Search Results (14,469)

Background: Bile salt hydrolase (BSH) is a key probiotic trait, as it facilitates both host metabolism and bacterial survival into the gastrointestinal tract (GIT), through bile acid (BA) deconjugation, keeping intestinal homeostasis. Objectives: The present study aims to investigate the viability of the Lacticaseibacillus rhamnosus VB4 strain and its effects on bile acid deconjugation during the gastrointestinal tract (GIT) passage, under a fed condition, using the in vitro SHIME^® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: Gastric, small intestinal and colonic fractions were monitored and a fecal slurry from a healthy donor was inoculated into the colonic compartment to establish the intestinal microbiota. Samples were collected at the end of stomach, duodenum, jejunum, ileum phases, and colon after 0, 16 and 24 h. Strain survival was assessed by culturing method, and bsh gene expression was revealed by quantitative PCR (qPCR). In addition, UHPLC/HR-MS was performed to reveal the hypothetical changes in BAs profile after strain administration. Results: Good survivability of the VB4 strain in the upper GIT was revealed. Furthermore, VB4-inculated sample showed sustained expression of bsh in both the stomach/small intestine and colon fractions at all sampling times. Analysis of the BAs profile shown that the VB4 strain reduced the levels of the main conjugated BAs in the small intestine under fed condition and improved the deconjugation efficiency during colonic transit compared with the control. Conclusions: These findings highlight the survivability of L. rhamnosus VB4 strain inside the gut and its potential as biotherapeutic BAs-mediator candidate, demonstrating that transcriptomic and metabolomic approaches coupled to a dynamic in vitro gut model represent a robust tool for selection of a BSH-positive probiotic candidate. Full article

Background: Spexin is a neuropeptide involved in various physiological functions, including energy metabolism, appetite regulation, and weight loss. This study aimed to identify correlations between circulating spexin levels, obesity, and insulin resistance (IR) in Korean children and adolescents. Methods: We included 128 Korean children and adolescents in the study. Among them, 69 individuals (53.9%) were classified as obese, 43 (33.6%) were considered overweight, and 16 (12.5%) had a normal weight. We recorded participants’ anthropometric parameters, fasting biochemical parameters, and homeostasis model assessment for insulin resistance (HOMA-IR), and assessed their correlations with plasma spexin levels. Results: Plasma spexin levels were significantly lower in obese subjects than in controls (mean, 163.1 vs. 198.4 pg/mL; p = 0.01). Subjects with IR had lower spexin levels than those without IR (mean, 145.3 vs. 185.1 pg/mL; p < 0.001). Spexin levels were negatively correlated with the BMI SDS (r = −0.30; p < 0.001), systolic blood pressure (r = −0.33; p < 0.001), fasting insulin (r = −0.41; p < 0.001), HOMA-IR value (r = −0.41; p < 0.001), triglyceride (TG) level (r = −0.38; p < 0.001), and plasma leptin level (r = −0.26; p = 0.004). In multivariate analysis, HOMA-IR and TG levels were independently associated with plasma spexin levels (p < 0.001 for both). Mediation analyses suggest a potential bidirectional relationship between obesity-related reductions in circulating spexin and insulin resistance. Conclusions: Decreased circulating spexin levels were associated with obesity and IR among Korean children and adolescents. Our findings suggest a link between circulating spexin, obesity, and IR in this population. Full article

The dynamic behavior and biologically mediated transformation of microplastics (MPs) in crustaceans remain insufficiently explored in aquatic ecotoxicology. In this study, we employed the red swamp crayfish (Procambarus clarkii) as a model organism to systematically investigate the accumulation, distribution, fragmentation, and excretion kinetics of MPs within its digestive system under controlled conditions. We exposed crayfish to fluorescent polystyrene microplastics (50 μm) at a high concentration (100,000 particles/L), which exceeded typical environmental levels but was necessary to track accumulation and fragmentation dynamics within the experimental timeframe, and dissections were performed at 24, 48, and 96 h. Spatiotemporal patterns and morphological changes in MPs were analyzed using advanced microscopic imaging techniques. The results revealed a peak in MP accumulation at 48 h, followed by a decrease at 96 h, suggesting a dynamic equilibrium between ingestion and elimination. Over time, particle sizes decreased significantly, a result consistent with microplastic fragmentation. Additionally, feed supplementation during depuration was associated with increased fragmentation efficiency. Morphological analysis showed digestion-induced changes such as surface wrinkling, irregular edges, and particle shrinkage. These findings elucidate the transformation mechanisms of microplastics within crustaceans and provide crucial insights for assessing their potential ecological risks and fate as pollutants. Based on results from high-concentration short-term laboratory exposure studies, this paper further indicates the necessity for in-depth exploration into the long-term dynamics of microplastics within aquatic organisms and the potential for their transfer across trophic levels. Full article

Anecdotal reports have recently circulated suggesting that intramuscular injection of bacteriostatic saline (BS)—which contains benzyl alcohol (BnOH)—can reverse botulinum toxin type A (BoNTA)-induced brow ptosis. Given the well-established intracellular persistence of BoNTA’s light chain and its irreversible cleavage of SNAP-25, such rapid functional recovery challenges existing pharmacological understanding. This study employed high-resolution pharmacokinetic/pharmacodynamic (PK/PD) modelling using the AesthetiSim™ platform to systematically evaluate this hypothesis. A total of 30,000 virtual patients were randomized to receive BoNTA alone, BoNTA followed by BS injection, or BoNTA followed by normal saline (NS) at Day 7. The model incorporated BoNTA diffusion, internalization, SNAP-25 cleavage, neuromuscular output, and transient BS effects on membrane permeability and endosomal trafficking. Simulated recovery trajectories were tracked over 90 days. The primary outcome, time to 80% restoration of baseline frontalis muscle force (T₈₀), averaged 42.0 days in the BoNTA-only group and 35.5 days in the BS group (Δ = −6.5 days; p < 0.001). Only 13.9% of BS-treated patients reached the T₈₀ threshold by Day 30. Partial reactivation (T₃₀) occurred earlier with BS (21.8 ± 5.3 days vs. 27.3 ± 4.9 days), and the area under the effect curve (AUEC) was increased by 9.7%, reflecting higher overall muscle function over time. In molecular simulations, BnOH produced a minor rightward shift in the BoNTA–SNAP-25 dissociation curve, but receptor occupancy remained above 90% at therapeutic toxin concentrations, suggesting no meaningful impairment of binding affinity. A global Sobol sensitivity analysis demonstrated that the primary driver of recovery kinetics was intracellular LC degradation (49% of T₈₀ variance), while BS-modulated extracellular parameters collectively contributed less than 20%. These findings indicate that BS does not reverse the molecular action of BoNTA but may transiently influence recovery kinetics via non-receptor-mediated pathways such as increased membrane permeability or altered vesicular trafficking. The magnitude and variability of this effect do not support the notion of a true pharmacologic reversal. Instead, these results emphasize the need for mechanistic scrutiny when evaluating rapid-reversal claims, particularly those propagated through anecdotal or social media channels without supporting biological plausibility. Full article

Calcium-dependent protein kinases (CDPKs) are key Ca²⁺ sensors in plants, mediating responses to abiotic stresses via phosphorylation signaling. In the halophyte Nitraria sibirica, which thrives in saline soils, we identified 19 CDPK genes (NsCDPKs) and classified them into four canonical angiosperm clades, highlighting conserved functional modules. Promoter analysis revealed diverse cis-acting elements responsive to light, hormones (ABA, MeJA, auxin, GA, SA), and abiotic stresses (drought, cold, wounding), along with numerous MYB binding sites, suggesting complex transcriptional regulation. Transcriptome profiling under salt stress (100 and 400 mM NaCl) showed induction of most NsCDPKs, with several genes significantly upregulated in roots and stems, indicating coordinated whole-plant activation. These salt-responsive NsCDPKs were also upregulated by cold but repressed under PEG-simulated drought, indicating stress-specific regulatory patterns. Fifteen MYB transcription factors, differentially expressed under salt stress, were predicted to interact with NsCDPK promoters, implicating them as upstream regulators. This study identified a potential salt- and cold-responsive CDPK regulatory module and a MYB-mediated transcriptional hierarchy in N. sibirica, providing insights into the molecular mechanisms of salinity adaptation and highlighting candidate genes that could be explored for improving salt tolerance in crop species. Full article

The rapid proliferation of generative artificial intelligence (GenAI) in educational settings has created unprecedented opportunities for language instruction, yet empirical evidence regarding its efficacy in primary-level English as a Foreign Language contexts remains scarce, particularly concerning pre-service teachers’ implementation experiences during formative practicum periods. This investigation, conducted in a public school in a non-Anglophone country during the Spring of 2025, examined the impact of GenAI-driven gamified activities on elementary pupils’ English language competencies while exploring novice educators’ professional development trajectories through a mixed-methods quasi-experimental approach with comparison groups. Four third-grade classes (n = 119 individuals aged 8–9) in a public school were assigned to either ChatGPT-mediated voice-interaction games (n = 58) or conventional non-digital activities (n = 61) across six 45 min lessons spanning three weeks, with four female student-teachers serving as instructors during their culminating practicum. Quantitative assessments of grammar, listening comprehension, and pronunciation occurred at baseline, post-intervention, and one-month follow-up intervals, while reflective journals captured instructors’ evolving perceptions. Linear mixed-effects modeling revealed differential outcomes across linguistic domains: pronunciation demonstrated substantial advantages for GenAI-assisted learners at both immediate and delayed assessments, listening comprehension showed moderate benefits with superior overall performance in the experimental condition, while grammar improvements remained statistically equivalent between groups. Thematic analysis uncovered pre-service teachers’ progression from technical preoccupations toward sophisticated pedagogical reconceptualization, identifying connectivity challenges and assessment complexities as primary barriers alongside reduced performance anxiety and individualized pacing as key facilitators. These findings suggest selective efficacy of GenAI across language skills while highlighting the transformative potential and implementation challenges inherent in technology-enhanced elementary language education. Full article

To mitigate explosion hazards arising from hydrogen leakage and subsequent mixing with air, the injection of inert gases can substantially diminish explosion risk. However, prevailing research has predominantly characterized inert gas dilution effects on explosion behavior under quiescent conditions, largely neglecting the turbulence-mediated explosion enhancement inherent to dynamic mixing scenarios. A comprehensive investigation was conducted on the combustion behavior of 30%, 50%, and 70% H₂-air mixtures subjected to jet-induced (CO₂, N₂, He) turbulent flow, incorporating quantitative characterization of both the evolving turbulent flow field and flame front dynamics. Research has demonstrated that both an increased H₂ concentration and a higher jet medium molecular weight increase the turbulence intensity: the former reduces the mixture molecular weight to accelerate diffusion, whereas the latter results in more pronounced disturbances from heavier molecules. In addition, when CO₂ serves as the jet medium, a critical flame radius threshold emerges where the flame propagation velocity decreases below this threshold because CO₂ dilution effects suppress combustion, whereas exceeding it leads to enhanced propagation as initial disturbances become the dominant factor. Furthermore, at reduced H₂ concentrations (30–50%), flow disturbances induce flame front wrinkling while preserving the spherical geometry; conversely, at 70% H₂, substantial flame deformation occurs because of the inverse correlation between the laminar burning velocity and flame instability governing this transition. Through systematic quantitative analysis, this study elucidates the evolutionary patterns of both turbulent fields and flame fronts, offering groundbreaking perspectives on H₂ combustion and explosion propagation in turbulent environments. Full article

Background/Objectives: Comparative studies examining postoperative pain and cosmetic outcomes following single-port laparoscopic appendectomy (SLA) and three-port laparoscopic appendectomy (TLA) in pediatric patients with appendicitis have produced inconsistent results. We aimed to determine whether SLA offers practical benefits over TLA in terms of recovery-phase pain relief and long-term cosmetic satisfaction in pediatric patients. Methods: This prospective comparative study included children aged 15 years or younger who underwent laparoscopic appendectomy for uncomplicated acute appendicitis. The degree of pain reduction was compared between the SLA and TLA groups on postoperative days (PODs) 1, 2, and 7, both at rest and during coughing and ambulation, using the Visual Analog Scale for Pain (VASP). Global cosmetic satisfaction was assessed at 1 month and 3 years postoperatively using the Visual Analog Scale for Cosmesis (VASC). Scar perception was evaluated with the Patient and Parental Scar Assessment Scale (PSAS). The primary outcome was the degree of pain reduction during ambulation on POD7. The secondary outcome was global cosmetic satisfaction at 3 years. Propensity score matching (PSM) was used as a sensitivity analysis to control for baseline differences. Continuous variables were assessed for normality using the Shapiro–Wilk test. Results: Baseline characteristics were similar among 238 patients (127 SLA and 111 TLA). SLA resulted in significantly greater pain reduction during ambulation on POD7 (deltaVASP7_walk: −6.22 ± 2.60 vs. −5.06 ± 3.23, p < 0.01, mean difference = −1.16, Cohen’s d = 0.39). However, this difference did not reach the minimal clinically important difference (MCID) threshold of 1.3. PSM analysis with 82 matched pairs confirmed the results, with even larger effect sizes. At 3 years, the SLA group reported significantly higher cosmetic satisfaction (VASC: median 10 [9–10] vs. 8 [6–9], p < 0.001, r = 0.44), surpassing the MCID of 1.5. The TLA group scored worse in scar perception regarding color, stiffness, thickness, and irregularity. Mediation analysis indicated that 66% of the overall effect on cosmetic satisfaction was mediated by scar perception. Conclusions: Although SLA offers statistically significant yet clinically marginal benefits in early postoperative pain reduction, it provides substantial benefits in long-term cosmetic satisfaction compared with TLA in pediatric patients. Full article

This study explored how AI affects the sustainability of competitive advantage in the tourism and hospitality sector, with a particular focus on the mediating roles of digital culture and digital skills in the lens of the Technology Acceptance Model (TAM). Data were collected via a structured questionnaire distributed to a purposive sample of 488 managers and supervisors working in five-star hotels, travel agencies, and DMCs across Saudi Arabia. The findings revealed that AI has a significant direct effect on sustainable competitive advantage and also exerts strong positive effects on both digital culture and digital skills. In turn, both of these internal enablers significantly contribute to sustaining a competitive advantage. Mediation analysis further showed that both digital culture and digital skills partially mediate the relationship between AI and sustainable competitiveness. The study addresses a notable gap in tourism research by providing localized evidence from a market undergoing rapid transformation under Vision 2030, and, taken together, extends TAM to an organizational lens by demonstrating AI’s role in shaping culture and skills that underpin a durable advantage while pointing to actionable priorities—targeting high-value AI use cases, conducting capability audits, institutionalizing continuous learning through visible leadership and role-based upskilling, and embedding culture- and skills-oriented KPIs within AI governance. Full article

Using the “Policy Pressure-Innovation Alignment-Performance Transformation” theory, this paper looks at how ESG ratings, green innovation, and corporate dual-organizational performance are linked. This study uses a multi-period Difference-in-Differences (DID) model in conjunction with a conditional mediation effect model to examine how ESG ratings causally influence substantive green innovation, which in turn improves corporate financial and environmental performance. Regression results show that corporate ESG ratings have a big effect on the performance of both organizations. ESG ratings have a bigger effect on financial performance, while ESG scores have a bigger effect on environmental performance. Looking at the sub-dimensions shows that policy ratings have immediate effects on environmental performance and delayed effects on financial performance. The conclusion that the internalization response of corporate environmental costs is timely, while the market revaluation has a delayed transmission effect, holds true after being tested through parallel trend analysis and synthetic DID testing. More research shows that differences in ESG ratings hurt financial performance but help environmental performance. This means that differences in ESG ratings may lead to more real green innovation activities, which have a direct effect on the environment and, in the end, lead to bigger improvements in environmental performance. The moderating effect test shows that being aware of the environment makes substantive green innovation more focused on quality by making people feel responsible for their actions. Also, environmental management leads to more corporate green patents, which has resource displacement effects and makes green patent innovations less effective. Heterogeneity analysis shows that state-owned businesses use their institutional advantages to improve the “quality-quantity” of substantive green innovation, which helps their corporate green development performance. Declining businesses push for green innovation to fix problems that are already there, but mature businesses don’t like ESG rating policies because they are stuck in their ways, which stops them from making real progress in green innovation. This paper ends with micro-level evidence and theoretical support to solve the “greenwashing” problem of ESG and come up with “harmonious coexistence” policy combinations that work for businesses. Full article

This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich’s ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA. Full article

In the knowledge economy era, optimizing R&D team size is crucial for breakthrough innovation. Breakthrough technologies rely more on knowledge restructuring and technological leaps than general technologies do. However, it remains unclear whether breakthrough technology formation follows a simple “more people, more power” logic within technological systems. This work examines 35,955 patents in recommendation system technology to propose a relationship model between collaboration scale and breakthrough technological innovation based on patent data from the recommendation system field. It aims to elucidate how collaboration scale influences breakthrough technological innovation through knowledge restructuring, thereby providing theoretical support and practical guidance for enterprises, institutions, and governments in innovation activities to advance technological innovation. The findings reveal three key points: (1) The relationship between collaboration scale and breakthrough innovation is not linear but follows an inverted U-shaped curve; (2) Knowledge recombination significantly mediates this relationship, also exhibiting an inverted U-shaped pattern with collaboration scale; (3) The inverted U-shaped effect of collaboration scale on breakthrough innovation varies by country. The optimal thresholds are 14.058 entities for China, 57.151 entities for the United States, and 4.801 entities for Russia. This work breaks through the limitations of the traditional theoretical framework and constructs a three-dimensional analysis framework of “collaboration scale → knowledge recombination → breakthrough technological innovation”. By introducing the mediating variable of knowledge recombination, this paper reveals the mechanism of R&D team size on radical innovation. It provides a theoretical basis for the construction of an innovation team and provides a theoretical basis for enterprises, governments, and institutions. Full article

Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood. Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation. Results: Prostate-specific antigen (PSA)—the clinically widely used blood biomarker for PCa—emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3′-untranslated region (3′-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues. Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone. Full article

Protein palmitoylation, a key post-translational modification (PTM) regulating protein transport and function, is catalyzed by palmitoyl transferases (PATs). PATs play vital roles in plant growth, development, and stress responses, yet their characterization in citrus remains limited. This study identified 23 PAT genes (CitPATs) possessing the conserved DHHC domain in the citrus genome through comprehensive genome-wide analysis. Analysis revealed that most CitPAT proteins are hydrophilic, basic, and stable, with significant variations in sequence length. Gene structure and motif analysis confirmed 10 conserved motifs, with the DHHC domain being the most conserved among all 23 members. The CitPAT genes were unevenly distributed across nine chromosomes and exhibit high evolutionary conservation. Promoter analysis identified numerous cis-acting elements associated with abiotic stress and hormone responses, including basic regulatory elements, light-responsive elements, and stress-responsive elements, with light-responsive elements being predominant. Expression profiling during fruit development revealed distinct correlation patterns with citric acid dynamics: CitPAT6, CitPAT18, and CitPAT23 showed positive correlations with acid accumulation, while CitPAT1, CitPAT10, and CitPAT13 exhibited negative correlations. Further RT-qPCR experiments revealed that CitPAT1 and CitPAT10 consistently demonstrated strong negative correlations with citrate content throughout fruit development. This functional diversification suggests roles in regulating citric acid metabolism. These findings provide novel insights into quality formation in facility-cultivated citrus and establish a foundation for understanding PAT-mediated regulation of fruit development. Full article

Organic manure and grass mulching are widely recognized as modifiers of soil microbial communities and nutrient dynamics; however, the combined effects of these practices on nitrogen fractionation and microbial functionality in orchard ecosystems remain poorly understood. This study conducted a comprehensive evaluation of soil nitrogen fractions, enzymatic activity, microbial diversity and functional traits in walnut orchards under three management practices: organic manure (OM), grass mulching combined with manure (GM), and chemical fertilization (CF) in China’s Loess Plateau. The results revealed that OM and GM significantly enhanced soil nutrient pools, with GM elevating total nitrogen by 1.96-fold, soil organic carbon by 97.79%, ammonium nitrogen by 128%, and nitrate nitrogen by 54.56% relative to CF. Furthermore, the OM significantly increased the contents of total hydrolysable nitrogen, amino sugar nitrogen, amino acid nitrogen, ammonia nitrogen, hydrolysable unidentified nitrogen, non-acid-hydrolyzable nitrogen compared to the CF and GM treatments. Meanwhile, ASN and AN had significant effects on mineral and total nitrogen. The OM and GM had higher activities of leucine aminopeptidase enzymes (LAP), α-glucosidase enzyme, β-glucosidase enzyme (βG), and N-acetyl-β-D-glucosidase enzyme (NAG). Microbial community analysis revealed distinct responses to different treatments: OM and GM enhanced bacterial Shannon index, while suppressing fungal diversity, promoting the relative abundance of copiotrophic bacterial phyla such as Proteobacteria and Chloroflexi. Moreover, GM favored the enrichment of lignocellulose-degrading Ascomycota fungi. Functional annotation indicated that Chemoheterotrophy (43.54%) and Aerobic chemoheterotrophy (42.09%) were the dominant bacterial metabolic pathways. The OM significantly enhanced the abundance of fermentation-related genes. Additionally, fungal communities under the OM and GM showed an increased relative abundance of saprotrophic taxa, and a decrease in the relative abundances of potential animal and plant pathogenic taxa. The Random forest model further confirmed that βG, LAP, and NAG, as well as Basidiomycota, Mortierellomycota, and Ascomycota served as pivotal mediators of soil organic nitrogen fraction. Our findings demonstrated that combined organic amendments and grass mulching can enhance soil N retention capacity, microbial functional redundancy, and ecosystem stability in semi-arid orchards. These insights support the implementation of integrated organic management as a sustainable approach to enhance nutrient cycling and minimize environmental trade-offs in perennial fruit production systems. Full article