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Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age &#xf0b3;40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans

Diverse structures of mcr-10-bearing plasmids and high colistin resistance in Enterobacter cloacae complex clinical isolates from South Korea.

BACKGROUND: The emergence of mcr-mediated colistin resistance in Enterobacter cloacae complex (ECC) poses a significant threat to antimicrobial therapy. Among mcr variants, mcr-10 has been identified in various environments, but its genetic diversity, structural context, and functional role in colistin resistance remain unclear. METHODS: We investigated 183 ECC isolates and identified 60 colistin-resistant strains through minimum inhibitory concentration (MIC) testing. The presence of mcr-10 was screened using reference genomes from NCBI, and whole plasmid sequencing was conducted on mcr-10-positive isolates. The genetic environment of mcr-10 was analyzed via synteny and structural annotation. RESULTS: Whole-plasmid sequencing of eight mcr-10-positive ECC isolates identified three replicon types among the mcr-10-harboring plasmids: IncFIB (n=3), IncFII (n=3), and IncFII/IncFIB (n=2). Although all plasmids shared the xerC-mcr-10 cassette, they lacked a conserved backbone and showed diverse genetic contexts with variable insertion sequences near mcr-10, indicating marked structural heterogeneity. No additional antimicrobial resistance genes were detected on these plasmids. When introduced into E. coli DH5&#x3b1;, the plasmids increased colistin MICs only modestly, whereas representative plasmids transferred into colistin-susceptible E. roggenkampii and E. kobei conferred high-level resistance comparable to that of the parental mcr-10-positive isolates. Consistently, qRT-PCR showed higher mcr-10 expression in ECC transformants than in E. coli under colistin exposure, supporting a hostdependent effect on mcr-10-mediated colistin resistance. CONCLUSION: These findings highlight the diversity of mcr-10-carrying plasmids and suggest that mcr-10-mediated colistin resistance is shaped by the host genetic background. Further studies are needed to clarify the mechanisms underlying mcr-10 expression.

Colistin

Preoperative Patient Education on Opioid Use and Pain After Surgery: A Randomized Trial.

OBJECTIVE: To evaluate the impact of preoperative analgesic education on postoperative opioid consumption, pain scores, and patient satisfaction with analgesia. BACKGROUND: Effective postoperative pain management is crucial for patient recovery and satisfaction, yet opioid use poses risks of tolerance and addiction. Preoperative patient education offers a potential avenue to mitigate opioid reliance and improve pain management outcomes. METHODS: This single-center randomized trial was conducted at the Cleveland Clinic Main Campus between October 2021 and October 2023. Adult patients scheduled for hip arthroplasty or laparoscopic-assisted abdominal surgery with an ASA physical status of 1 to 4 were eligible. Patients with a history of prolonged opioid use, planned regional block or epidural analgesia, or limited English fluency were excluded. Participants were randomized 1:1 to receive either an analgesic educational video or a generic video about surgery and hospitalization. The primary outcome was opioid consumption during the initial 72 postoperative hours. Secondary outcomes included time-weighted average pain scores and patient satisfaction with analgesia. RESULTS: Among 957 analyzed patients, preoperative analgesic education did not significantly reduce opioid consumption (adjusted ratio of geometric means, 1.01; 95% CI, 0.86-1.18; P =0.890) or improve pain scores (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P =0.617). Patient satisfaction scores also did not differ significantly between groups (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P = 0.611). CONCLUSIONS: Preoperative analgesic education did not result in clinically meaningful reductions in opioid consumption or improvements in pain management outcomes. Further research may explore more intensive educational interventions to optimize postoperative pain management strategies.

Humans

Statistical test to compare the linkage model and the admixture model based on central limit results.

In the Admixture Model, the probability that an individual carries a certain allele at a specific marker depends on the allele frequencies in K ancestral populations and the proportion of the individual's genome originating from these populations. The markers are assumed to be independent. The Linkage Model is a Hidden Markov Model that extends the Admixture Model by incorporating linkage between neighboring loci. We prove consistency and asymptotic normality of maximum likelihood estimators for the ancestry of individuals in the Linkage Model, complementing earlier results by (Pfaff et al., 2004; Pfaffelhuber and Rohde, 2022; Heinzel, 2025) for the Admixture Model. These results are used to prove that a statistical test that allows for model selection between the Admixture Model and the Linkage Model is an asymptotic level-&#x3b1;-test. Finally, we demonstrate the practical relevance of our results by applying the test to real-world data from The 1000 Genomes Project Consortium (2015).

Genetic Linkage

Aflatoxins and their biosynthetic precursors in lotus seeds: simultaneous UPLC-MS/MS determination, contamination profiling, and matrix-specific accumulation during Aspergillus flavus infection.

Aflatoxin (AF) contamination poses a severe global threat to food and medicinal material safety, yet existing research focuses on terminal AF metabolites while neglecting residual biosynthetic precursors, leading to potential underestimation of contamination risks. In this study, a UPLC-MS/MS method was established for the simultaneous quantification of six AFs and their five precursors in lotus seeds, with optimization of mass spectrum parameters, chromatographic separation conditions, and sample pretreatment. Method validation confirmed linearity (R2&#xa0;>&#xa0;0.99), LODs (0.03-0.36&#xa0;&#x3bc;g/kg), and recoveries (76.53%-120.0%, RSD&#xa0;<&#xa0;15%). Analysis of 41 natural lotus seed samples revealed a 63.4% AF contamination rate, dominated by B-group AFs, while O-methylsterigmatocystin (OMST) and versicolorin hemiacetal (VOH) were identified as the primary co-residual precursors with co-occurrence rates &#x2265; 50%. Notably, AFM1 was predominantly detected in natural samples with AFB1 concentrations exceeding 100&#xa0;&#x3bc;g/kg. Artificial inoculation experiments further demonstrated that sterilization and sealing conditions modulated AF biosynthesis in lotus seeds, with non-sterilized and non-sealed groups showing delayed fungal metabolism and lower toxin accumulation. A significant linear correlation was observed between AFM1 and AFB1 levels (r&#xa0;=&#xa0;0.94) in infected samples, demonstrating their accumulation levels are coupled with fungal overall metabolic flux. Given the high co-occurrence rate of OMST/VOH with AFB1 in natural samples, their individual and combined toxicities require in-depth investigation. This work deciphers matrix-specific AF dynamics in lotus seeds, supporting regulatory standard refinement (e.g., precursor inclusion) and targeted control (e.g., time-sensitive drying after harvest). Further studies will focus on exploring the molecular mechanisms of substrate-dependent AF synthesis.

Aflatoxins

Efficacy and safety of microwave ablation for the treatment of pulmonary osteosarcoma oligometastases.

PURPOSE: Evaluate efficacy and safety of microwave ablation (MWA) for pulmonary osteosarcoma oligometastases. METHODS: Twenty-two patients (median age, 16&#x2009;years [range, 9-41&#x2009;years]; 15 male) with pulmonary osteosarcoma oligometastases who underwent MWA from January 2018 to December 2023 were included, with 27 MWA sessions for 36 lung metastases. Technical success and complications were evaluated in all 22 patients, while efficacy and survival were evaluated in 19 patients with 24 MWA sessions in treatment of 32 tumors. Technical success was assessed for each tumor. Local tumor control, progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Complications were classified using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Technical success was achieved in all 36 tumors (100.0%). Local tumor progression occurred in five of 32 tumors (15.6%). The estimated local tumor control rates at 12, 24 and 36&#x2009;months were 96.9%, 86.1% and 81.5%, respectively. No significant difference in local control was found between tumors &#x2264; 10&#x2009;mm and > 10&#x2009;mm (p&#x2009;=&#x2009;.470). Twelve of 19 patients (63.2%) developed new lung metastases outside the ablation area, including one with concurrent newly developed bone metastases and one with recurrence of primary osteosarcoma. The median PFS was 21.5&#x2009;months. The estimated OS rates at 12, 24 and 60&#x2009;months were 100.0%, 94.4% and 94.4%, respectively. Major complications occurred in five of 27 sessions (18.5%). CONCLUSIONS: MWA preliminarily demonstrates a high technical success rate, notable local tumor control, promising overall survival and acceptable safety for pulmonary osteosarcoma oligometastases.

Adolescent

Understanding and Usefulness of Effect Size and Certainty of Evidence: A Cross-Sectional Survey of Evidence-Based Practice Competencies Among US Registered Dietitians.

INTRODUCTION: Understanding of absolute and relative effect estimates, and determining effect size and certainty of evidence corresponding to effect estimates, represent fundamental evidence-based practice competencies that promote informed clinical decision-making. While research has been conducted in the medical profession, based on our literature review there is no published research on these competencies in the nutrition and dietetics profession. METHODS: Among registered dietitians, our main objectives were to assess (1) their understanding and perceived usefulness of three absolute and two relative effect estimate approaches to determine effect size, (2) their perceived usefulness of certainty of evidence, and (3) factors influencing their understanding and perceived usefulness. We conducted a web-based, cross-sectional survey by recruiting dietitians from the Academy of Nutrition and Dietetics (United States). Participants received effect estimates based on hypothetical dietary interventions vs. usual diet for reducing myocardial infarction risk. RESULTS: Of the 11,050 dietitians who received the survey link, 210 participated, and only completers (n&#x2009;=&#x2009;114) were included in our analysis. Participants demonstrated a similar understanding of the relative (27.6%) and absolute (27.5%) effect estimates, with Risk Difference being the best understood approach and Number Needed to Treat being the least (30.7% vs. 24.6% correct responses). While perceived usefulness scores were similar between five approaches, they were highest when data was presented as Relative Risk [mean (SD): 4.82 (1.50)]. Dietitians rated the usefulness of certainty of evidence favorably [mean (SD): 5.07 (1.83), on a 7-point scale], and no factors were associated with correct understanding. CONCLUSION: Dietitians may have limited understanding of effect size thresholds presented in our survey, a finding mostly consistent with surveys of other health professionals. To optimize informed decision-making between dietitians and clients, dietetic programs and continuing education platforms should consider additional training on effect estimate approaches (relative and absolute), and determining effect sizes and certainty of evidence for effect estimates.

Clinical nutrition

Stable chloroform emissions in southeastern China: insights from recent observations.

Chloroform (CHCl3) is a short-lived ozone-depleting substance not currently regulated under the Montreal Protocol. Due to the unique meteorological conditions in East Asia, CHCl3 emitted in this region has a greater potential to reach the stratosphere and contribute to ozone depletion. As an essential component of national CHCl3 emissions, southeastern China has attracted increasing attention. However, long-term observational data in this region remain relatively scarce, with no updates since 2020. In this study, we continuously measured atmospheric CHCl3 concentrations at a remote monitoring station in southeastern China from 1 June 2023 to 31 May 2025. Frequent concentration enhancements were observed during the monitoring period, with mixing ratios ranging from 9.3 to 134.1 ppt and an average value of 36.8 &#xb1; 19.7 ppt. Back-trajectory analysis indicated that air masses associated with elevated CHCl3 levels primarily originated from coastal industrial provinces in eastern China. Using the Potential Source Contribution Function and Concentration Weighted Trajectory methods, we identified the Yangtze River Delta (Jiangsu, Anhui, and Zhejiang Provinces) and Jiangxi Province as dominant source regions. Emissions of CHCl3 in southeastern China were estimated using the Tracer Ratio Method to be approximately 30.1 &#xb1; 5.3 Gg/yr from 2023-06-01 to 2025-05-31, indicating overall stability relative to earlier estimates and no apparent upward trend. These findings provide updated insights into the current status of CHCl3 emissions in southeastern China and highlight the need for continued monitoring and emission assessment of CHCl3 in East Asia, given its unregulated status and implications for ozone layer recovery.

Air Pollutants

Global molecular and serological evidence of dengue and chikungunya infection: a systematic review and meta-analysis of 158,608 tested participants.

INTRODUCTION: Dengue virus (DENV) and chikungunya virus (CHIKV) are Aedes-borne arboviruses with overlapping clinical manifestations, shared vectors, and substantial diagnostic challenges in co-endemic settings. This systematic review and meta-analysis synthesized published evidence on molecular detection, serological positivity, and DENV-CHIKV dual positivity/co-infection in human clinical, surveillance, and community-based study populations. CONTENT: Following PRISMA 2020 guidance, five bibliographic databases (PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar) and supplementary grey-literature/preprint sources were searched for English-language studies published from 1 January 1980 to 31 December 2024. No prospective PROSPERO or OSF protocol registration was available. Eligible records reported extractable numerators and denominators for DENV and/or CHIKV in humans using recognized molecular or serological assays. A total of 196 studies comprising 158,608 tested or suspected participants were included in the extraction table. The pooled CHIKV estimate was 14.0&#x202f;% (95&#x202f;% CI: 12.0-16.4; I2=97.5&#x202f;%), with molecular and serological estimates of 9.8 and 15.7&#x202f;%, respectively. The pooled DENV estimate was 13.8&#x202f;% (95&#x202f;% CI: 10.9-17.3; I2=99.0&#x202f;%), with molecular and serological estimates of 13.1&#x202f;% (95&#x202f;% CI: 7.9-21.0) and 14.3&#x202f;% (95&#x202f;% CI: 10.2-19.8), respectively. DENV-CHIKV dual positivity/co-infection was 52.9&#x202f;% (95&#x202f;% CI: 48.7-57.1) among studies that tested and reported both outcomes. Country-level estimates varied widely and should be interpreted as summaries of available studies rather than nationally representative burden estimates. Funnel-plot asymmetry was statistically significant in DENV analyses but not in the overall CHIKV analysis. SUMMARY: Available evidence indicates extensive but highly heterogeneous DENV and CHIKV positivity across selected clinical and surveillance populations. The pooled estimates should be interpreted cautiously because of substantial between-study heterogeneity, diagnostic variability, outbreak-period sampling, and uneven geographic representation. OUTLOOK: The findings support integrated arboviral surveillance, multiplex diagnostics, and vector-control preparedness in co-endemic regions.

Humans

Analgesic effect of premixed nitrous oxide in postoperative rehabilitation for ankle fractures: a randomized controlled trial.

INTRODUCTION: The global incidence of ankle fractures is on the rise, effective postoperative rehabilitation is a crucial aspect of surgical management. However, the occurrence of severe pain during the rehabilitation continues to pose a substantial clinical challenge. METHODS: The study utilizes a dual-arm, single-center, double-blind, randomized controlled trial design. A total of 100 participants were enrolled. Participants included patients experiencing acute pain (self-reported pain score &#x2265;4) who underwent postoperative rehabilitation for ankle fractures. Participants undergoing rehabilitation training were randomized to receive either 65% nitrous oxide or 100% oxygen. The primary outcome measured was the pain score, while secondary outcomes encompassed anxiety scores, physiological indices, side effects, patient and therapist satisfaction, acceptance, and residual pain. RESULTS: Pain scores were found to be significantly lower in the nitrous oxide group than in the oxygen group (T1: median difference -3.0, [95% CI -3.4 to -2.6]; p&#x2009;<&#x2009;0.001; T2: median difference -2.0, [95% CI -2.8 to -1.2]; p&#x2009;<&#x2009;0.001). Compared with the oxygen group, both therapists (p&#x2009;<&#x2009;0.001) and participants (p&#x2009;<&#x2009;0.001) in the nitrous oxide group reported significantly higher satisfaction levels. Acceptance rate showed significant intergroup differences (p&#x2009;<&#x2009;0.001). No severe adverse effects were observed in either group. Anxiety scores between the two groups did not show a significant difference (p&#x2009;=&#x2009;0.31, &#x3b7;2 = 0.027). CONCLUSION: The safety and analgesic profile of nitrous oxide renders it a suitable option for pain management in postoperative ankle fractures rehabilitation, thus providing a safe and easily manageable alternative to the current available strategies. CLINICAL TRIAL REGISTRATION: We have registered at https://www.chictr.org.cn and the registration number is: ChiCTR2400089379.

Humans

Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.

Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a systematic review of human studies examining manic or hypomanic symptoms following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA (CRD420251160656). Databases and trial registries were searched through January 26, 2026. Eligible designs included randomized and non-randomized clinical studies, registry-based cohorts, cross-sectional surveys, and longitudinal observational studies. Outcomes included dysphoria/euphoria, manic or hypomanic symptoms and transition to bipolar disorder. Risk of bias was assessed using ROBINS-I, ROB2 or NIH tools. Twenty-three studies met inclusion criteria, four contributing to meta-analysis. Rates of psychedelic-associated dysphoria/euphoria, hypomania or mania ranged from 5.8% in controlled trials of psilocybin-assisted psychotherapy for major depressive disorders to 30% in naturalistic studies of individuals with bipolar disorder. When present, manic symptoms were typically acute and self-limited. Observational studies identified higher risks among individuals with bipolar I disorder, familial vulnerability, polysubstance use, and unsupervised or illegal use. Registry-based cohorts examining diagnostic transitions showed a prevalence of subsequent transition to bipolar disorder of 4% (95% CI 2-8%; N&#x2009;=&#x2009;7478; I&#xb2;&#x2009;=&#x2009;32.1%), with little evidence for a hallucinogen-specific signal. Overall, serotonergic psychedelics appear to pose a low but clinically meaningful relative risk of transient mood-related symptoms in susceptible individuals while remaining relatively safe in controlled clinical settings. Long-term outcomes and repeated exposure remain insufficiently studied, underscoring the need for rigorous longitudinal research.

Humans

Prevalence of Breastfeeding in Infants With Down Syndrome: A Systematic Review and Meta-Analysis.

AIM: To estimate the prevalence of breastfeeding-overall, exclusive, partial and depending on infants' age-in infants with Down syndrome, and to investigate associated factors. METHODS: A systematic literature search was conducted in Medline, Cochrane Library, Web of Science, Embase, CINAHL and SciELO up to 1 August 2024. Original articles that estimated the prevalence of breastfeeding in infants with Down syndrome, written in French, English or Spanish, were included. Study quality was assessed using the Joanna Briggs Institute (JBI) scale. Meta-analyses were performed for breastfeeding outcomes and meta-regression explored heterogeneity. The review was registered in PROSPERO (CRD42021278019). RESULTS: Twenty-six studies (3463 infants) were included. The estimated prevalence of overall breastfeeding regardless of duration was 71.6% (95% CI [60.3; 80.7]; 25 studies, 3351 infants) with high heterogeneity, I2&#x2009;=&#x2009;94%. The estimated prevalence of exclusive breastfeeding was 38.4% (95% CI [22.4; 57.3]; 10 studies, 1099 infants). No factor assessed in meta-regression was significantly associated with overall breastfeeding. CONCLUSION: The estimated breastfeeding prevalence in infants with Down syndrome is similar to that reported in the general population, despite high heterogeneity. Further studies using standardised methodology to assess breastfeeding barriers and facilitators in the context of Down syndrome would allow us to improve support for breastfeeding.

Humans

From buffalo to human: Klebsiella pneumoniae in high-somatic cell count milk as an overlooked link in the one health chain.

High somatic cell count (SCC) is a critical indicator of udder health and milk quality in buffalo milk production. However, in many low-income regions, SCC monitoring is often underemphasized, allowing a proportion of high-SCC buffalo milk to enter the food chain and potentially compromising food safety and public health. Klebsiella pneumoniae (K. pneumoniae) is a common zoonotic pathogen found in high-SCC milk, yet systematic investigations into the prevalence and characteristics in high-SCC buffalo milk remain limited. In this study, 23 K. pneumoniae strains were screened out from 460 bacterial isolates obtained from high-SCC buffalo milk samples from Guangxi, China, with an isolation rate of 5.0%. These isolates were comprehensively characterized using whole-genome sequencing and comparative genomic analyses. The results revealed that 78.26% (18/23) of the isolates shared high genomic similarity with the human reference strain ATCC 13883, and the ST37 clone exhibited a pronounced potential of cross-species transmission. All isolates harbored core adhesion factors and intrinsic resistance genes. Notably, several strains displayed high-risk features: strain 419 carried the K1 capsular serotype, strain 326 possessed a complete yersiniabactin synthesis gene cluster, and strain 320 exhibited a multidrug-resistant phenotype. Phenotypic assays further demonstrated a positive correlation between biofilm formation capacity and virulence in Galleria mellonella. Metabolic pathway enrichment analyses suggested that K. pneumoniae has undergone substantial adaptation to the nutrient-rich buffalo milk environment. Collectively, these findings confirm that raw high-SCC buffalo milk serves as a significant reservoir for high-risk zoonotic K. pneumoniae. While industrial thermal processing effectively eliminates viable pathogens, the resilient antimicrobial resistance determinants within these isolates pose a persistent risk of horizontal gene dissemination along the food chain, providing critical evidence for enhancing pre-processing milk quality regulations within a One Health framework.

Animals

Association of Baloxavir Treatment Timing with Serial Interval and Household Transmission of Influenza through a Likelihood-Based Analysis.

BACKGROUND: Baloxavir treatment is associated with reduced influenza transmission within households, and the serial interval varies by treatment status. However, it remains unclear how baloxavir-induced changes in the serial interval relate to household transmission. We aimed to quantify the model-based association between baloxavir treatment timing and the serial interval and household transmission risk. METHODS: We conducted a household survey of influenza cases in Japan between October 2018 and February 2019. We defined the likelihood-based model integrating the serial interval distribution by treatment status and the secondary attack rate (SAR) using individual-level data from index cases. Using this model, we estimated the reduction in the serial interval associated with baloxavir treatment. RESULTS: Compared with untreated index cases, baloxavir-treated cases were estimated to have a serial interval density reduced by 21.42% following treatment. Treatment within 24 hours was associated with a 0.1685 reduction in the area under the curve, with smaller reductions as treatment was delayed. Earlier treatment was associated with a shorter, more concentrated distribution, whereas treatment 72 hours after onset resembled untreated cases. CONCLUSIONS: Our findings highlight that baloxavir treatment is associated with a shorter serial interval and lower estimated secondary household transmission risk. We provide model-based estimates suggesting that earlier administration is associated with a greater reduction in serial interval density and estimated transmission risk, which may inform public health strategies for infection control.

Influenza

Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.

Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.

Adverse outcome pathway

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44&#xa0;&#xb0;C) and compared with control conditions (27&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals

Comparison of black carbon measurements using filter-specific reference transmittance to those using lab blanks or an average of unloaded filters.

Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). We analyzed 5,379 15&#x2009;mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial to assess the influence that different methods of I0 estimations have on eBC measures. We compared eBC measurements using filter-specific I0 values (Method 1) to those using three other methods of I0 estimation: the lab blank scan from a given session (Method 2), the average of all pre-sample filter scans (Method 3), and the average of all lab blank filter scans (Method 4). We assessed the agreement between Method 1 and the alternative methods using Bland-Altman analysis. We also assessed the relationship between Method 1 and the alternative methods across the complete measurement range and after stratifying exposure data into quartiles according to Method 1 eBC exposures. The mean (SD) personal eBC exposure for Method 1 was 7.8&#x2009;&#x3bc;g/m3 (5.9), and exposures ranged from 1.3 to 46.8&#x2009;&#x3bc;g/m3. Compared to Method 1, eBC using Methods 2, 3, and 4 were higher by 0.7&#x2009;&#x3bc;g/m3, 0.1&#x2009;&#x3bc;g/m3, and 0.7&#x2009;&#x3bc;g/m3, respectively. The performances of linear regression models between Method 1 and all other methods were moderate to strong (R2 range: 0.42-0.93) in the second, third, and fourth quartiles; however, the models in the first quartile (eBC range: 1.3-2.9&#x2009;&#x3bc;g/m3) performed poorly (R2&#x2009;=&#x2009;0.25-0.26), with error approximately 25% of the mean. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.Implications: Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). To assess the influence that different methods of I0 estimations have on eBC measures, we analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.

Soot

Epidemiological status of bovine viral diarrhea virus in water buffalo (Bubalus bubalis): A global systematic review and meta-analysis.

Bovine viral diarrhea virus (BVDV) remains a neglected viral disease in water buffalo despite its significant economic impact in production systems. Although limited epidemiological studies have been reported worldwide, the serostatus and active infection in buffalo have not been systematically reviewed. A systematic review and meta-analysis were conducted to estimate BVDV prevalence in water buffalo and identify associated epidemiological factors. Relevant studies published up to January 31, 2026, were retrieved from five electronic databases. A total of 49 studies were identified from 15 different countries were found for inclusion. A random-effects model was used to estimate pooled-prevalence and assess heterogeneity among studies. A meta-analysis of 37 studies (9270 buffalo) estimated a pooled BVDV seroprevalence of 30.5%, while analysis of 16 studies (7189 animals) indicated an antigen prevalence of 16.5%. Continent-wise analysis revealed the highest BVDV seroprevalence in South-America (44.0%), while antigen prevalence was highest in Africa (21.2%) followed by Asia at 12.2%, and no BVDV data reported from North-America. Among the different countries, the highest BVDV seroprevalence was detected in Turkey (61.6%) and Argentina (59.0%), while antigen prevalence was highest in Egypt (21.2%), with lower estimates in Brazil (11.8%) and Iraq (11.3%). Notably, high heterogeneity (I2&#xa0;>&#xa0;90%) was observed in the all-pooled estimates, indicating variations in sampling period, age, sex, sample source and types, diagnostic methods, production-system, and study quality. These findings demonstrate the widespread presence of BVDV in water buffalo populations and indicate the need for targeted control strategies to mitigate its impact on health and productivity.

Animals