Search Results (21,627)

Background: Aralia echinocaulis has therapeutic effects on rheumatoid arthritis (RA), with total polysaccharide and glycoside (TPGs) as main active components. RA pathogenesis involves gut microbiota dysbiosis and immune‒metabolic crosstalk, but the role of microbiota-derived succinate in RA remains unclear. Objective: This study explored the role of succinate-GPR91 signaling in intestinal dendritic cells (DCs) in the context of RA and the therapeutic mechanism of A. echinocaulis TPGs. Methods: Collagen-induced arthritis (CIA) mice were treated with TPGs or exogenous succinate. Paw edema, inflammation, gut succinate levels, the Th17/regulatory T (Treg) balance, and DC activation via succinate-GPR91 were detected, and GPR91-targeting siRNA and CD4+ T-cell coculture assays for verification. Results: TPGs alleviated symptoms in CIA mice and restored the Th17/Treg balance by reducing intestinal succinate levels. Succinate activated DCs via GPR91 to promote Th17 differentiation, while TPGs suppressed DC maturation and Th17-driven inflammation, supporting the involvement of a gut-centric immunometabolic axis in RA. Conclusion: TPGs ameliorate RA by targeting the succinate-GPR91-Th17 pathway, identifying succinate as a novel RA target and TPGs as a potential microbiota-modulating agent. Full article

Background: Veterinarians are pivotal to wildlife health surveillance and game-meat safety, yet these topics receive limited emphasis in many veterinary curricula. Understanding students’ perceptions can inform targeted educational improvements. Methods: We conducted a cross-sectional, anonymous online survey among students enrolled in the Integrated Master’s in Veterinary Medicine at ICBAS-UP (Portugal). The questionnaire covered sociodemographic, meat and game-meat consumption, perceived appeal of working with game animals, and multi-select views on hunting, game-meat consumption and the veterinary role. We computed descriptive statistics and tested associations between categorical variables using Pearson’s Chi-square or Fisher’s exact tests (Monte Carlo correction when appropriate). Results: Of the 391 eligible students, 152 responded (39%). The majority (76%) associated hunting with veterinary inspection of game meat and research in epidemiology and emerging diseases, and many (72%) recognized as core roles monitoring the health of game animals and the contribution to public health and environmental sustainability. Significant associations included: prior game-meat consumption with finding game animals appealing/interest in learning more; year of enrolment with recognising hunting as an economic activity and acknowledging veterinary inspection and public health contributions; and perceiving game animals as appealing with associating hunting with population control (all p < 0.05; Cramer’s V indicating weak–moderate effects). Conclusions: Students show awareness of veterinary roles in game-animal health and meat inspection, but interest in working with game animals is low and knowledge gaps persist (e.g., inspection of game meat). Findings support curricular integration of wildlife health, game-meat inspection and One Health. Multicenter studies and evaluation of educational interventions are warranted. Full article

Climate change and rapid urbanization are intensifying urban pluvial flooding and threatening sustainable urban development. This study proposes a three-stage, four-dimensional framework (TSFD-UPFR) to assess urban pluvial flood resilience across resistance, response, and recovery phases that integrate natural, infrastructural, social, and economic dimensions. Using a representative urban catchment affected by a typical extreme rainfall event, we couple hydrological–hydrodynamic simulations with multi-source remote sensing and socio-economic indicators at a 100 m grid resolution to enable spatially explicit assessment. The results indicate moderate overall resilience with pronounced spatial heterogeneity. Resistance is primarily constrained by drainage capacity and impervious surfaces, response is shaped by road connectivity and public service accessibility, and recovery is determined by essential facility restoration and economic support. Low-resilience clusters are concentrated in dense built-up areas and transport hubs, revealing structural weaknesses in adaptive capacity. By linking flood processes with socio-economic recovery dynamics, the framework captures cross-stage interactions within urban systems. The findings support climate-adaptive planning, targeted infrastructure investment, and resilience-oriented governance, contributing to sustainable and equitable urban transformation in megacities facing intensifying extreme rainfall. Full article

Wildfire occurrence in temperate Europe is increasingly shaped by the interaction of human activities and short-term climatic anomalies rather than by natural ignition processes alone. This study analyses national wildfire statistics from Slovakia covering the period 2010–2025 to investigate temporal trends in wildfire occurrence, ignition causes, and fire-related impacts, including economic damages and human casualties. Official fire records provided by the Fire Research Institute of the Ministry of the Interior of the Slovak Republic were analyzed using descriptive and exploratory statistical methods. The dataset includes annual information on wildfire frequency, detailed ignition cause classifications, direct economic losses, fatalities, and injuries. European-scale wildfire patterns were considered for contextual comparison using data from the European Forest Fire Information System (EFFIS). Results show that wildfire occurrence in Slovakia is overwhelmingly dominated by human-caused ignitions, with negligence-related activities forming a persistent baseline of ignition pressure throughout the study period. The extreme wildfire year 2012, during which more than 11,000 wildfire events were recorded, illustrates how routine human behaviors can be strongly amplified under climatically favorable conditions without altering the underlying cause structure. Importantly, wildfire impacts were found to be weakly correlated with fire frequency, as years with moderate numbers of fires occasionally generated disproportionately high economic damages and casualties. These findings demonstrate that wildfire risk in Slovakia is primarily driven by behavioral ignition patterns modulated by short-term climatic variability. The results support a shift towards prevention-oriented and impact-focused wildfire risk management strategies, consistent with current European policies emphasizing integrated risk assessment, early warning, and targeted prevention in temperate regions. Full article

International timber trade has accelerated the global spread of the invasive red-haired pine bark beetle H. ligniperda, posing persistent challenges to phytosanitary inspection and border biosecurity. Rapid isothermal amplification assays are increasingly deployed in frontline quarantine settings to support timely regulatory decisions. However, their performance under the heterogeneous biological backgrounds typical of traded timber remains insufficiently evaluated, particularly with respect to the practical implications of low-level false-positive signals. We re-evaluated a previously reported isothermal assay for H. ligniperda using conditions that simulate timber transport and routine customs workflows. Fifty non-target arthropod species (predominantly insects), selected from quarantine interception records, were included to represent taxa likely to co-occur in operational contexts. Material from Lema decempunctata consistently generated weak but reproducible amplification signals across replicates. Sanger sequencing excluded contamination, confirming low-level non-target amplification in complex biological matrices. Although the signals were faint, ambiguous results in quarantine settings may trigger shipment detention, confirmatory laboratory testing, or temporary trade restrictions, thereby increasing inspection workload, delaying clearance, and generating avoidable compliance costs. These findings indicate that trade-mediated species assemblages can compromise assay performance beyond expectations derived from conventional taxonomy-based specificity testing. To reduce interpretive uncertainty and associated regulatory burden, we propose a tiered diagnostic workflow combining rapid on-site isothermal screening with specificity-oriented SYBR Green qPCR confirmation. This strategy enhances diagnostic reliability while preserving operational efficiency in applied biosecurity surveillance. Full article

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and one of the few solid tumors with a steadily rising incidence, paralleling global trends in obesity and insulin resistance. Its strong epidemiologic association with systemic metabolic dysfunction positions EC as a uniquely accessible model for metabolically informed chemoprevention. Methods: This narrative review was conducted through a systematic search of PubMed/MEDLINE and Embase using the following terms: “endometrial cancer” AND (“insulin resistance” OR “metabolic syndrome” OR “PI3K” OR “chemoprevention” OR “bariatric surgery” OR “metformin” OR “cellular senescence”). Searches were limited to English-language publications; no date restriction was applied for foundational molecular studies, while clinical and translational evidence was reviewed from 2000 to 2025. Additional references were identified through manual review of reference lists of included articles. Results: We examine metabolic amplification as a conceptual framework in which hyperinsulinemia, inflammatory reinforcement, and redox-epigenetic modulation intensify proliferative signaling in biologically susceptible endometrial tissue, particularly within molecular subtypes enriched for PI3K pathway activation such as tumors lacking a specific molecular profile (NSMP). Bariatric surgery offers the strongest human evidence supporting the principle that durable metabolic correction can substantially reduce EC incidence. In contrast, pharmacologic interventions including metformin, anti-inflammatory agents, and nutraceutical compounds demonstrate variable or limited preventive efficacy, and short-term biomarker modulation cannot substitute for validated reduction in cancer risk. The endometrial intraepithelial neoplasia (EIN) model provides a uniquely accessible platform for biomarker-guided intervention. Conclusions: Integration of genomic subtype classification with metabolic profiling may enable precision prevention strategies in clearly defined high-risk populations. Effective chemoprevention will require molecular enrichment, confirmation of tissue-level target engagement, and clinically meaningful endpoints, while acknowledging the translational limits of pathway-directed approaches. Full article

The use of biostimulants in agriculture is increasing; however, their effects on raspberry remain insufficiently understood. The aim of this study was to evaluate the impact of foliar-applied biostimulants on yield and growth in three primocane raspberry cultivars grown under field conditions using multispectral imaging based on unmanned aerial vehicles. An experiment included a control and four foliar biostimulant treatments based on animal-derived amino acids, plant-derived amino acids, seaweed extract, and seaweed extract combined with animal-derived amino acids. Biostimulant effects on primocane raspberry were found to vary substantially depending on cultivar, environmental conditions, and formulation type, with measurable impacts on both yield formation and vegetative growth. These responses were further supported and characterized using multispectral UAV-based mutlispectral imaging, which enabled effective detection of treatment-related physiological changes. This approach was based on the analysis of relative percentage changes between consecutive measurements of selected vegetation indices, allowing the identification of dynamic physiological responses over time. These findings highlight the need for a more targeted approach to biostimulant use, taking into account cultivar-specific responses and environmental variability. Future research should extend this framework to a broader range of genotypes, cultivation systems, and biostimulant formulations, while integrating remote sensing with other analytical methods to better understand plant physiological responses. Such developments may support the transition toward data-driven and precision-guided biostimulant application strategies in sustainable crop production. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder for which there are limited pharmacotherapies. Sodium rutin (NaR), a soluble flavonoid derivative, has shown beneficial metabolic effects, but its role in NAFLD remains unclear. This study investigates whether NaR ameliorates high-fat diet (HFD)-induced NAFLD and insulin resistance through promoting hepatic lipophagy. Methods: Male mice aged 8 weeks old were fed a HFD for 12 weeks with/without NaR supplementation. Body weight was measured every week. After 12 weeks of treatment, GTT and ITT were performed to assess insulin resistance. Then, the tissues were collected and hepatic histology, serum biochemistry, and markers of autophagy and senescence were assessed. Results: NaR treatment significantly attenuated HFD-induced weight gain, reduced visceral fat and liver weights, and ameliorated hepatic steatosis and vacuolization. NaR improved serum lipid profiles; lowered alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels; and reduced hepatic cellular senescence. NaR enhanced hepatic autophagy, evidenced by decreased p62 levels, increased LC3-II/LC3-I ratio, and enhanced colocalization of lipid droplets with LC3 and LAMP1 in vivo and in vitro. These changes were accompanied by improved glucose tolerance and insulin sensitivity. Conclusions: NaR effectively alleviates HFD-induced NAFLD and insulin resistance by activating hepatic lipophagy. These findings support NaR as a promising multi-targeted therapeutic candidate for NAFLD. Full article

Background: Aging is the strongest risk factor for prostate cancer (PCa). It is accompanied by progressive epigenomic divergence, known as epigenetic drift, particularly affecting DNA methylation at regulatory regions. However, the extent to which age-associated promoter methylation contributes to coordinated microRNA (miRNA) expression changes in PCa remains incompletely characterized. Methods: We conducted an integrative in silico analysis of 449 primary tumors from the TCGA-PRAD cohort. Age was modeled as a continuous variable. Age-related miRNA expression changes were estimated from miRNA-seq data using DESeq2. Promoter DNA methylation changes (±2 kb from transcription start sites) were assessed using Illumina 450K arrays and linear regression. MiRNAs showing significant age-associated alterations at both expression and methylation levels were classified as concordant or discordant based on directionality and prioritized using an effect size-based concordance score. We analyzed experimentally validated targets of prioritized miRNAs through functional enrichment and network-based approaches to identify convergent regulatory pathways. Results: Initially, we identified 105 age-associated miRNAs. After filtering, 65 candidates remained. Of these, we found 37 miRNAs with significant age-associated changes at both layers, including 20 concordant and 17 discordant miRNAs. These comprised well-characterized cancer-associated miRNAs and lesser-studied candidates enriched in CpG-rich regulatory regions. Network analyses revealed a limited set of genes under convergent regulation by multiple age-associated miRNAs. These implicated pathways are related to cell cycle control, apoptosis, stress response, and epigenetic regulation. Conclusions: Our findings support a model in which age-dependent promoter methylation drift contributes to coordinated miRNA deregulation in PCa. This convergence highlights biologically plausible miRNA biomarkers and age-sensitive epigenetic circuits relevant to prostate carcinogenesis. Full article

Background/Objectives: Prevention of virus-related cancers is a multifaceted process shaped by vaccination and public awareness. This study assessed awareness of virus–cancer relationships and willingness to vaccinate against a cancer-associated virus among medical and non-medical students. We also evaluated whether human papillomavirus (HPV)-vaccinated students demonstrate greater awareness of the HPV-cancer link compared to unvaccinated students, and examined willingness to vaccinate against a certain cancer-associated virus according to HPV vaccination status. Methods: This cross-sectional survey was conducted in Poland (October 2023–June 2024) and included 1013 first- and second-year university students recruited via convenience sampling. Participation was voluntary and anonymous. Results: Awareness of virus–cancer relationships was low, ranging from 19% for Epstein–Barr virus-related cancers to 43.8% for HPV-related cervical cancer. Women were more likely than men to recognize the HPV–cervical cancer link (OR = 2.08, p < 0.001), supporting gender differences and the need for gender-neutral HPV education with targeted strategies for men. Medical students demonstrated higher awareness than non-medical students. HPV vaccination coverage was low (14.5%), with higher uptake among medical students (21.2% vs. 8.2%). Notably, 41.3% of non-medical students and 7.5% of medical students had never heard of HPV vaccination. Willingness to vaccinate against a cancer-associated virus varied according to perceived infection risk. Conclusions: These findings highlight the need for targeted educational interventions to improve awareness of HPV–cancer links and risk perception, as well as to ensure ongoing education of both HPV-vaccinated and unvaccinated individuals to support informed health decisions and vaccine acceptance. Full article

Lanyin Mandarin is a major regional variety of Mandarin Chinese with phonological characteristics that interact with the acquisition of the codified Standard Mandarin norm. This study examined the pronunciation of Standard Mandarin by 67 native speakers from the Lanyin Mandarin area using a large-scale subjective listening experiment (12 listeners, 6700 tokens), with deviations analyzed across initial consonants, finals, and tones. Based on the perceptual results, a pronunciation deviation database was established (N = 20,100 monosyllabic tokens), enabling targeted acoustic comparisons with Standard Mandarin. The results reveal several systematic patterns with quantified deviation rates. For initial consonants, the highest deviation rates were observed for /l/→/n/ (30.5%), /s/→/ts/ (25.5%), and /ts^h/→/ts/ (20.2%), significantly exceeding their reverse substitutions (/n/→/l/: 13.3%, /ts/→/s/: 0.0%, /ts/→/ts^h/: 15.4%; all p < 0.001). For finals, /iŋ/→/in/ showed the strongest asymmetry (61.2% vs. 21.9% for the reverse), followed by /əŋ/→/ən/ (40.2%) and /ən/→/əŋ/ (39.2%). Tonal deviations were dominated by Tone 3 identified as Tone 2 (31.7%), with Tone 1→Tone 2 at a lower rate (8.4%). These deviations exhibited significant directional asymmetries (e.g., /l/→/n/ vs. /n/→/l/: χ²(1) = 768.06, p < 0.001). Acoustic analyses indicated that consonant confusions corresponded to F2/F3 formant convergence (e.g., Lanyin-biased /l/ F2 values approached Standard Mandarin /n/), while nasal finals showed F2 fronting (higher F2 values approaching Standard Mandarin /in/). Tonal analyses revealed a compressed pitch range (2.4 semitones narrower than Standard Mandarin), with flattened Tone 3 contours contributing to Tone 2 confusion. Together, these findings demonstrate quantifiable, systematic, and directional phonetic patterns in the acquisition of Standard Mandarin by Lanyin dialect speakers, supported by converging perceptual and acoustic evidence. Full article

Previous studies on velvet antler processing have mainly evaluated single techniques, and systematic comparisons of processing combinations are limited. This study investigated the effects of different processing combinations on the nutritional composition and physicochemical properties of velvet antler from red deer and sika deer. A 2 × 2 factorial design was applied: Blood-Retained vs. Blood-Removed and Boiled/Fried (zhuzha; no deep-frying) vs. Vacuum Freeze-Dried. In this study, Boiled/Fried was treated as a single processing method. The four processing combinations were analyzed as independent groups using one-way ANOVA. Additionally, two-way ANOVA was conducted to evaluate the main effects of pretreatment, dehydration method, and their interaction on the measured indices. To account for species background, a three-way ANOVA (species × pretreatment × dehydration) was further conducted for key indices. Moisture, crude protein, ash, and crude fat contents were determined. All composition-related indices were evaluated on both wet-weight and dry-weight bases to distinguish moisture-driven concentration or dilution effects from processing-related retention changes. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted for multivariate evaluation. Spearman’s rank correlation was used for association analysis, and Pearson’s correlation with linear regression was applied to quantify linear relationships (reported as r). Freeze-drying significantly reduced moisture content (p < 0.01) and increased crude protein content (p < 0.05). PCA and OPLS-DA demonstrated clear compositional separation among the four processing combinations, with moisture and crude protein as the main contributors (cumulative explained variance > 83%). The effects of Blood-Retained and Blood-Removed treatments differed between species. Three-way ANOVA indicated significant species-dependent effects (e.g., species × pretreatment and or species × dehydration interactions), while the pretreatment × dehydration interaction was significant for TAAs. In the Boiled/Fried groups, total amino acid content (TAA) decreased with increasing moisture. In the Freeze-Dried groups, moisture was significantly negatively correlated with TAAs in the Blood-Retained treatment (Pearson r = −0.886, p < 0.05), whereas no significant correlation was observed in the Blood-Removed treatment (r = 0.429, p > 0.05). Wet- versus dry-basis comparisons indicated that some between-treatment differences were attributable to moisture-related concentration or dilution effects, whereas differences persisting on a dry basis more directly reflected processing-related nutrient retention. Processing combinations produced species-dependent effects in velvet antler. The three-way ANOVA supported species-dependent pretreatment effects and confirmed that the influence of blood retention or removal on amino acid outcomes was contingent on the dehydration regime (pretreatment × dehydration for TAAs). From an application standpoint, no single processing route is universally optimal across all quality attributes; freeze-drying provides a robust baseline, whereas the choice of blood retention or removal should be made in a target-oriented manner (e.g., physicochemical stability versus protein and amino acid retention) while accounting for species background and interaction effects. Therefore, these findings provide a scientific basis for improving product quality, processing efficiency, and standardization in China’s velvet antler industry. Full article

Universities play a critical role in knowledge creation and technological innovation, serving as key drivers of regional development. However, existing research has paid limited attention to the mechanisms through which university innovation inputs translate into firm-level performance, particularly in the context of science and technology corridors in emerging economies. This study investigates how university innovation resources affect enterprise performance in the G60 Science and Technology Corridor within China’s Yangtze River Delta, one of the country’s most dynamic innovation regions. Using a panel dataset of 55 universities across nine cities from 2008 to 2017, we employ spatial analysis and fixed-effects panel regression models to examine the relationship between university innovation inputs and firm performance and further explore the mediating roles of local human capital and firm R&D investment. The results show that university innovation inputs significantly enhance enterprise performance, although excessive human resource inputs exhibit a negative effect on both short-term and long-term outcomes. Local human capital and firm R&D investment serve as key mediating mechanisms, with input and output resources influencing enterprise performance through distinct pathways. Heterogeneity analysis reveals that non-state-owned enterprises and small- and medium-sized enterprises derive greater long-term benefits from university resources. These findings contribute to the literature by clarifying the conceptual distinction between university innovation inputs and outputs, and by demonstrating the micro-level mechanisms—R&D investment and human capital—through which university-generated knowledge affects firm performance. The results also provide empirical evidence from an emerging economic context, extending the applicability of knowledge spillover and absorptive capacity theories. Policy implications include optimizing university human resource allocation, strengthening university–enterprise collaboration, and providing targeted support for non-state-owned enterprises and SMEs. Future research may extend the analysis to include institutional factors and university heterogeneity. Full article

Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase, a key acyltransferase in the phenylpropanoid pathway and a canonical member of the BAHD acyltransferase family (BAHD), catalyzes the formation of pivotal intermediates in the biosynthesis of secondary metabolites such as lignin, chlorogenic acid, and flavonoids. These compounds serve indispensable protective functions in terrestrial plants, underpinning their adaptive responses to abiotic stresses such as drought, ultraviolet (UV) radiation, and oxidative damage. Although the role of HCT/HQT in the core phenylpropanoid pathway has been extensively characterized, its precise functional contributions to the flavonoid biosynthetic branch—particularly with respect to substrate selectivity, kinetic regulation, and metabolic channeling—remain incompletely understood. This review systematically analyzes the structural features, spatial conformation, catalytic mechanism, and substrate promiscuity of HCT/HQT to clarify its molecular determinants of activity and specificity. Furthermore, it highlights regulatory factors influencing HCT/HQT gene expression, such as transcription factors (MYB, bHLH, WRKY), phytohormones (GA₃, Eth, MeJA, 6-BA, MT), and abiotic/biotic stressors (temperature, blue light, nitric oxide, nano-selenium). Collectively, these insights illuminate how plants dynamically fine-tune phenylpropanoid metabolism in coordination with developmental programs and environmental challenges. This work provides a foundation for further research on HCT/HQT and supports efforts to develop improved crop varieties through targeted regulation of this central metabolic node. Full article

Background/Objectives: In recent years there has been a consistent development of clinical studies surrounding the incorporation of the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) into the treatment of acute myeloid leukemia (AML) Methods: A search of the literature showed a tremendous development of experimental and clinical studies evaluating the impact of VEN-based regimens in the treatment of AML patients. This review comprehensively analyzes the available scientific evidence—including prospective clinical trials, retrospective cohorts, and real-world studies—to summarize current knowledge on the efficacy and safety of venetoclax-based regimens in AML patients. Results: Recent studies have evaluated VEN-based regimens in newly diagnosed (ND) and refractory/relapsed (R/R) AML patients, showing the efficacy of these treatments. VEN with hypomethylating agents (HMAs) became the standard-of-care for elderly/unfit AML patients. Recent studies strongly support the effectiveness of VEN-based regimens in frontline treatment of adult AML patients eligible for intensive treatments. VEN-based therapies were also used in combination with targeted therapies, thus generating triplet therapeutic regimens that are under evaluation for the treatment of some AML subtypes. However, the response to VEN+HMAs is highly variable and in part depends on tumor genetics; some patients are resistant or relapse following VEN-based treatments and future studies will be required to develop therapeutic strategies able to circumvent resistance and to identify patients at high risk of relapse. Prospective randomized trials are required to establish the real efficacy of VEN in various clinical settings and to refine maintenance and discontinuation strategies, aiming to improve long-term outcomes and to make more safe treatments based on VEN. Full article