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Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans

Coordinated use of three homocysteine methyltransferases supports l-methionine biosynthesis and environmental adaptation among plant-associated bacteria.

Plant pathogens colonize multiple plant-associated habitats throughout their life cycle, encountering distinct nutrient conditions and microbial communities. l-methionine is required for bacterial growth and environmental adaptation. However, how plant pathogens coordinate l-methionine biosynthetic pathways to adapt to different plant-associated environments remains poorly understood. Here, using the plant pathogen Xanthomonas campestris pv. campestris strain XC1 as a model, we show that three homocysteine methyltransferase pathways allow XC1 to catalyze the final step of l-methionine biosynthesis using different methyl donors and cofactors under different environmental conditions. Bioinformatic and transcriptional analyses identified three homocysteine methyltransferase-associated operons in XC1, mesMXD, mmuPM, and metHRHaHb, corresponding to the MesD-, MmuM-, and MetHaHb-dependent pathways, respectively. MesD uses an endogenously synthesized methyl donor and functions as the dominant homocysteine methyltransferase under l-methionine-limiting conditions, supporting bacterial growth, intracellular l-methionine accumulation, and full virulence. Furthermore, MmuM enables XC1 to use plant-derived S-methylmethionine for l-methionine biosynthesis, whereas MetHaHb enables XC1 to use vitamin B12 supplied by a neighboring bacterium for l-methionine biosynthesis in co-culture. Expression analyses showed that mesMXD was the only homocysteine methyltransferase-associated operon that responded to l-methionine availability, and its expression also decreased when S-methylmethionine- or vitamin B12-dependent pathways supported l-methionine biosynthesis. Comparative genomic analysis further showed that the three-homocysteine methyltransferase configuration is conserved in Xanthomonas and is also present in other plant-associated bacteria. Together, these findings show that a plant pathogen can coordinate endogenous, plant-derived, and microbially supported homocysteine methyltransferase pathways to maintain l-methionine biosynthesis, providing a metabolic strategy for adaptation to plant-associated environments.

Methionine

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50&#x2009;mg/day) or placebo for 12&#x2009;weeks. The primary endpoint was point-prevalence abstinence at 12&#x2009;weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3&#x2009;years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12&#x2009;weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p&#x2009;<&#x2009;0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3&#x2009;months (28% vs. 54%, p&#x2009;=&#x2009;0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p&#x2009;=&#x2009;0.07). Maintenance of abstinence at 6&#x2009;months favoured naltrexone (22% vs. 8%, p&#x2009;=&#x2009;0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5&#xd7; ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63&#x2009;&#xb1;&#x2009;1.16 vs. 9.29&#x2009;&#xb1;&#x2009;1.78, p&#x2009;<&#x2009;0.01) and OCDS-C score (6.35&#x2009;&#xb1;&#x2009;1.23 vs. 9.02&#x2009;&#xb1;&#x2009;1.86, p&#x2009;<&#x2009;0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans

Alcohol use disorder and childhood adversity in the association between polygenic risk and suicidality.

OBJECTIVE: Suicidal ideation (SI) and suicide attempt (SA) are both influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate the effects of genetic liability for suicidality. METHODS: Using data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime suicidality outcomes. We evaluated whether AUD partially accounted for these associations and ACEs moderated the direct and indirect associations. RESULTS: The SA PGS was significantly associated with SA (AFR: b&#xa0;=&#xa0;0.36, SE&#xa0;=&#xa0;0.01; EUR: b&#xa0;=&#xa0;0.17, SE&#xa0;=&#xa0;0.01; both ps&#xa0;<&#xa0;2e-16), but the SI PGS was not associated with SI (p&#xa0;>&#xa0;0.55). AUD statistically mediated the association between the SA PGS and SA, accounting for approximately 2% of the total association in AFR individuals and 10% in EUR individuals (both ps&#xa0;<&#xa0;2e-16). Notably, the proportion of the association that was accounted for by AUD decreased as ACEs exposure increased, from 4.30% to 0.54% in AFR individuals and from 13.31% to 3.44% in EUR individuals. In contrast, there was only very modest mediation and no moderated mediation for SI. CONCLUSIONS: Particularly among individuals with lower ACEs exposure, AUD accounted for a meaningful proportion of the association between genetic liability to SA and lifetime SA. These findings highlight different correlates across suicidality phenotypes and suggest potential clinical relevance for AUD in the association between genetic liability and SA.

Adult

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

Determinants of Meal Satisfaction and Their Association With Childhood Obesity: A Systematic Review.

Meal satisfaction is considered a multidimensional concept that includes sensory enjoyment, cognitive, emotional, and physiological components and relates to contentment with the meal experience as a whole. However, its relevance to eating behavior and body weight remains unclear, especially in children. The present review investigated the potential relationship between meal satisfaction-related constructs and childhood obesity, and whether this relation is shaped by individual factors and the external environment. Seventeen eligible studies from 350 records published between 2008 and 2024 were included. No study directly assessed meal satisfaction; instead, proxy measures were used. Food enjoyment emerged as the proxy most consistently associated with BMI, often clustering with higher food responsiveness, lower satiety responsiveness, and emotional overeating. Parental feeding practices, especially pressure to eat, significantly contributed to variation in children's eating behavior and were associated with lower food enjoyment. Overall, meal satisfaction could be a key aspect to consider in childhood obesity prevention programs. However, to date, the available evidence is heterogeneous and predominantly observational. Future longitudinal and intervention studies are needed, alongside child-appropriate instruments to objectively quantify food satisfaction in children. Research that helps understand the role of contextual eating factors on children's meal satisfaction and eating behavior is also warranted.

Humans

The Dual Role of Executive Functioning in the Association Between Family Socioeconomic Status and Children's Problem Behaviors.

Although prior research suggests that executive functioning may either mediate or moderate the association between family socioeconomic status (SES) and children's problem behaviors, examining these roles separately provides an incomplete account: mediation models may understate individual differences that are not attributable to the environment, whereas moderation models may understate the role of the environment in shaping personal characteristics. To integrate these perspectives, the present longitudinal study examined whether executive functioning simultaneously mediates and moderates the association between family SES and children's internalizing and externalizing problems. A total of 308 children in the early years of elementary school (MageT1 = 7.34 years; 138 girls) were assessed and followed up 39 months later. After controlling for children's gender, age, and grade, lower family SES at T1 significantly predicted higher levels of both internalizing and externalizing problems at T2. Executive functioning at T1 partially mediated these associations, indicating that differences in children's executive functioning partly accounted for socioeconomic disparities in problem behaviors. Executive functioning also moderated both associations: SES was negatively associated with problem behaviors among children with lower executive functioning but not among those with higher executive functioning. These findings highlight the dual role of executive functioning in the longitudinal association between SES and children's problem behaviors and suggest that executive functioning may be a promising target for efforts to reduce mental health disparities associated with socioeconomic disadvantage.

Humans

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals

The Association Between Child Maltreatment and Quality of Life: A Systematic Review and Meta-Analysis.

The association between child maltreatment (CM) and quality of life (QoL) has been widely examined in the past decade. In this study, we estimated the association between CM and QoL using a systematic review and meta-analysis. Articles were searched up to May 15, 2024, in both English databases (Web of Science, EMBASE, CINAHL, PsycINFO & PsycArticles, MEDLINE, Cochrane Library, PubMed, and Scopus) and Chinese databases (CNKI, Weipu, and Wanfang). The meta-analysis was performed by a random-effects model, using 43 studies comprising 130,884 participants. This study demonstrated that general CM had an adverse impact on QoL and its sub-dimensions, including physical, mental, psychosocial, and environmental QoL. Further analysis showed that the subtypes of CM also had negative impacts on the dimensions of QoL, except for mental QoL. Emotional maltreatment had stronger negative associations with QoL than other subtypes of CM, while neglect received relatively less attention. In addition, the association between CM and QoL was moderated by region, gender ratio, and measurement methods. The findings of this study suggest that CM is negatively associated with QoL. Future studies need to investigate the impact of neglect on QoL and develop tailored programs to improve the QoL of people who have suffered from CM.

Humans

Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017-2020 Study.

BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been regarded as a disease closely related to obesity, its prevalence is gradually rising in nonobese populations. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel metabolic biomarker that has been shown to be associated with MASLD. However, its role in nonobese individuals remains unclear. This study aimed to investigate the association between UHR and nonobese MASLD. METHODS: Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. UHR was calculated as the serum uric acid (UA) divided by the high-density lipoprotein cholesterol (HDL). Liver steatosis (using controlled attenuation parameters, CAP) and fibrosis (using liver stiffness measurement, LSM) were evaluated through vibration-controlled transient elastography (VCTE). Multivariate linear regression was employed to evaluate associations. Nonlinear relationships were examined using smoothed curve fitting. RESULTS: This analysis included 3573 participants (47.41% male; aged 20-80 years). Log2-UHR was positively associated with CAP (&#x3b2; = 9.96, 95% CI: 6.93-12.98, P < 0.001) and MASLD prevalence (OR = 1.64, 95% CI: 1.38-1.95, P < 0.001). Subgroup analyses revealed significant interactions by sex, age, ethnicity, and smoking status (all P for interaction < 0.05), with stronger associations in females, adults aged 40-59 years, individuals of other Hispanic ethnicity, and never-smokers. Moreover, the association between log2-UHR and CAP was linear and positive (P < 0.01). No significant association was found between log2-UHR and LSM (P > 0.05). CONCLUSIONS: UHR is independently associated with hepatic steatosis but not fibrosis in nonobese US adults, suggesting its potential utility as an early risk assessment to tool. Large scale prospective studies are needed in the future to further validate the conclusions of this study.

Humans

Protective association of the ELMO1 rs741301 variant against diabetes mellitus and diabetic nephropathy: a systematic meta-analysis of case-control studies.

CONTEXT: Diabetes mellitus (DM), an endocrine disorder, is characterised by persistently elevated blood glucose levels due to inadequate insulin production. Diabetic nephropathy (DN), is a critical complication associated with DM, often leading to end-stage renal failure and increased mortality. OBJECTIVE: This meta-analysis aimed to evaluate the association between the ELMO1 rs741301 polymorphism and susceptibility to DN among individuals with diabetes. METHOD: A systematic literature search was conducted for studies published between 2014 and 2024 using Embase, Google Scholar, and PubMed. Eligible case-control studies investigating the association between ELMO1 rs741301 and DN among individuals with DM were selected according to predefined inclusion criteria. Nine case-control studies comprising 880 individuals with DM and 1008 individuals with DN were included in the meta-analysis. RESULTS: The pooled analysis demonstrated a significant protective association between the ELMO1 rs741301 polymorphism and DN under the allelic model (OR = 0.77, 95% CI: 0.67-0.88), recessive model (OR = 0.74, 95% CI: 0.61-0.90), and dominant model (OR = 0.68, 95% CI: 0.53-0.88). In contrast, no statistically significant association was observed under the over-dominant model. CONCLUSION: The findings suggest that the ELMO1 rs741301 polymorphism may be associated with a reduced susceptibility to DN among individuals with DM. These findings provide evidence for a potential genetic contribution of ELMO1 to DN susceptibility and may help improve understanding of the genetic factors underlying diabetic complications. Further well-designed studies in diverse populations are warranted to validate this association.

Humans

Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction-Associated Steatohepatitis-Reanalysis of Fibrosis Stage 2-3 Subset.

BACKGROUND: Resmetirom is an oral thyroid hormone receptor beta agonist clinically used to treat metabolic dysfunction-associated steatohepatitis (MASH) among adults with stage F2 or F3 fibrosis. AIMS: Because the pivotal, 52-week, randomized, controlled, phase 3 MAESTRO-NASH trial (once-daily oral resmetirom 80 or 100&#x2009;mg or placebo) included patients with F1, F2, or F3 fibrosis, we conducted a post hoc analysis aimed at assessing treatment response in the subset of patients with stages F2 and F3 fibrosis, consistent with the approved label population. METHODS: Co-primary end points were MASH resolution (hepatocellular ballooning score 0, lobular inflammation score &#x2264;&#x2009;1, and &#x2265;&#x2009;2-point nonalcoholic fatty liver disease activity score [NAS] reduction from baseline) with no fibrosis worsening, and &#x2265;&#x2009;1-stage fibrosis improvement with no NAS worsening at Week 52. RESULTS: Among 917 patients with F2 or F3 fibrosis, metabolic risk factor prevalence was high (hypertension, 78.0%; dyslipidemia, 71.1%; type 2 diabetes, 67.0%). MASH resolution was achieved by 25.7% in the 80-mg group, 29.9% in the 100-mg group, and 9.5% in the placebo group (p&#x2009;<&#x2009;0.0001 for both comparisons with placebo). Respective percentages with fibrosis improvement were 26.5%, 28.9%, and 17.3% (p&#x2009;<&#x2009;0.01 for both comparisons). From baseline to Week 24, low-density lipoprotein cholesterol decreased by 11.7% and 13.7% in the 80- and 100-mg resmetirom groups, respectively, and increased by 2.3% with placebo (p&#x2009;<&#x2009;0.0001 for both comparisons). No new safety signals emerged. CONCLUSION: Results among patients with F2 and F3 fibrosis were consistent with the primary MAESTRO-NASH analysis population, demonstrating efficacy and safety of resmetirom after 52&#x2009;weeks.

Humans

Associations Between Paternal Pre-Conceptional Body Mass Index and Lifestyle Factors and Offspring Weight Development.

BACKGROUND: Evidence suggests that pre-conceptional paternal factors, including BMI and diet, may influence offspring development. OBJECTIVES: We examined the associations between paternal BMI, dietary protein intake, glycemic index (GI), smoking and alcohol consumption and offspring development during the first 5&#x2009;years of life. METHODS: This secondary analysis of an RCT included 162 father-child pairs from pregnancies among women with pre-pregnancy overweight or obesity. Paternal characteristics were reported at gestational week 15, reflecting the preceding 3&#x2009;months. Offspring anthropometry was measured at birth, 6 and 18&#x2009;months, 3 and 5&#x2009;years. Associations were examined using linear mixed models and linear regression models. RESULTS: No consistent associations were found between paternal characteristics and offspring outcomes from birth to 3&#x2009;years. At age 5, higher paternal BMI was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.07 (CI: 0.03; 0.10)), fat mass index (&#x3b2;&#x2009;=&#x2009;0.07&#x2009;kg/m2 (CI: 0.02; 0.12)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.05&#x2009;kg/m2 (CI: 0.01; 0.08)). Lower paternal protein intake was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.54 (CI: 0.07; 1.01)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.60&#x2009;kg/m2 (CI: 0.13; 1.07)), while moderately higher protein intake was associated with higher waist-to-height ratio (&#x3b2;&#x2009;=&#x2009;0.03 (CI: 3.00&#x2009;&#xd7;&#x2009;10-3; 0.05)). Higher paternal GI was associated with lower offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;-0.04 (CI: -0.08; -2.14-10-3)) at age 5. Smoking and alcohol were not associated with offspring outcomes. CONCLUSION: Paternal BMI was associated with offspring outcomes at age 5&#x2009;years, while findings for paternal dietary factors were less consistent.

Humans

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals

Global prevalence and associated factors of turnover intention among intensive care nurses: A systematic review and meta-analysis.

OBJECTIVES: To estimate the global prevalence of two distinct turnover intentions among intensive care unit (ICU) nurses-intention to leave the ICU and intention to leave the nursing profession-identify significant sources of heterogeneity, and synthesise associated psychosocial factors. METHODS: Ten databases were systematically searched from inception to September 28, 2025. Two reviewers independently conducted study selection, data extraction, and quality appraisal using Joanna Briggs Institute checklists. Random-effects meta-analyses were performed to estimate pooled prevalence and associated factors. Subgroup and meta-regression analyses explored potential sources of heterogeneity. Associated factors were pooled as odds ratios (ORs) and interpreted within an integrated Job Demands-Resources and Theory of Planned Behavior framework. RESULTS: Forty-six studies published between 2007 and 2025, involving 39,246 ICU nurses, were included. The pooled prevalence was 30.7% for intention to leave the ICU and 27.5% for intention to leave the nursing profession. Significant sources of heterogeneity included ICU type, geographic region, publication year, study design, measurement tool, and sampling method. Depression, burnout, high workload, and unsafe patient-to-nurse ratios were associated with increased turnover intention, whereas positive work environments, perceived organisational support, and nursing competence were protective factors. No significant publication bias was detected. CONCLUSIONS: Turnover intention affects approximately one-third of ICU nurses globally and varies across clinical and geographical contexts. Excessive workload, inadequate organisational support, and unfavourable work environments appear to be important contributors to turnover intention among ICU nurses. IMPLICATIONS FOR CLINICAL PRACTICE: Strategies to reduce turnover intention among ICU nurses should focus on reducing excessive workload, improving staffing conditions, strengthening organisational support, and fostering positive work environments. Promoting supportive and sustainable ICU work environments may help improve nurse retention and maintain the quality of critical care services.

Humans

Metatranscriptomic analysis of viral sequences associated with Culex nigripalpus at an Alabama aquaculture site.

Mosquitoes associated with aquaculture habitats can harbor diverse viruses, yet the viromes of many locally abundant species remain poorly characterized. At an aquaculture-associated site in Auburn, Alabama, we surveyed mosquito populations and found Culex nigripalpus to be the dominant species collected. To characterize viruses associated with this mosquito, we performed RNA-seq on pooled female Cx. nigripalpus and compared complementary bioinformatic workflows for viral detection and genome recovery. One workflow removed host-associated reads by mapping to the closest available mosquito reference genome prior to assembly, whereas a second workflow used fully de novo assembly and viral database annotation. Additional protein-level filtering, cross-workflow comparison, and comparison of Trinity and rnaSPAdes assemblies were used to prioritize well-supported viral candidates. Across the original analyses, 16 submitted accessions corresponding to 12 collapsed virus/name groups were recovered, including Merida virus, Hubei mosquito virus 5, Zhejiang mosquito virus, Hubei virga-like virus 3, Rinkaby virus, Elemess virus, Qingnian mosquito virus, Serbia narna-like virus 2, XiangYun narna-levi-like virus 8, Ecclesville picorna-like virus, and baculovirus-like fragments. Several candidates were supported across multiple workflows, while others were recovered only under specific analytical conditions, indicating that candidate recovery was influenced by assembly and filtering choices. Selected viral contigs were independently supported by RT-PCR amplification. Overall, these results provide a first characterization of viral sequences associated with Cx. nigripalpus from an Alabama aquaculture-associated site and show that comparison across assembly and filtering strategies helped prioritize the most consistently supported viral candidates.

Animals

Genome-wide scans reveal candidate genes associated with wing morph differentiation in Tetrix japonica.

Wing dimorphism is an important dispersal-related trait in insects, but its genomic basis remains poorly understood in pygmy grasshoppers. Here, we integrated genome-wide single-nucleotide polymorphism (SNP) analyses, population structure inference, selection scans, and functional annotation to investigate genomic differentiation between long- and short-winged Tetrix japonica. Principal component analysis (PCA), ADMIXTURE, and phylogenetic analyses revealed weak genome-wide separation between morphs, indicating differentiation on a largely shared genetic background. Genome-wide scans based on the fixation index (FST), nucleotide diversity ratios, and Tajima's D, using 50-kb non-overlapping windows and empirical top-5% outlier thresholds, identified multiple candidate regions across seven chromosomes. The broader long- and short-winged candidate sets spanned 9.35&#xa0;Mb and 9.37&#xa0;Mb and directly overlapped 82 and 77 genes, respectively. Candidate genes were associated with signaling/hormone regulation, membrane transport, metabolism, cytoskeletal organization, extracellular matrix structure, and development. Short-winged candidate genes were significantly enriched for ABC-type transporter activity and ATP hydrolysis activity. Because all individuals originated from a single laboratory-maintained population with weak genome-wide structure, these regions should be regarded as candidate loci from a screening-stage analysis that require validation in independent populations and by functional assays, rather than as confirmed targets of selection.

Animals

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

Humans