous laser lights as well as through tyrosine phosphatases inhibitor (through EGCG), and topoisomerase II inhibitor (through doxorubicin) effects.

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

Fusarium species are agriculturally important fungi with a broad host range and can be found as endophytic, pathogenic, or opportunistic parasites in many crop plants. This study aimed to identify Fusarium species in bare-rooted, dormant plants in Turkish grapevine nurseries using molecular identification methods and assess their pathogenicity. Asymptomatic dormant plants were sampled from grapevine nurseries (43) in different regions of the country, and fungi were isolated from plant roots and internal basal tissues. The Fusarium isolates were identified by performing gene sequencing (TEF1-α, RPB2) and phylogenetic analyses. Pathogenicity tests were carried out by inoculating mycelial agar pieces of isolates onto the stem or conidial suspensions into the rhizosphere of vines (1103 Paulsen rootstock). Laboratory tests revealed that Fusarium species were highly prevalent in Turkish grapevine nurseries (41 out of 43). Gene sequencing and phylogenetic analyses unraveled that 12 Fusarium species (F. annulatum, F. brachygibbosum, F. clavum, F. curvatum, F. falciforme, F. fredkrugeri, F. glycines, F. nanum, F. nematophilum, F. nirenbergiae, F. solani, and Fusarium spp.) existed in the ready-to-sale plants. Some of these species (F. annulatum, F. curvatum and F. nirenbergiae) consistently caused wood necrosis of seedling stems, rotting of the basal zone and roots, and reduced root biomass. Although the other nine species also caused some root rot and root reduction, their virulence was not as severe as the pathogenic ones, and they were considered opportunistic parasites or endophytic species. This study is the first detailed investigation of Fusarium species in grapevine nurseries in Türkiye and emphasizes the need to consider pathogenic species in producing healthy grapevine seedlings.

The unique structure of G4.0 PAMAM dendrimers allows the drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin (DOX) were optimized. The physicochemical properties of the system were monitored using DLS, CD, and fluorescence spectroscopy. The QCM-D method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the ITC isotherm. Fluorescence spectra and release curves identified reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of G4.0-DOX was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is important from a therapeutic point of view.

Citrus species essential oils (EOs) are significant sources of bioactive compounds and demonstrate diverse therapeutic effects. However, limited documentation exists regarding the phytochemicals associated with their biological activities. This study aims to assess the antioxidant activity, plant inhibitory properties, and brine shrimp cytotoxic effects of EOs derived from three Citrus species: C. sinensis, C. limon, and C. hystrix. Utilizing chemometric analysis and gas chromatography-mass spectrometry (GC-MS) fingerprints, the volatile components contributing to antioxidant activity were elucidated. The peels of the Citrus samples were hydro-distillated to obtain EOs, and subsequently subjected to antioxidant, plant inhibitory, and brine shrimp cytotoxic assays. The results indicated that C. limon EO exhibited the highest antioxidant activity, while C. hystrix and C. sinensis EOs demonstrated pronounced inhibitory effects against Aetrmia salina and Lactuca sativa, respectively. GC-MS analysis facilitated the identification of key compounds in each EO. Principal component analysis (PCA) and hierarchy cluster analysis (HCA) effectively categorized Citrus EOs based on their antioxidant properties, highlighting the proximity of C. limon and C. sinensis. Among the identified compounds, D-limonene, α-Terpineol, Caryophyllene, (+)-3-Carene, β-Pinene, (-)-Spathulenol, trans-p-Mentha-1(7),8-dien-2-ol, and trans-Verbenol were the most discriminating compounds affected the antioxidant activity of C.limon and C. sinensis EOs.