Search Results (567)

Extensive efforts have been undertaken by numerous researchers to control respiratory viruses across the domains of diagnosis, prevention, and treatment. In this study, we developed a niclosamide–polysaccharide nasal spray (NPNS) formulation based on xanthan gum (XG), a naturally derived polysaccharide, and niclosamide, a conventional anthelmintic agent. We then evaluated its therapeutic efficacy following intranasal administration under influenza virus-infected conditions. NPNS was assessed for cytotoxicity under Good Laboratory Practice (GLP) conditions in accordance with ISO 10993-5, and no cytotoxic effects were observed. In influenza virus-infected human nasal epithelial cells (HNEc), NPNS treatment resulted in at least 92.5% suppression of viral gene expression. Furthermore, NPNS demonstrated significantly greater antiviral activity compared to Placebo 1 and Placebo 2, which were formulated by excluding niclosamide and XG, respectively. Owing to the physicochemical properties conferred by XG, NPNS exhibited prolonged retention on the nasal mucosa in a mouse model. Consistently, NPNS showed potent antiviral efficacy in influenza-infected mice. In addition, NPNS treatment was associated with the downregulation of S-phase kinase-associated protein 2 (SKP2), a host factor known to facilitate intracellular viral replication. Collectively, these findings suggest that NPNS may serve as a first-line protective barrier during the early stage of influenza infection by simultaneously blocking viral entry and suppressing viral replication through its dual physicochemical and molecular mechanisms. Full article

The escalating global threat of antimicrobial resistance (AMR) has intensified efforts to identify safe, effective, and sustainable alternatives to in-feed antibiotics in livestock production. The bovine gastrointestinal microbiome plays a central role in host immunity, nutrient utilization, and disease resilience, positioning microbiome-modulating interventions as promising candidates for antimicrobial stewardship. Despite growing experimental interest, a systematic synthesis of the available evidence in cattle is lacking. This systematic review aimed to evaluate the efficacy of microbiome-modulating interventions, including probiotics, prebiotics, postbiotics, phytogenic feed additives, essential oils, organic acids, and native rumen microbial supplements, as strategies to reduce antimicrobial use in cattle, and to characterize their effects on gut microbial diversity, fermentation characteristics, and host health and performance outcomes. A systematic search of Scopus, Web of Science, and EBSCOhost (including Academic Search Ultimate, MEDLINE with full text, and CAB Abstracts with Full text) was conducted in accordance with PRISMA guidelines. Studies were eligible if they used cattle (dairy cattle, beef cattle, calves, or mixed production systems), employed a microbiome-modulating intervention, and reported at least one microbiological or host outcome. Seventeen peer-reviewed studies published between 2010 and 2025 were included after full-text screening. Risk of bias was assessed using an adapted SYRCLE tool, which identified moderate overall study quality; the majority of included studies were randomized controlled trials or controlled experiments, though reporting of allocation concealment and blinding was inconsistent across studies. Across the 17 included studies, five broad categories of interventions were evaluated: probiotics (n = 5 studies), prebiotics (n = 2), postbiotics and organic acids (n = 4), phytogenic additives and essential oils (n = 4), and native rumen microbial supplements (n = 2). Animals spanned neonatal dairy calves, weaned Holstein calves, dairy heifers, lactating dairy cows, and Bos indicus feedlot beef cattle. Probiotics and organic acids most consistently improved growth performance: benzoic acid supplementation increased average daily gain by 8.4% (p < 0.05) and fructo-oligosaccharide prebiotics elevated body weight at weaning by 6.7% (p < 0.01). Native rumen microbial supplements improved energy-corrected milk yield by up to 3.1% without increasing dry matter intake. Polyphenols and bile acids demonstrated the strongest immunological and disease-preventive effects, reducing calf mortality by approximately 40% and disease severity by approximately 35%, respectively. Microbiome analyses revealed intervention-dependent increases in microbial diversity and shifts toward taxa associated with improved fermentation efficiency, including enrichment of propionate-producing Prevotellaceae, butyrate-associated Ruminococcus, and hindgut Bifidobacterium. Rumen fermentation outcomes included reductions in the acetate:propionate ratio and ammonia-N concentrations and improvements in fiber digestibility of 3.6–4.4 percentage units in dairy cows. Phytogenic additives preserved microbial diversity without inducing broad-spectrum suppression, functioning primarily as microbiome stabilizers rather than direct antimicrobial replacements. This systematic review provides evidence that gut microbiome modulation may enhance growth performance, improve fermentation efficiency, and reduce disease susceptibility in cattle, thereby supporting antimicrobial use reduction across dairy, beef, and mixed production systems. Effect magnitudes varied substantially across intervention categories and production contexts, and study quality was moderate, underscoring the need for larger, pre-registered trials with standardized outcome reporting and direct antibiotic comparator arms. Probiotics, prebiotics, and bile acid metabolites showed the greatest potential as components of integrated antimicrobial stewardship strategies in cattle production. Full article

Immune checkpoint inhibitors targeting the PD-1 (Programmed Cell Death Protein 1)/PD-L1 (Programmed Death-Ligand 1) axis have transformed cancer therapeutics, yet their efficacy in gynecologic malignancies particularly high-grade serous ovarian carcinoma remains disappointingly limited. This therapeutic resistance stems from a highly orchestrated, multidimensional immunosuppressive tumor microenvironment (TME) characterized by the convergent actions of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and an inhibitory cytokine network (IL-10, TGF-β, VEGF). Emerging evidence positions TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domain) as a master checkpoint integrator that coordinately regulates CD8+ T-cell exhaustion, NK-cell dysfunction, and Treg-mediated suppression. Dual blockade of PD-1 and TIGIT represents a mechanistically rational strategy to dismantle this immunosuppressive fortress. This review synthesizes current understanding of the gynecologic TME architecture, delineates the molecular and cellular basis for TIGIT/PD-1 synergy, critically evaluates ongoing clinical translation efforts, and proposes an integrative framework leveraging spatial transcriptomics, single-cell resolution immunoprofiling, and patient-derived experimental models to accelerate biomarker-driven therapeutic development. Full article

Umbrella species can facilitate efficient biodiversity conservation, as their targeted protection effectively safeguards co-occurring species and entire ecosystems in conservation management. To verify Hainan gibbon (Nomascus hainanus) as an umbrella species for sympatric endangered species, this study evaluated the conservation efficacy of the Hainan four-eyed turtle (Sacalia insulensis) through multidimensional spatiotemporal analysis. By comparing the population data collected using cage-trapping methods from 2005 to 2025, the S. insulensis population in the Bawangling region of the Hainan Tropical Rainforest National Park has exhibited obvious recovery, from no initial records to 25 individuals (mean relative population density: 0.0404 individuals/cage-day). Its growth trajectory is closely linked to the continuous enhancement of conservation efforts for Hainan gibbons, confirming umbrella effects stemming from poaching suppression and habitat restoration. However, when compared with recent surveys in other park regions, significant spatial limitations were revealed that the mean relative population densities at Yinggeling (0.01 individuals/cage-day) and Diaoluoshan (0.0064 individuals/cage-day) were only 25.74% and 15.84%, respectively. Additionally, juveniles constituted only 12% of Bawangling’s population, indicating that while the umbrella strategy delivers meaningful conservation outcomes, supplementary targeted initiatives are still needed to improve efficiency in resolving the species reproductive bottlenecks (e.g., nesting habitat quality). Those findings demonstrate that umbrella species conservation can establish an ecological conservation force field; however, its effectiveness is constrained by unequal resource allocation and species niche differences. Future efforts should overcome the spatial and ecological limitations of single-species umbrella effects by using smart patrol networks, secondary umbrella species mechanisms, and dedicated management plans. Full article

This paper proposes a reinforcement learning-assisted active disturbance rejection control (ADRC) framework for a nonlinear quadrotor unmanned aerial vehicle (UAV). Conventional ADRC controllers are designed for the quadrotor altitude and attitude channels. To evaluate robustness under disturbance-intensive conditions, a composite external disturbance is injected into the roll-channel dynamics. A Deep Deterministic Policy Gradient (DDPG)-based adaptive tuning mechanism is integrated into the roll-channel ADRC for the nonlinear state error feedback (NLSEF) gain adaptation, while fixed-parameter ADRC is retained for the remaining three channels. Without requiring system linearization and prior knowledge of disturbance models, the reinforcement learning agent learns an optimal gain adaptation policy directly through interaction with the nonlinear roll subsystem. Quantitative simulations demonstrate superior roll-axis disturbance rejection, leading to 90% faster settling time, the root mean square (RMS) control effort being reduced by 5.1%, and a 7.6% peak input suppression compared to conventional ADRC. The learning-based adaptation maintains comparable tracking accuracy across all channels while significantly improving transient recovery and control smoothness in the most disturbance-sensitive axis, validating selective reinforcement learning integration for robust nonlinear quadrotor flight control. Full article

Piperine, the principal alkaloid of Piper nigrum, has gained attention as a multifunctional dietary compound with broad effects on epigenetic and transcriptional regulation in cancer and chronic diseases. Evidence shows that piperine modulates DNA methylation (↓ DNMT3B), histone acetylation (↓ HDAC activity), and microRNA networks (↑ miR-29c, ↓ miR-383), thereby reshaping key oncogenic and tumor-suppressive pathways. Beyond canonical epigenetic control, it can also stabilize G-quadruplex structures in promoters such as c-MYC, adding an architecture-based mechanism of transcriptional repression. Its dual redox behavior—antioxidant at low doses and pro-oxidant at higher doses—confers context-dependent selectivity, enabling oxidative stress–mediated apoptosis in tumor cells. Compared with other nutriepigenetic agents (curcumin, resveratrol, EGCG), piperine stands out for its multi-target profile and preliminary evidence of activity against cancer stem cell–like phenotypes. Nonetheless, limited solubility, rapid metabolism, and scarce in vivo validation constrain clinical translation. Future efforts should focus on advanced formulations, multi-omics approaches, and cancer stem cell models to better define its therapeutic potential and safety. Full article

Although apartheid ended in 1994, its legacy continues to shape South Africa’s higher education system, reinforcing disparities in access, funding, and representation. This study aims to critically examine how apartheid diplomacy has influenced higher education and asks: how do its strategies continue to shape academic practices, institutional relationships, and systemic inequalities in post-apartheid South Africa? It conceptualises apartheid diplomacy as the use of education to entrench racial hierarchies, reproduce class domination, and suppress indigenous knowledge. Grounded in Marxist and Weberian class theories and Crenshaw’s intersectionality framework, the analysis traces how apartheid-era policies institutionalised systemic inequalities and how these legacies persist within institutions. A scoping review was conducted using five databases (EMBASE, APA PsycINFO, Cochrane Library, CINAHL, and Scopus) between January 2007 and April 2025, guided by PRISMA ScR and Arksey and O’Malley’s six-stage framework. Of 75 articles retrieved, 15 met the inclusion criteria. Findings reveal that apartheid diplomacy shaped academic governance, resource distribution, and knowledge production, leaving enduring inequities despite ongoing reforms. Transformation efforts, including financial aid schemes, equity policies, and curriculum debates, have achieved progress but remain constrained by structural, cultural, and intersectional barriers. The study underscores that achieving lasting equity requires continuous policy interventions, inclusive leadership, and curriculum decolonisation, alongside advocacy and interdisciplinary research. It reframes higher education as a diplomatic arena where equity and epistemic justice are negotiated, offering an original lens for understanding and dismantling apartheid’s enduring influence on South African academia. Full article

Under severe flight conditions such as high Mach number and large angle of attack, the aerodynamic environment of guided rockets exhibits highly nonlinear and strongly coupled characteristics. Significant dynamic coupling effects exist among the pitch, yaw, and roll channels, and aerodynamic parameters are subject to considerable uncertainties due to shocks, flow separation, and other factors. These issues collectively pose serious challenges to traditional control design methods based on linearized models. To address these challenges, this paper proposes a variable-gain adaptive decoupling control method. First, based on the classical feedforward decoupling concept, a decoupling controller is designed to preliminarily suppress inter-channel coupling effects. To further cope with aerodynamic parameter perturbations and model uncertainties, a model reference adaptive control framework is introduced, and an online parameter compensation mechanism is constructed to adjust controller parameters in real time according to changes in the aerodynamic environment. Additionally, by defining and estimating a system coupling degree in real time, a variable-gain adaptive law based on coupling degree is designed. This allows the decoupling effort to be dynamically adjusted according to the coupling degree, ensuring effective decoupling while avoiding performance degradation due to over-compensation. Simulation experiments conducted under typical high-dynamic flight scenarios demonstrate that, compared to traditional methods, the proposed approach effectively suppresses inter-channel coupling disturbances and significantly enhances system stability and robustness under parameter uncertainties and external disturbances. This provides a feasible technical solution for controlling guided rockets under extreme aerodynamic conditions. Full article

Cultivating and strengthening agricultural new quality productive forces (ANQPF) has become a key pathway for driving high-quality agricultural development (HQAD), ensuring food security, and advancing agricultural modernization. To investigate the spatiotemporal evolution and underlying mechanisms linking ANQPF and HQAD in the Tuojiang River Basin, this study employs panel data from 37 counties in the Tuojiang River Basin over the period 2011–2020. The entropy method and the DEA-BCC model are used to measure the levels of ANQPF and HQAD, while the fixed effects model, the mediating effect model, and the spatial econometric model are applied to examine the mechanisms through which ANQPF affect HQAD. The findings indicate the following: (1) The level of ANQPF is relatively low but has shown continuous growth, whereas the level of HQAD is relatively high but exhibits considerable fluctuation. Moreover, both dimensions display uneven development across regions. (2) ANQPF significantly promote HQAD at the 1% level, with agricultural technology development and green development serving as mediating mechanisms. However, a suppression effect is identified in agricultural technology development, and ANQPF exhibit a short-term inhibitory effect on agricultural green development. (3) Heterogeneity analysis indicates that the promoting effect of ANQPF is statistically significant in upstream and downstream regions but is not yet significant in the midstream region. (4) Further analysis reveals that ANQPF have a significant positive effect on HQAD within local regions. However, the spatial spillover effect across regions has not been fully realized. Therefore, to better leverage ANQPF in advancing HQAD, efforts should focus on addressing the challenges of agricultural technology extension and implementation, and on fostering new agricultural business entities. A special subsidy mechanism should be established with green transition as the guiding orientation to alleviate ecological protection pressure in the early stages of agricultural development. With regional coordination as the overarching goal, differentiated support policies should be implemented to promote overall basin development. Full article

Cross-border e-commerce offers consumers broader product access, yet uncertainty surrounding returns continues to suppress online purchase decisions. This study conceptualizes digital local return services as a digital assurance mechanism in cross-border e-commerce rather than merely a reverse logistics function. Drawing on UTAUT2, perceived risk theory, and trust theory, we develop and test a research model using survey data from South Korean consumers with prior experience of digital local return services (LRS). Structural equation modeling (SEM) is used to test the proposed relationships, and artificial neural networks (ANN) are employed to capture nonlinear effects and compare the relative importance of key predictors. Qualitative interview evidence is further incorporated to enrich the interpretation of the findings. The results show that performance expectancy, effort expectancy, facilitating conditions, and hedonic motivation significantly reduce perceived risk. Perceived risk, in turn, exerts a strong negative effect on purchase intention and weakens consumer trust. Additional ANN results indicate that hedonic motivation and facilitating conditions are particularly influential in lowering perceived risk, while perceived risk is more important than trust in predicting purchase intention. These findings show that digital return service design shapes consumer decisions primarily through risk reduction rather than trust enhancement alone. The study contributes to digital commerce research by explaining how return service design functions as a customer-facing platform assurance mechanism that improves conversion in cross-border online retailing. Full article

Background/Objectives: The Naxi people in Northwest Yunnan of China have used alcohol-soaked Pleione Pseudobulbus, which is the Pseudobulbus of Pleione bulbocodioides Rolfe (PBR), for lung diseases and tumors for a long period of time. This study aims to explore underlying mechanisms of bioactive ingredients in PBR, as well as to underscore the synergy between traditional medicine and modern pharmacological research. Methods: We verified the anti-tumor effects of the PBR extract through in vitro cell experiments, and explored its underlying mechanisms by combining untargeted metabolomics with network pharmacology to predict the related targets. Results: The anti-tumor potential of PBR extracts was systematically evaluated by integrating chemical profiling with in vitro cell-based assays. Untargeted metabolomics tentatively annotated metabolites spanning 12 major chemical classes, several of which have been previously reported to possess anti-tumor activity. To validate these annotations, prioritized candidates were further examined by LC-MS/MS against authentic reference standards at the nanogram scale, which confirmed the presence of sclareol—a naturally occurring diterpene with documented anti-tumor properties—as a constituent of PBR. Consistent with this chemical evidence, the PBR extract exerted multi-faceted anti-tumor effects in A549 lung cancer cells: it significantly suppressed proliferation, migration, and invasion; induced G0/G1-phase cell-cycle arrest; disrupted mitochondrial membrane potential; and modulated the expression of apoptosis-related proteins. Conclusions: By highlighting the pharmacological properties of cultivated PBR, we identified 118 overlapping targets between PBR compounds and lung disease-related targets, and we further selected 25 core lung cancer targets with high topological importance. This study suggests that the primary active compounds of Pleione bulbocodioides (Franch.) Rolfe may exert anti-lung cancer activity, potentially through targeting the EGFR tyrosine kinase inhibitor resistance pathway and the PI3K-Akt signaling pathway. Furthermore, in silico molecular docking suggested that the two major active compounds exhibited favorable predicted binding affinities with four core targets, particularly EGFR and AKT1, providing a basis for further experimental validation. These results support the potential value of Naxi traditional medicine and the need to further research onthese medicinal plants, thereby promoting Chinese herb medicine conservation efforts in the Naxi region. Full article

Recurrent wheezing represents a significant cause of respiratory morbidity in preschool children. While viral infections in the context of immune dysregulation are primary drivers, gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are increasingly recognized as critical triggers. The link between GERD and respiratory symptoms has historically been controversial; however, recent advances necessitate a re-evaluation of this relationship. This review critically analyzes the pathophysiological nexus between reflux and airway hyperresponsiveness, emphasizing the dual mechanism of microaspiration and vagal reflex, while integrating the concept of reverse causality (where respiratory effort actively exacerbates reflux). We highlight that the “respiratory reflux” phenotype in preschoolers is often characterized by non-acid and proximal episodes, which standard pH-metry fails to detect. Consequently, we discuss the diagnostic shift towards multichannel intraluminal impedance-pH (MII-pH) monitoring and the incorporation of novel metrics defined by the Lyon Consensus 2.0 (MNBI, PSPW index), alongside specific biomarkers such as pepsin. Finally, we propose a phenotype-driven management algorithm, differentiating between acid-suppressive therapy and alginate-based interventions, to mitigate disease burden and improve clinical outcomes in refractory cases. Full article

Thermal runaway (TR) remains a critical bottleneck for the safe application of lithium-ion battery (LIB) in large-scale energy storage systems, arising from the instability of battery materials under high temperatures. This review systematically summarizes materials design strategies to suppress TR, focusing on modifications of cathodes, anodes, separators, and electrolytes. For cathodes, surface coating and bulk doping enhance the structural stability and thermal decomposition temperature of high-Ni materials, while nanoscale engineering and carbon networks improve the electronic conductivity and interfacial stability of LiFePO₄ (LFP). For anodes, surface modification of graphite suppresses solid-electrolyte interphase degradation, and nanostructured silicon-based composites mitigate thermal failure caused by volume expansion. Separator functionalization, including ceramic coating, inorganic separators, and thermal shutdown separators, enhances thermo-mechanical stability and enables thermally triggered ion blocking. Flame-retardant electrolytes incorporate phosphorus-based, organosilicon, and halogenated additives that act through combined gas- and condensed-phase mechanisms. The review further discusses challenges in interfacial compatibility, system integration, and trade-offs among multiple performance metrics. Future efforts should focus on integrating intrinsic thermal stability with smart safety functions to achieve both high energy density and inherent safety. This review provides a systematic reference for the design and industrialization of high-safety materials for LIBs. Full article

Invasive marine crustaceans present ecological and socio-economic challenges, particularly where high fecundity, behavioural plasticity, and environmental tolerance limit the effectiveness of conventional control measures. The Atlantic blue crab, Callinectes sapidus, has expanded across the Mediterranean, where it exerts strong predatory pressure on native species and aquaculture resources, yet management efforts rely largely on traditional baited trapping. Drawing on extensive evidence from the global management of the European green crab, Carcinus maenas, we evaluate why conventional trapping has failed to achieve sustained population suppression in invasive brachyuran crabs. We synthesise lessons from green crab control to identify common biological and operational constraints, including rapid compensatory population responses, bycatch, and limited behavioural selectivity. We then examine the potential of semiochemical-based strategies—incorporating olfactory cues—within an integrated pest management (IPM) framework. Semiochemical-enhanced approaches offer the capacity to directly exploit species-specific sensory ecology, improve trap selectivity, and reduce non-target impacts, addressing fundamental limitations of existing methods. We argue that prioritising such IPM, rather than further optimisation of traditional trapping alone, represents the most realistic pathway for long-term mitigation of C. sapidus in the Mediterranean. While eradication remains improbable, strategically deployed semiochemical-based control could substantially enhance suppression efficiency and inform broader invasive species management. Full article

Human papillomavirus (HPV) is one of the most widespread sexually transmitted infections globally, whose persistent infection plays a major role in causing cervical cancer. Vaccination is therefore a key prevention strategy. Using a gender-stratified dynamic transmission model tailored to a Tunisian case, we investigate the impact of bivalent HPV vaccination. The proposed model accounts for partial cross-immunity and captures both direct and indirect effects of female-only vaccination. We derive the basic reproduction number and the corresponding herd immunity threshold, and a global sensitivity analysis shows that vaccine coverage, efficacy, and cross-protection are strong drivers of transmission reduction. Their combined effects on disease spread are quantified by varying these parameters across biologically relevant ranges. An optimal control problem was formulated and analyzed using Pontryagin’s Maximum Principle to minimize persistent infections and cancer cases while limiting vaccination effort. Three vaccination scenarios are compared: an ideal case with full vaccine availability and two resource-constrained cases with respective maximum coverage rates of $100\%$ and $80\%$. The numerical simulations revealed that the optimal strategy under unconstrained conditions can achieve significant suppression of infection, persistence, and cancer. Under constrained effort, the optimal control still achieves substantial reductions in disease burden, with minor differences in dynamics and speed of immunity buildup. Our results highlight the effectiveness of female-only HPV vaccination in providing both direct and indirect protection. They also emphasize the importance of sustained coverage in constrained settings. Full article