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Gentiopicroside attenuates pharyngeal inflammation in rats by inhibiting MUC5AC production associated with the COX-2/PGE2 signaling pathway
The association between interhospital transfer and sepsis guideline adherence among rural emergency department patients
Introduction The objective of this study was to assess whether interhospital transfer delays completion of the Surviving Sepsis Campaign (SSC) 3-hour bundle among rural sepsis patients. Methods We conducted a multicenter (n = 23) cohort study among adult rural sepsis patients in an ED-based telemedicine network between August 2016 and June 2019. The primary exposure was interhospital transfer and the primary outcome was completion of the SSC 3-hour bundle. Secondary outcomes included SSC component adherence, ED length-of-stay, and in-hospital mortality. We used a Cox proportional hazards model to evaluate time to bundle completion by transfer status, generalized linear models for dichotomous outcomes, and linear and quantile regression for ED length-of-stay. Results A total of 1,191 patients were treated in participating hospitals, with 359 (30%) undergoing interhospital transfer. SSC bundle adherence was similar in both groups (difference 2.2%; 95% confidence interval [CI]: – 2.2, 6.5%). Among eligible patients, transfer was associated with a longer ED length-of-stay (3.1 hours vs 2.6 hours; difference 0.6 hours; 95%CI: 0.4, 0.7).
Genomic insights from the Malaysian Pangasiid, Pangasius nasutus, reveal evolutionary divergence and functional adaptations in Pangasiid catfishes
Abstract Pangasius nasutus (Bleeker, 1863), locally known as ‘Patin buah’, is a commercially valuable freshwater catfish native to Peninsular Malaysia. Unlike the commonly farmed pangasiids Pangasianodon hypophtalmus , Pangasius djambal and P. sanitwongsei , P. nasutus is prized for its firmer texture, lower fat content, and distinctive flavour, making it a premium aquaculture species. Despite its ecological and economic importance, wild populations have declined significantly owing to overfishing and habitat modification, with limited genomic information available to date. Here, we present the first genome of P. nasutus generated using a hybrid Illumina-PacBio sequencing approach. The assembled genome spans 822.3 Mb with a scaffold N50 of 12.9 Mb and 98.6% BUSCO completeness, representing one of the most complete assemblies within the Pangasiidae. Gene annotation predicted 25,987 gene models, of which 89.1% were classified as complete based on BUSCO assessment. Comparative genomic analysis with P. djambal , P. gigas , and P. hypophtalmus revealed a large conserved orthogroup core alongside 198 unique orthogroups specific to P. nasutus . Functional enrichment of these species-specific genes indicated significant overrepresentation of chemosensory perception, G-protein-coupled receptor signalling, immune system processes, and reproductive and developmental pathways, suggesting genomic innovations linked to feeding ecology, environmental adaptation, and reproductive synchronisation in variable riverine habitats. Phylogenomic reconstruction based on single-copy orthologs confirmed the deep divergence between Pangasianodon and Pangasius , with P. nasutus forming a robust sister clade to P. conchophilus . This topology is congruent with previous mitogenomic studies of pangasiids, reinforcing the evolutionary coherence and taxonomic validity of the genus Pangasius . Overall, the genome of P. nasutus provides a foundational resource for functional, comparative, and conservation genomics of Malaysian pangasiids. It offers critical insights into the evolutionary history and adaptive diversification of the family Pangasiidae and lays the groundwork for future breeding, management, and genomic monitoring initiatives for native freshwater fishes.
Identifying the educational needs of nurses caring for adults with congenital heart disease: A scoping review protocol
Objective The objective of this scoping review is to answer the question, “What is the existing evidence on nurses’ educational needs in caring for adults with congenital heart disease?” by identifying and summarizing research and grey literature on the educational needs of nurses who care for this population. Methods The scoping review will use the Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) for reporting. Five databases will be searched: Medline, Embase, CINAHL, ERIC, and Scopus. Grey Matters, Google, and thesis and dissertation databases will be used to identify relevant grey literature. All types of published articles and non-empirical research will be included with no temporal, geographical, or language restrictions. Two independent reviewers will screen titles and abstracts, engage in full-text screening, and perform data extraction in Covidence. Any disagreements will be resolved through a third reviewer. Results The results of the scoping review will be analyzed using descriptive statistics and narrative analysis. The results will be reported using tables and figures. Findings will be disseminated through a manuscript and at conferences. Conclusion The findings of this scoping review aim to inform future research and interventions on the nursing care of adults with congenital heart disease. Registration The scoping review was registered on Open Science Framework ( https://osf.io/4t5hr ) on December 5, 2025.
Toxicity of diet-incorporated silica nanoparticles on the invasive fall armyworm, spodoptera frugiperda (lepidoptera: noctuidae): life table and population projection analysis
Leadership, teamwork and work outcomes in healthcare: A test of a model
Effective teamwork in healthcare improves patient outcomes, staff well-being, and service delivery. To enhance these benefits, NHS teams should implement targeted leadership training, routinely assess and clarify roles to reduce ambiguity, and encourage staff participation in decision-making to boost autonomy. Researchers analysed 2022 and 2023 NHS Staff Survey data using Structural Equation Modelling. Main findings: (1) Effective leadership boosts teamwork and, in turn, engagement and well-being; (2) Teamwork can raise role ambiguity and lessen autonomy, leading to stress; (3) Leadership is key to managing these issues. Thus, boosting autonomy and reducing ambiguity support better team performance and staff well-being. The study highlights the need for leadership programmes to strengthen team dynamics and reduce uncertainty.
Design, synthesis, biological assessment, and integrated computational analysis of new pyrazole-based antimicrobial candidates
Abstract The emergence of antimicrobial resistance needs the development of new chemotherapeutic scaffolds. Pyrazole derivatives are recognized for their broad biological activity; however, further structural innovation is required to enhance antimicrobial efficacy and safety. Thus, new pyrazole-based candidates were designed and synthesized using 3-(4-chlorophenyl)-1-phenylpyrazol-4-yl-2-cyanoacryloyl chloride as a versatile precursor. A series of mono- and bidentate nucleophile-derived compounds was prepared and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria and Candida albicans . Several derivatives exhibited potent antibacterial and antifungal activity, particularly against Gram-positive strains, with minimum inhibitory concentrations comparable to standard drugs. Most compounds showed low cytotoxicity toward HepG2 cells, which was further reduced upon antioxidant co-treatment. Notably, vitamin C and N -acetylcysteine showed synergistic enhancement of antimicrobial and antibiofilm effects. Molecular docking studies against dihydropteroate synthase (DHPS, PDB: 5U0V) revealed favorable binding interactions, with the thiophene-based derivative 10 displaying ligand efficiency comparable to the co-crystallized ligand 7VJ. Overall, these findings highlight pyrazole-based scaffolds as promising antimicrobial candidates with favorable biological profiles, providing a strong basis for further structural optimization.
Understanding barriers and facilitators to cervical cancer prevention among young Korean Women: A focus group interview study
Cervical cancer is a largely preventable and controllable disease. Social perceptions regarding sexual experiences and gynecological visits contribute to stigma, which serves as a major barrier to screening and human papillomavirus vaccination. This study explored how stigma is formed and reinforced within sociocultural norms and personal psychological barriers. Focus group interviews were conducted with 14 Korean women aged 20–29 years, divided into screeners and non-screener groups, on November 23, 2024. Based on the transcriptions, Thematic analysis was performed on the transcripts to organize codes into core themes,(in compliance with qualitative research reporting standards). A total of 28 codes were grouped into 10 sub-themes and classified by group. Among them, three sub-themes were common to both screeners and non-screeners, including negative perceptions of gynecological visits, stigma associated with sexually transmitted diseases, and barriers due to a lack of information. Among screeners, four sub-themes were identified: a desire for alternative notification methods for screening, psychological barriers to screening, a sense of burden from additional tests during visits, and reluctance to share screening experiences due to perceived prejudice from others. Among non-screeners, three sub-themes were identified: stigma toward patients with cervical cancer and lack of awareness of the sensitivity of cervical cancer. To promote cervical cancer preventive behaviors, stigma must be addressed as a social process rather than solely an individual issue. Practical solutions include creating a predictable screening environment (e.g., prior notification of procedures and additional tests with consent), improving patient-centered care, and enhancing notification methods. This study provides a foundation for developing stigma-related indicators and designing follow-up studies. (e.g., individual interviews/large-scale surveys).
Multi-target regulation mechanisms of systemic lupus erythematosus, a network pharmacology and molecular docking study on active compounds from Artemisia argyi
Abstract Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by persistent immune activation and multi-organ damage. In this study, we integrated network pharmacology, molecular docking, and in vitro validation to identify and prioritize the active compounds, targets, and regulatory pathways of Artemisia argyi (AA). We identified nine candidate active compounds of AA and 380 predicted protein targets. Intersecting these with 218 SLE-associated genes yielded 19 overlapping targets, among which IL2, CASP3, ACE, PPARG, HSP90AA1, and ANXA5 exhibited the highest network connectivity. Functional enrichment analyses highlighted key pathways, including leukocyte activation, IL-17 signaling, and Th17 cell differentiation. Molecular docking revealed favorable binding affinities of quercetin and naringenin with several core targets. Among these, peroxisome proliferator-activated receptor gamma (PPARG) was selected for exploratory validation based on its high network centrality, favorable docking profile, characterized by strong binging affinities (<-5.5 kcal/mol) for both quercetin and naringenin. Subsequent bioinformatic screening identified LTF, CD72, IL13, CHI3L1, and TLR9 as putative SLE-associated genes regulated by PPARG. Experimentally, AA water extract (AAW) upregulated the expression of PPARG and these downstream genes in THP-1-derived macrophages, whereas pharmacological inhibition of PPARG significantly attenuated these effects. These findings suggest that AA modulate PPARG-dependent transcriptional signaling in immune cells, presenting a candidate mechanism that warrants further validation in disease-relevant models.
Correction: Assessing body position through experimental cremation: A pilot study using colorimetry and FTIR-ATR analyses
Transdiagnostic behavioral and sociodemographic influences on the cognitive-adaptive functioning gap in neurodivergent children
Distinct roles of neuronal phenotypes during neurofeedback adaptation
Learning adaptation allows the brain to refine motor patterns in response to changing environments rapidly. While population-level neural dynamics and single-neuron activity in motor learning have been widely studied, the contributions of individual neuron types remain poorly understood. Here, we employed a brain-machine interface (BMI) task with perturbations of varying difficulty to investigate single-neuron dynamics underlying neurofeedback adaptation in two rhesus macaques. Cortical neurons were classified based on waveform shape into narrow waveform (NW) and broad waveform (BW) categories, representing putative inhibitory interneurons and excitatory pyramidal neurons, respectively. Compared to BW neurons, NW neurons were more active and more strongly involved in the learning process. Moreover, task difficulty modulated neural responsiveness and coordination within both neuron groups, highlighting differential neuron engagement during neurofeedback adaptation. Our findings provide novel insights into single-neuron mechanisms underlying neurofeedback adaptation and emphasize the distinct functional roles of neuronal phenotypes in rapid learning processes.
TRPV4 modulates sperm motility and fertilization rate in chub mackerel
Abstract Achieving efficient fertilization in marine fishes remains a challenge for aquaculture, as the molecular mechanisms linking seawater-derived osmotic and ionic cues to sperm motility remain poorly understood. Here, we investigated the role of the mechanosensitive cation channel TRPV4 in sperm function of chub mackerel ( Scomber japonicus ), a commercially important species with recently established full life-cycle aquaculture. Quantitative PCR together with TRPV4 immunofluorescence suggested the presence of TRPV4 in sperm, predominantly localized to the midpiece and flagellum. Pharmacological activation of TRPV4 with RN1747 (100 nM) enhanced sperm motility by approximately 6% during the critical 30–50 s post-activation window ( p < 0.05), increased amplitude of lateral head displacement (ALH; p < 0.05), and elevated intracellular Ca 2+ levels approximately twofold ( p < 0.05). In contrast, TRPV4 inhibition with RN1734 (1 µM) reduced sperm motility by up to 95% and markedly impaired sperm kinematics and Ca 2+ dynamics. TRPV4 activation was also associated with increased fertilization and hatching rates, whereas inhibition nearly abolished both (< 1%). Our findings support an important role for TRPV4 in the regulation and maintenance of sperm motility following activation, likely through osmo–ionic and Ca 2+ -dependent signaling pathways. Together, these results extend previous findings from seabream to a scombrid species and suggest that TRPV4-associated sperm regulatory mechanisms may be broadly conserved among marine teleosts. These findings also highlight TRPV4 as a potential pharmacological target for improving fertilization efficiency in marine aquaculture.
Quantifying antimicrobial use and trends in commercial poultry and dairy farms in Bangladesh
Antimicrobial resistance (AMR) continues to be detected in bacteria from food producing animals in Bangladesh. Globally, as well as in many low- and middle-income countries (LMICs), antimicrobial use (AMU) is identified as the primary driver of rising AMR. This pilot study aimed to quantify AMU in poultry (broiler and layer) and dairy farms in Gazipur and Chattogram districts, assessing seasonal and species-specific AMU patterns. A longitudinal survey conducted during the summer and winter seasons of 2022–2023 involved 36 purposively selected farms (12 each broiler, 12 layer and 12 dairy). AMU was quantified using kilograms of antimicrobial active ingredients (AAIs) and milligrams per population correction unit (mg/PCU). AMU quantity was highest in layer farms (285.80 mg/PCU), followed by broilers (173.29 mg/PCU) and dairy farms (3.56 mg/PCU). Seasonal variations revealed lower AMU levels in broilers (125.68 mg/PCU) and layers (130.48 mg/PCU) in winter, whereas dairy usage increased in winter (13.93 mg/PCU). Predominantly used AAI’s included neomycin (broilers, both seasons), oxytetracycline (layers in summer), tylvalosin (layers in winter), sulfonamides (dairy in summer), and penicillin (dairy in winter). Poultry farms utilised substantially higher AMU quantities. Notable geographic differences in AMU quantities used in broiler and layer farms were observed, while dairy farms showed uniform use across districts. Of important public health concern is the high proportion (65–90%) of antimicrobials that fall under the World Health Organization’s (WHO) Medically Important Antimicrobial (MIA) categories, particularly Critically Important (CIA) or Highest Priority Critically Important Antimicrobials (HP-CIA), as well as the substantial use of Watch- and Reserve-group antimicrobials according to the WHO AWaRe framework. These findings highlight excessive use of medically important antimicrobials and emphasise the urgent need for regulatory action and improved stewardship. This pilot study provides essential baseline data for developing farm-level national AMU surveillance system in Bangladesh.
In vitro assays, probiogenomic analysis, safety assessment and probiotic potential of Enterococcus faecium F25
Adverse events following immunization during COVID-19 mass vaccination campaigns in the Democratic Republic of Congo: Findings from active safety surveillance
Introduction Post-marketing safety surveillance is essential for ensuring vaccine safety and maintaining public trust, particularly in African settings where evidence on the safety of COVID–19 vaccines remains limited. This study aimed to determine the overall incidence and types of AEFIs, as well as the factors associated with their occurrence, during COVI-19 mass vaccination campaigns in Democratic Republic of Congo. Methods From December 1–29, 2023, a prospective safety surveillance study was conducted in Kinshasa Province. Participants were surveyed through phone calls from day 1–28 following COVID-19 vaccine administration. AEFI incidence rates were calculated by type of vaccine, sex, number of dose and age group. Factors associated with AEFIs were identified using multivariable logistic regression models, expressed by adjusted odds ratio and its 95% confidence interval. Results The study included 4766 participants. Their median [IQR] age was 36 [27−48] years and 2503 (53%) were males, 94.63% received the J&J vaccine while 256 (5.37%) received the BNT162b2 vaccine. Incidence of AEFIs was 23.75% (95%CI: 22.54%−24.99%). AEFIs mostly reported were fever (9.61%, 95%CI: 8.88%−10.48%), injection site pain (9.00%, 95%CI: 8.20%−9.85%), headache (4.11%, 95%CI: 3.57%−4.72%), stiffness (1.51%, 95%CI: 1.18%−1.89%) and myalgia (1.15%, 95%CI: 0.87%−1.49%). The incidence of AEFIs was higher for the BNT162b2 vaccine at 34.48% (95% CI: 28.57%−40.54%) vs. 23.15% (95% CI: 21.92%−24.41%) for the J&J vaccine. Compared to participants aged 18−59 years, those under 18 years old were associated with decreased odds of reporting any AEFI (aOR= 0.26, 95%CI: 0.13–0.88) and injection site pain (aOR=0.18, 95%CI: 0.05–0.75). Those aged 60 years and older were associated with decreased odds of reporting any AEFI (aOR= 0.78, 95%CI: 0.62–0.99) and fever (aOR=0. 63, 95%CI: 0.43–0.92). Conclusions Approximately one-quarter of participants reported AEFI. The observed association with vaccine type and age underscores the need for systematic vaccine safety monitoring in the population. This is critical for guiding future vaccination strategies tailored to individuals who may be more susceptible to AEFIs.
Intelligent early warning model for financial risks of new energy vehicle enterprises based on deep learning
Abstract The financial stability of new energy vehicle (NEV) firms has become a central concern amid rapid digitalization and the transition toward low-carbon economies. Traditional financial risk models assume fixed structures and linear relationships, which makes them ineffective for handling the complex, time-varying, and policy-sensitive nature of energy firms. To address this challenge, a deep learning–based early warning framework is developed using the Modular Energy Accountability Lattice (MEAL) and the Semantic Policy Fusion Strategy (SPFS). These components jointly encode financial flows and policy dynamics to predict systemic risk. Experiments on real-world NEV firm data show that the proposed model achieves higher precision, recall, and interpretability than conventional methods, offering a scalable and policy-aware tool for sustainable financial monitoring.
Evolutionary patterns of the mitochondrial control region in vertebrates: A large-scale comparative analysis
The mitochondrial control region (CR) is the largest non-coding region in the vertebrate mitogenome and contains essential elements for replication and transcription. Despite its functional relevance, its evolutionary dynamics remain poorly understood. Here, we analyzed 5,235 complete vertebrate CRs spanning 11 classes to investigate how conserved sequences blocks (CSBs) and Extended Termination-Associated sequences (ETAS) shaped CR evolution. We hypothesized that CR length is positively associated with repeat accumulation, with tetrapods exhibiting longer and more complex CRs than fishes, while core elements remain conserved. Our analyses revealed marked inter- and intra-class variability, with longer CRs in tetrapods (1,283.27 ± 489.6 bp) than in fishes (969.25 ± 239.5 bp). Duplication events were restricted to tetrapods, especially birds and reptiles. Nucleotide composition was heterogeneous among orders, and structural divergence of CSBs was inferred across lineages. Repetitive elements were present in ~43% of CRs, with their abundance strongly correlated with CR length. Importantly, longer CRs were associated with higher GC content and greater variation in copy number of ETAS and CSBs. These results demonstrate that mitogenome CR expansion in vertebrates is largely driven by repeat proliferation, whereas key motifs required for replication and transcription are retained. We further identify lineage-specific trends, including pronounced CR elongation in amphibians and reptiles, contrasted with progressive reduction and simplification in birds and mammals. Our study provides the first comprehensive comparative framework of vertebrate CR evolution, highlighting how repetitive elements, conserved motifs, and nucleotide composition jointly contribute to both functional regulation and lineage-specific diversification.
Infusion of human mesenchymal stromal cells during normothermic machine perfusion of porcine kidneys: a randomized, blinded, preclinical study
Abstract Kidney transplantation from donation after circulatory death (DCD) donors is increasingly used but remains associated with warm ischemic injury. Normothermic machine perfusion (NMP) enables functional assessment and therapeutic interventions. Mesenchymal stromal cells (MSCs) display immunomodulatory and regenerative properties, yet their translational efficacy during NMP remains unclear. In a porcine model, six pairs of kidneys subjected to 30 min of warm ischemia followed by 3 h of static cold storage underwent 6 h of NMP. In each pair, one kidney randomly received an intra-arterial injection of placebo, while the contralateral kidney received 10 million clinical-grade human bone marrow–derived MSCs (hMSCs). Perfusion characteristics, glomerular filtration, tissue injury, and inflammatory markers were assessed. hMSC infusion during NMP was technically feasible and hemodynamically well tolerated, with no adverse effects on perfusion stability. Perfusion parameters, urine output, and creatinine/iohexol clearance showed no significant differences between groups. NGAL and cytokines levels increased during perfusion, but hMSCs did not alter their dynamics. Intra-arterial delivery of clinical grade hMSCs during NMP was safe but did not improve renal function or reduce histological injury. These results highlight the challenges of achieving MSC engraftment during ex situ perfusion and highlight the need for refined strategies such as repeated dosing, prolonged perfusion, or extracellular vesicle therapy. Despite the negative findings, this study presents a highly translational large-animal model, supporting further investigation of MSC-based therapies in human kidneys discarded for transplantation.