Search Results (19,423)

Ten substituted quinobenzothiazinium salts were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All the compounds inhibited AChE in the IC₅₀ range of 0.03–0.658 µM, with 5,8,10-trimethyl-12H-quinolino[3,4-b][¹,⁴]benzothiazin-5-ium chloride (3d) being the most potent inhibitor, with an IC₅₀ value significantly better than that of the clinically used rivastigmine and galantamine and comparable to that of tacrine and donepezil. The IC₅₀ values for BChE inhibition ranged from 0.34 to 4.25 µM; 5,9-dimethyl-12H-quinolino[3,4-b][¹,⁴]benzothiazin-5-ium chloride (3b) exhibited the strongest BChE inhibitory activity and in general, all the investigated compounds were more potent inhibitors than rivastigmine and galantamine. Based on the calculated selectivity index values, they are rather preferential inhibitors of AChE. Cytotoxicity tests performed on normal human dermal fibroblasts (HFF-1) did not demonstrate any significant cytotoxicity under the tested conditions. The distance-oriented structure distribution for the studied molecules was related with the activity data using principal component analysis and hierarchical clustering analysis. (SAR)-based evaluation is reported to predict activity cliffs using a similarity–activity landscape index for the AChE inhibitory response values. Moreover, direct protein-mediated in silico methods were utilized to identify factors that may be relevant for quantitative (Q)SAR modeling. In practice, target-oriented molecular docking was used to organize the spatial distribution of the ligand property space for the anti-AChE system. In general, this series of alkylated quinobenzothiazinium salts with potent inhibitory activity against cholinesterases fulfills Lipinski’s rule of five based on in silico predictions and is also expected to have high absorption in the human gastrointestinal tract. All active derivatives are also expected to penetrate the blood–brain barrier, making them promising compounds for further research and possible use in Alzheimer’s disease therapy. Full article

Vegetation carbon stock is a key component of the terrestrial carbon cycle and supports climate-change mitigation and carbon-neutrality strategies. While field inventories provide accurate references, they are constrained by cost and limited scalability, motivating the rapid adoption of remote sensing for large-scale spatial estimation and mapping. However, the literature lacks a consolidated bibliometric and critical synthesis focused on above-ground vegetation carbon stock estimation. Therefore, this review aims to provide a quantitative overview of publication trends, synthesise methodological developments, and identify key research gaps in remote-sensing-based above-ground vegetation carbon stock estimation. A total of 1825 Web of Science records (2015–2024) were retrieved, of which 763 were included for bibliometric mapping using VOSviewer version 1.6.20 and CiteSpace version 6.3.R2, complemented by a critical review of 32 high-quality studies. Results indicate a shift from passive optical and single-index approaches toward active sensing and multi-sensor, multi-platform integration, alongside broad uptake of machine learning and an emerging dominance of deep learning for nonlinear modelling and feature learning. Research attention is expanding beyond forests to non-forest ecosystems, yet challenges persist in spatial resolution, validation data availability, and cross-biome generalizability. This review summarizes methodological trajectories and identifies priorities for robust, transferable above-ground carbon estimation. Full article

Radon is a significant indoor air pollutant and a leading cause of lung cancer in non-smokers. While geogenic radon potential is well-documented, the specific contribution of building materials—particularly historic stones and those containing industrial by-products—requires precise in situ characterization to ensure public safety. This study investigates radon activity concentrations and surface exhalation rates across three distinct case studies in Slovakia: a mid-20th-century structure with cinder blocks, a UNESCO-protected Gothic building featuring volcanic andesite, and a historic stone plinth. Continuous radon monitoring and accumulation chamber measurements were employed, integrated with the tracking of meteorological parameters. The results revealed the highest surface exhalation rate in cinder block masonry (8.98 Bq m⁻² h⁻¹), followed by andesite ashlars (7.9 Bq m⁻² h⁻¹) and stone (1.87 Bq m⁻² h⁻¹). A clear correlation was observed between indoor radon levels and barometric pressure, whereas the influence of outdoor temperature appeared negligible. An estimated Activity Concentration Index of 0.30 suggests that the volcanic rock is likely radiologically safe for use as a bulk building material. The study concludes that while specific materials contribute to exhalation, indoor radon stability is primarily governed by barometric variations and the effectiveness of floor barriers against geogenic ingress rather than the masonry itself. Full article

This study examines how regulatory heterogeneity in digital services trade relates to the carbon intensity of bilateral trade flows. Using a structural gravity framework estimated with Poisson pseudo maximum likelihood (PPML), we analyzed 10,719 bilateral observations from the Eora Multi-Region Input–Output (MRIO) database over 2014–2020. Bilateral gaps in the OECD Digital Services Trade Restrictiveness Index (DSTRI) were used as the main measure of regulatory heterogeneity, and the overall gap was decomposed into infrastructure-related hard barriers and institutional soft barriers. The results suggest that digital regulatory gaps are associated with a higher carbon intensity in trade while also being associated with lower total embodied emissions through reduced trade volumes. This indicates that lower aggregate emissions under regulatory divergence may reflect contraction in trade activity rather than genuine environmental improvement. The decomposition analysis further suggests that infrastructure-related misalignment is more closely associated with carbon inefficiency, whereas institutional divergence operates mainly through its association with trade volume. In addition, environmental policy stringency in the importing country appears to strengthen the positive association between institutional regulatory gaps and carbon intensity, consistent with the possibility of regulatory overload. The study contributes to the sustainability literature by showing that carbon intensity provides a more informative indicator of sustainable trade performance than aggregate emissions alone in fragmented regulatory environments. It also suggests that digital governance, trade policy, and environmental policy should be considered together in promoting more sustainable forms of international trade, particularly in the context of emerging policy frameworks such as WTO digital trade negotiations, OECD digital governance initiatives, and carbon border adjustment mechanisms (CBAMs). Full article

Invasive plant species are increasingly recognized not only as ecological threats but also as potential sources of bioactive compounds with agricultural applications. However, the combined allelopathic and insecticidal potential of Ailanthus altissima’s different plant parts remains insufficiently explored. This study evaluated the bioactivity of different plant part (leaf, bark, and branch) extracts of A. altissima. Secondary metabolites were characterized by HPLC–DAD–MS, while ethanol extracts (0.5–5%) were tested on wheat (Triticum aestivum) seed germination, seedling growth, oxidative status, and on the survival and repellency of the rice weevil (Sitophilus oryzae). Biological responses were strongly plant part and concentration-dependent. Leaf extracts contained the highest phenolic levels, dominated by caffeoylquinic acids and quercetin derivatives, whereas bark and branch extracts showed lower but compositionally distinct profiles. Despite this, bark and branch extracts produced the strongest biological effects, inhibiting germination energy and root growth at higher concentrations, while leaf extracts stimulated seedling performance, including increased vigor index, while in insect bioassays, bark and branch extracts caused higher mortality and stronger suppression of rice weevil populations. This study provides new evidence that biomass extracts of the invasive species A. altissima represent a promising source of biologically active compounds with both allelopathic and insecticidal properties, highlighting its potential valorization as a plant-based biopesticide for sustainable pest management. Full article

Background: Respiratory syncytial virus (RSV) is a leading global pathogen of acute lower respiratory tract infection, posing significant risks to infants, the elderly, and immunocompromised patients. Artemisia argyi Levl.et Vant Extract (AALE) and its active components have a variety of pharmacological effects, but their anti-RSV potential remains unclear. The aim of this study is to investigate the anti-RSV activity of AALE and parthenolide and its underlying mechanisms. Methods: Cell counting kit-8 (CCK-8) assay was used to determine the anti-RSV activities of AALE and parthenolide. Time-of-addition assay and phase of action analysis were used to explore the effect of drugs on the viral replication cycle. Quantitative polymerase chain reaction (qRCR), immunofluorescence (IF) and Western blot (WB) were used to investigate the effects of AALE and parthenolide on RSV-F gene and protein and on RIG-I/TLR-3 pathway related molecules in vitro. In vivo antiviral efficacy was verified by hematoxylin–eosin (HE) staining for lung histopathology, quantitative real-time PCR (qPCR) quantification of RSV-F, RIG-I, TLR-3, IRF3, IL-6, and IFN-β gene expression in lung tissues, and enzyme-linked immunosorbent assay (ELISA) for serum IL-6 and IFN-β levels. Results: AALE exhibited the strongest anti-RSV activity among the extracts (SI = 27.6), while parthenolide was the most potent monomeric compound (SI = 8.19). In vitro, both AALE and parthenolide were effective in the co-treatment and post-treatment models, reducing RSV-F gene and F protein levels in infected cells. Furthermore, they alleviated RSV infection by regulating RIG-I and TLR-3 pathway-related genes and proteins. In vivo, AALE and parthenolide suppressed lung index and RSV proliferation, attenuated lung injury, and down-regulated RIG-I, TLR-3, IRF3, IL-6, and IFN-β expression in the lungs of RSV-infected mice. Conclusions: AALE and its component parthenolide can inhibit the invasion and replication of RSV, making it a potential candidate for the treatment of RSV-related diseases. Full article

Concurrent with the rising consumption of ultra-processed, high-calorie diets and the decline in physical activity, obesity and related cardiovascular conditions among young adults have continued to increase, becoming an important global public health concern. This study integrates non-invasive Internet of Things (IoT) sensing devices, including the TERUMO ES-P2000 blood pressure monitor (Terumo Corp., Tokyo, Japan) and the PhysioFlow PF07 Enduro cardiac hemodynamic analyzer (Manatec Biomedical, Poissy, France), with an artificial neural network (ANN) for cardiac index (CI) prediction. Through appropriate data preprocessing and model training strategies, the generalization ability and stability of the proposed CI prediction model were significantly enhanced. Experimental results demonstrate that, when using three physiological parameters as input, the ANN achieved a classification accuracy of 97.78%, substantially outperforming traditional approaches. Even under two-parameter input conditions, the model maintained strong predictive performance. These findings confirm the effectiveness and practical potential of the proposed framework for real-time, non-invasive CI assessment. Moreover, this research has received rigorous assessment and approval from the Institutional Review Board (IRB) under application number 202501987B0. Full article

Particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) are two operationally defined fractions frequently used in studies related to soil organic carbon (SOC) dynamics. However, the changes and governing mechanisms of these fractions, particularly along a restoration chronosequence, remain poorly understood. Here, we investigated changes in SOC fractions, soil properties, and microbial communities across a restoration chronosequence (1, 5, 7, 13, and 20 years) of alpine meadows using a space-for-time substitution approach on the Qinghai–Tibet Plateau. We quantified the contributions of biotic and abiotic drivers using Spearman correlation analysis, linear regression and random forest analysis. The results revealed a unimodal pattern in SOC, POC, and MAOC contents, peaking at 7, 5, and 7 years, respectively, with no further increase thereafter. Restoration duration strongly shaped microbial community structure and observed species richness, but had no significant effect on Shannon index and Pielou index. Random forest analysis identified soil water content (SWC) and total nitrogen (TN) as the primary predictors of SOC. The microbial community composition dominated the variation in POC while enzyme activity was the key driver of MAOC. Our findings highlight that soil carbon accumulation during alpine meadow restoration is a nonlinear process with a temporal threshold, and POC and MAOC are regulated by distinct biotic and abiotic mechanisms. This study provides a theoretical basis for understanding carbon sequestration mechanisms during alpine meadow restoration and developing sustainable grassland management strategies. Full article

Exercise adaptation depends on overload that is resolved by recovery, yet the same biology becomes maladaptive when immune, endocrine, metabolic, and muscle-centered stress signals fail to normalize. Exercise-induced maladaptation represents a systems-level failure of biological resolution, with direct relevance to disease-like dysregulation. Functional overreaching, non-functional overreaching, and overtraining syndrome remain difficult to diagnose because no single biomarker provides adequate specificity, temporal stability, or clinical portability. This narrative review synthesizes human and mechanistic evidence across proteomics, transcriptomics, metabolomics, endocrine profiling, extracellular vesicles, and mitochondrial quality-control biology to define the molecular architecture most relevant to athlete monitoring. Across these layers, the most coherent signatures cluster in immune-acute-phase activation, redox-buffering strain, endocrine drift, altered substrate availability, excitation–contraction dysfunction, integrated stress-response signaling, and defects in autophagy–mitophagy and lysosomal remodeling. Three translational elements emerge from this synthesis: a systems-convergence model of recovery failure, a staged biomarker deployment hierarchy, and a provisional recovery failure index. The practical priority is therefore not a solitary marker, but serial phenotype-anchored multimarker panels that connect circulating signals with muscle-centered biology and support decision-making before prolonged recovery failure becomes entrenched. Full article

Background/Objectives: To evaluate construct (convergent and divergent) validity and conduct confirmatory factor analysis (CFA) of the National Center on Health, Physical Activity and Disability (NCHPAD) Wellness Assessment (NWA) tool. Methods: A cross-sectional survey validation study utilizing secondary data. We assessed Spearman correlations between NWA and 36-Item Short Form Health Survey (SF-36), NWA and Godin Leisure-Time Exercise Questionnaire (GLTEQ) and NWA and Modified Fatigue Impact Scale (MFIS) scores to determine construct validity. A CFA was conducted to test the appropriateness of a three-factor model for NWA. Results: Data from 149 participants were used to assess construct validity and from 180 participants for CFA. Both correlations between NWA mental wellness domain and SF-36 mental component scores and between NWA emotional/spiritual wellness domain and SF-36 emotional well-being scores were 0.61 (p < 0.001 for both). The correlation between NWA physical wellness domain and SF-36 physical component score was −0.06 (p = 0.45). The correlations of NWA with GLTEQ overall and with health contribution scores were 0.26 and 0.30, respectively (p < 0.001 for both). The correlations of all NWA domain and MFIS subscale scores ranged between −0.42 and −0.25 (p < 0.05). The CFA model’s comparative fit index was 0.90. Conclusions: The NWA physical wellness domain did not demonstrate strong convergent validity, as mental and emotional/spiritual wellness domains did. All domains showed strong divergent validity, and CFA showed evidence supporting a three-factor model. Future efforts will emphasize refining and reevaluating the physical wellness domain until it achieves strong psychometric properties. Full article

Background/Objectives: Cancer patients increasingly present to emergency departments, posing unique clinical and organizational challenges. Data on this population in Poland remain limited. Methods: A retrospective study was conducted in two hospitals in northern Poland (January–March 2023). All adult patients with active cancer presenting to the ED were included (n = 552, 3.1% of visits). Data included demographics, cancer type, presenting complaints, Emergency Severity Index (ESI), disposition, and in-hospital mortality. Multivariable logistic regression models were used to assess predictors of hospitalization, hospice referral, and mortality, reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: Mean age was 68 years; 51% were female. The most common cancers were lung, breast, colorectal, and prostate. Leading complaints included abdominal pain (15%), trauma (7.5%), and dyspnea (7%). Most patients were triaged as ESI 3–4 (87%). Hospitalization rate was 58%, hospice referral 6%, and in-hospital mortality 7.1%. Lower ESI levels were significantly associated with hospitalization (OR 0.57; 95% CI 0.44–0.73), hospice referral (OR 0.40; 95% CI 0.25–0.63), and in-hospital mortality (OR 0.29; 95% CI 0.18–0.47). Conclusions: Oncology patients represent a small but high-risk ED population. While ESI reflects acute severity, it may not adequately capture palliative care needs. These findings suggest opportunities to improve integration of palliative care in ED settings. Full article

This study aims to provide insights into how physical activity is associated with sleep patterns in youth populations, in particular, Slovak adolescents, and how gender (boys vs. girls) and age (≤16 vs. ≥18) moderate this relationship, using an extreme-group comparison approach that excludes 17-year-olds to enhance contrast between developmental stages. Using a cross-sectional design, self-reported data were collected from 2504 (100%) high school students (aged 15–19; 45.6% boys, 54.4% girls) using the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and the Pittsburgh Sleep Quality Index (PSQI). Participants aged 17 years were excluded from age-stratified analysis to create clearer separation between early/mid and late adolescence. The primary outcome was global sleep quality (PSQI > 5). Secondary outcomes included sleep duration and PSQI component scores. All other analyses (age- and gender-stratified comparisons and interaction models) were predefined as exploratory and hypothesis-generating to examine potential effect modification. Age-stratified analyses among girls showed that, within the low PA group, good sleep was reported by 37.7% of younger girls (≤16) and 28.6% of older girls (≥18). Among older girls, the proportion reporting good sleep increased to 49.8% in the high PA group (χ² = 29.16, p < 0.001). No consistent associations between PA and sleep quality were observed among boys; however, significant association was identified among younger boys (≤16 years), which was not observed in older boys. Logistic regression revealed a modest interaction between age and PA level in predicting sleep quality among girls (β = 0.346, p = 0.049), suggesting small age-dependent variation in the association. This effect should be interpreted cautiously given its borderline statistical significance. Component-level PSQI analyses showed that girls experienced higher rates of sleep disturbances (χ² = 91.40, p < 0.001), longer sleep latency (χ² = 26.71, p < 0.001), and greater daytime dysfunction (χ² = 79.90, p < 0.001). These findings provide region-specific evidence from Central and Eastern Europe and underscore the need for age- and gender-sensitive public health strategies targeting both physical activity promotion and better sleep outcomes, given their observed associations. Full article

The use of colored LED lights is a tool for controlling the development of lymphoid organs and the immune system in general. This study aims to analyze the effects of using simple and combined colored LED lights throughout a 6 week period (1–42 days of age). In this study, 336 one-day-old chicks were used, separated randomly into four groups with different sex and lighting systems, with each group being divided into four separate replicates (4 × 21 birds). The chicks in the WL-Male and WL-Female were exposed to white LED light (WL, 400–760 nm) for 6 weeks, while the chicks in the G-GxB-BL-Male and G-GxB-BL-Female were exposed to a combination of monochromatic lights as follows: green (560 nm) from 1 to 14 days of age, green and blue (480–560 nm) for 15–28 days of age, and blue lights (480 nm) for 29–42 days of age. The use of a mixture of green and blue LED lights (G-GxB-BL) resulted in a significant decrease in the average daily feed intake and feed conversion ratio compared to white light, without causing changes in the body weight of the chicks, average daily gain, mortality rate, and coefficient of variability. G-GxB-BL lights also improved the morphological development of the bursa of Fabricius (BF) compared to white light by significantly increasing the organ index and the lymphoid follicle area. At the same time, G-GxB-BL light compared to white light improved B lymphocytes proliferation in the BF by significantly increasing the lymphocyte density in lymphoid follicles, as well as the number of PCNA-positive cells. This light treatment had these results due to the activation of melatonin receptors, which led to a significant increase in Mel1a-positive cells and a significant decrease in the number of RORα-positive cells. These results demonstrate that G-GxB-BL lights improved the growth performance and immune response in the BF of broiler chickens. Full article

Oxidative stress occurs when there is an excess of reactive oxygen species (ROS) in the cell, primarily produced by mitochondria. Excess ROS trigger membrane lipid peroxidation (LPO), cause mitochondrial swelling, and release proapoptotic proteins into the cytoplasm, which can lead to apoptosis. It is assumed that antioxidants that reduce excessive ROS formation by mitochondria can increase the body’s resistance to stress factors. We investigated the effects of hypoxia and the antioxidant Ambiol (2-methyl-4-dimethylaminomethylbenzimidazole-5-ol dihydrochloride) on the functional characteristics of mitochondria, which were assessed by measuring lipid peroxidation intensity using spectrofluorimetry, mitochondrial membranes fatty acid composition using chromatography, mitochondrial morphology using atomic force microscopy, and respiration rate using polarography. Injecting mice with Ambiol at a dose of 10⁻⁶ mol/kg for 5 days prevented the stress-induced activation of lipid peroxidation, a decrease in the unsaturation index of C₁₈ and C₂₀ fatty acids in mitochondrial membranes, and swelling of these organelles. The drug also increased the efficiency of oxidative phosphorylation during the oxidation of NAD-dependent substrates. Furthermore, Ambiol increased the lifespan of mice by 3.0–4.0 times under various types of hypoxia. Ambiol’s ability to maintain initial (control) levels of C₁₈ and C₂₀ unsaturated fatty acids appears to protect against stress-induced mitochondrial dysfunction. Full article

Baicalin, a natural plant-derived compound, holds promise in addressing clinical bacterial resistance when combined with antibiotics. This study evaluated the antibacterial activity of the combination of baicalin and cefotaxime and explored its mechanism of action on the cell wall and biofilm of multidrug-resistant Pseudomonas aeruginosa (MRPA). The results showed that the combination of baicalin and cefotaxime exerted a synergistic inhibitory effect on the growth of MRPA, with a fractional inhibitory concentration index (FICI) of 0.28. Mechanistically, compared with cefotaxime alone, the combination of baicalin and cefotaxime enhanced the permeability of the cell membrane and cell wall of MRPA, thereby increasing cell damage. It also exhibited stronger antibiofilm activity by inhibiting numerous virulence factors (pyocyanin, elastase, lectin), reducing cellular metabolic activity, and downregulating the expression of biofilm genes (pslA, pelA, algD) and quorum-sensing genes (lasl, lasR, rhll, rhlR, pqsA, pqsR). The molecular docking results revealed that baicalin could stably bind to wbpE, LasR, and RhlR. Therefore, this interaction may indirectly influence the processes related to antibiotic resistance and biofilm formation in bacterial cells. Metabolomic analysis revealed that the combination of baicalin and cefotaxime upregulated 863 metabolites and downregulated 587 metabolites. These metabolites mainly included amino acids, lipids, nucleotides, carbohydrates, and secondary metabolites. The combination primarily enriched key pathways such as amino acid metabolism, lipid metabolism (sphingolipid metabolism) and secondary metabolite biosynthesis. Through these pathways, it triggers significant metabolic reprogramming, thereby interfering with the supply of cell wall synthesis precursors, membrane structural stability, and the generation of biomembrane matrix. Ultimately, it synergistically enhances the effects of cell wall damage and biomembrane inhibition. In conclusion, this study confirms that the combination of baicalin and cefotaxime exerts significant synergistic antibacterial activity against MRPA. It also reveals the mechanism of action of the combination on the cell wall and biofilm of MRPA at the metabolic level, providing theoretical support for the development of novel strategies to combat MRPA. Full article