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Acupuncture improves depressive symptoms and prefrontal cortical function in mild to moderate depressive disorder: A randomized sham-controlled trial and fNIRS study.

BACKGROUND: Depressive disorder is a common mental illness associated with substantial functional impairment. Although pharmacotherapy is widely used, its effectiveness is often limited by adverse effects and poor adherence. Acupuncture has been increasingly applied as a complementary treatment for depression, and its neurobiological characteristics remain unclear. OBJECTIVE: This randomized, sham-controlled trial aimed to evaluate the clinical efficacy of acupuncture for mild to moderate depressive disorder and to investigate its effects on prefrontal cortical function using functional near-infrared spectroscopy (fNIRS). METHODS: Patients with mild to moderate depressive disorder were randomly assigned to a real acupuncture (RA) group or a sham acupuncture (SA) group and received standardized treatment for 8 weeks. Clinical outcomes were assessed using the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Short Form-36 Health Survey (SF-36), and a traditional Chinese medicine syndrome score. A subset of participants underwent fNIRS assessment during resting-state and task-based conditions to evaluate prefrontal cortical activation and functional connectivity. RESULTS: Compared with baseline, the RA group showed significant reductions in SDS and SAS scores and significant improvements in SF-36 emotional domains, with effects emerging at Week 4 and persisting up to 12 weeks after treatment. Improvements were greater and more stable in the RA group than in the SA group. fNIRS analyses revealed enhanced activation in dorsolateral and medial prefrontal regions and strengthened prefrontal functional connectivity following acupuncture, whereas neural changes in the SA group were limited. CONCLUSION: Acupuncture is effective for improving depressive and anxiety symptoms and quality of life in patients with mild to moderate depressive disorder. Modulation of prefrontal cortical activation and connectivity may underlie its antidepressant effects.

Humans

Physiological and molecular responses of coelomocytes to low- to mid-frequency acoustic exposure in the sea urchin Strongylocentrotus intermedius.

Underwater noise is a widespread environmental pollutant in marine ecosystems, yet the effects of low- to mid-frequency acoustic exposure on immune physiology and molecular responses in echinoderms remain unclear. In this study, the sea urchin Strongylocentrotus intermedius was exposed to continuous pure-tone acoustic stimulation at 80, 125, 250, 500, 750, and 1000 Hz for 3 h. Results showed that acoustic exposure significantly affected redox homeostasis, energy metabolism, and immune function in S. intermedius coelomocytes: the antioxidant system and glutathione redox balance were altered, as indicated by increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated reduced glutathione (GSH) content, and a higher GSH/GSSG ratio; glycolysis-related enzyme activities were enhanced, with increased pyruvate kinase (PK) activity under 125-500 Hz exposure and elevated hexokinase (HK) activity at 250 Hz; and immune function was impaired, as shown by increased coelomocyte mortality, reduced phagocytic activity, and inhibited acid phosphatase (ACP) and alkaline phosphatase (AKP) activities, whereas respiratory burst activity showed no significant change. Among all treatments, 250 Hz induced the most pronounced physiological responses. Transcriptomic analysis of coelomocytes from the 250 Hz group identified 663 differentially expressed genes, including 537 upregulated and 126 downregulated genes, mainly enriched in pathways related to apoptosis, phagosome, lysosome, glutathione metabolism, arachidonic acid metabolism, and carbohydrate metabolism. These findings indicate that low- to mid-frequency acoustic exposure can act as a physiological and molecular stressor to S. intermedius coelomocytes by affecting redox homeostasis, enhancing energy metabolism, and suppressing immune effector processes, with 250 Hz showing the strongest effect under the present exposure conditions. This study provides experimental evidence for evaluating the potential biological effects of low- to mid-frequency acoustic exposure on benthic echinoderms.

Animals

Understanding Dynamics: A Systematic Review of the Attitudes, Knowledge, and Competencies of European Frontline Professionals Toward Domestic Abuse.

There remains a paucity of European research on attitudes and responses to domestic abuse from frontline workers and professionals who regularly encounter domestic abuse or engage with domestic abuse legislation. This systematic review synthesized qualitative, quantitative, and mixed-method peer-reviewed studies that explored professionals' knowledge, attitudes, and competencies related to domestic abuse. The professionals included medical staff (doctors, nurses, midwives), social care professionals, police officers, and criminal justice practitioners. The review was conducted on current European studies published between 2014 and 2025 and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases consulted included APA PsycInfo, Scopus, Web of Science, PubMed, Sociological Abstracts, International Bibliography of the Social Sciences, Social Services Abstracts, and Google Scholar. Full-text review was performed on 273 articles, of which 36 were deemed appropriate for inclusion. The review included 8 multi-country studies spanning the United Kingdom (England, Scotland, and Wales), and 28 single-country studies conducted in England, Sweden, Turkey, Portugal, the Republic of Ireland, Wales, Bosnia, Spain, Italy, Slovenia, and Hungary. A narrative and thematic synthesis categorized professional attitudes toward domestic abuse into four emergent themes: attitudes toward engagement and responsibility, attitudes toward victims, knowledge and understanding of domestic abuse, and attitudes as predictors of professional practice. This review addresses a dearth of research and provides recommendations for promoting proactive practice among professionals most likely to receive disclosures of abuse.

Humans

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50 mg/day) or metformin (1000 mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL∶HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD = 0.61 (0.02 to 1.21), p = 0.04; metformin: MD = 0.45 (0.07 to 0.83), p = 0.02], with no significant between-group difference in unadjusted analysis (p = 0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (β = -0.324, p = 0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (β = -1.209, p = 0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Humans

Maternal disease control and pregnancy outcomes with anti-CD20 therapy versus natalizumab in multiple sclerosis: a systematic review.

BACKGROUND: Management of multiple sclerosis (MS) during pregnancy requires balancing maternal disease control with fetal safety. Among high-efficacy disease-modifying therapies, anti-CD20 monoclonal antibodies and natalizumab are commonly used in women with active disease, yet their comparative effectiveness and safety during pregnancy remain incompletely defined. This systematic review evaluated maternal disease activity and pregnancy-related outcomes associated with anti-CD20 exposure compared with natalizumab in pregnant women with MS. METHODS: PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched from inception through February 2026. Eligible studies included pregnant women with MS exposed to anti-CD20 before or during pregnancy and reporting maternal disease activity compared to natalizumab. RESULTS: Seven studies were included, comprising six observational cohort studies and one pharmacovigilance disproportionality analysis. Across studies, anti-CD20 exposure was consistently associated with lower relapse activity than natalizumab, particularly in the postpartum period. Anti-CD20 strategies were also associated with markedly lower postpartum MRI activity and more favorable disability-related outcomes where reported. Meta-analysis of three studies demonstrated a significant reduction in postpartum MRI activity with anti-CD20 therapy compared with natalizumab (RR 0.06, 95% CI 0.02-0.24; I² = 0%). No clear increase in major congenital anomalies was identified, although some data suggested higher odds of small for gestational age and maternal antibiotic use with anti-CD20 exposure. CONCLUSIONS: Anti-CD20 therapy was associated with lower maternal disease activity than natalizumab during pregnancy, especially for relapse prevention and postpartum MRI suppression. However, evidence regarding fetal and neonatal safety remains limited, warranting cautious individualized treatment decisions and further comparative research.

Humans

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially &#x3b2;-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating &#x3b2;-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group &#xd7; Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans

Differences in Radiological Risk Perceptions Following Online and In-Person Workshops.

Nuclear energy is widely regarded as a critical part of the pathway toward a secure, low-carbon electricity grid, yet long-term management of used nuclear fuel remains a persistent challenge. Although technically viable options for interim and consolidated storage exist, public concern and community opposition - rooted in historical distrust and risk perception - continue to complicate siting decisions. In response, recent federal efforts have emphasized collaboration-based approaches and community engagement, though empirical evidence on the effectiveness of different engagement strategies remains limited. This study examines how the structure and delivery of community engagement influence changes in public attitudes toward hosting interim used nuclear fuel storage facilities. Using survey data from 13 educational workshops around the United States, we evaluate: (1) the inclusion of trust-building content prior to technical content, and (2) engagement format, comparing online and in-person workshops. Analyses focus on participant changes in perceptions of safety, risk, and support for hosting, using the Wilcoxon rank-sum test and other non-parametric hypothesis tests on surveys conducted before and after workshops. Results indicate that workshop participation is associated with some measurable attitude changes, with significant (p < 0.05) differences in response variability for some questions across workshop formats. In particular, when comparing nuclear energy to other clean energy sources, in-person workshop participants are substantially more likely to gain a more favorable opinion of nuclear energy than online participants. These findings contribute empirical evidence on how trust-building and delivery mode shape outcomes in public engagement on complex and contested energy policy issues such as storage of used nuclear fuel.

nuclear fuel cycle

CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.

CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the past decades in diagnostics, therapeutic genome editing, and vaccine development. The article highlights key platforms like DETECTR and SHERLOCK, which enable rapid, sensitive pathogen detection, and explores CRISPR-Cas9 systems in therapeutic strategies for directly targeting viral genomes and combating antimicrobial resistance. It also examines the role of CRISPR-Cas9 in engineering live-attenuated and personalized neoantigen vaccines. Principal findings demonstrate a clear progression from experimental proof-of-concept to preclinical applications primarily in CRISPR-based diagnostics and the engineering of live-attenuated vaccine candidates, whereas translation in CRISPR-based therapeutics and personalized neoantigen vaccines for infectious diseases remains at earlier, more exploratory stages. CRISPR-based diagnostics have progressed further toward clinical evaluation than therapeutics due to delivery and safety constraints, while personalized neoantigen vaccines are included mainly as an emerging, comparative concept for infectious diseases rather than a mature application. This review uniquely integrates CRISPR-based diagnostics, therapeutics, and vaccine development within a single infectious disease framework, critically assesses their current maturity, and systematically highlights technical, regulatory, and ethical barriers alongside realistic future priorities. The review concludes that while CRISPR-Cas holds transformative potential for infectious disease management, significant challenges in delivery efficiency, off-target effects, and ethical regulation must be addressed to ensure safe and equitable clinical translation.

Humans

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense

Effects of adjunctive bifrontal tDCS on depressive symptoms and cognitive performance in major depressive disorder: A randomized, double-blind, sham-controlled crossover pilot study.

BACKGROUND: Evidence for antidepressant effects of transcranial direct current stimulation (tDCS) in major depressive disorder (MDD) is heterogeneous, and cognitive effects remain uncertain. We compared depressive symptoms and DSST performance during active and sham bifrontal tDCS in medicated outpatients with MDD and baseline HAMD-17 &#x2265; 15. METHODS: In this randomized, double-blind, sham-controlled crossover pilot trial, adults with MDD and inadequate response to an adequate antidepressant trial were assigned to active&#x2192;sham or sham&#x2192;active tDCS sequences while continuing antidepressants. Each period comprised 10 sessions over 2 weeks. Active stimulation was delivered at 2 mA for 20 min (anode F3, cathode F4); sham used the same montage with brief ramping only. No washout interval was used. No washout interval was used. The primary outcome was HAMD-17; secondary outcomes were DSST and CGI ratings. RESULTS: Of 38 randomized participants, 32 completed both periods and were analyzed per protocol. HAMD-17 scores were lower during active than sham stimulation (mean difference -3.63, 95% CI -5.86 to -1.40; p = 0.002), but the condition-by-sequence interaction was significant (p = 0.026). No condition effect was observed for DSST (p = 0.261) or CGI-Severity (p = 1.000); CGI-Improvement was strongly sequence-dependent (p < 0.001). In an exploratory first-period analysis, adjusted T1 HAMD-17 scores were lower in the active-first group (adjusted difference -4.90, 95% CI -7.92 to -1.87; p = 0.003). Adverse effects were mild and transient. CONCLUSIONS: Active tDCS was associated with lower HAMD-17 scores, but the pooled contrast was order-dependent and cannot be interpreted as a definitive treatment effect. No DSST benefit was observed.

Humans

An allograft inflammatory factor enhances sperm viability by modulating intracellular calcium in oyster Crassostrea gigas.

As an important aquaculture bivalve, the Pacific oyster Crassostrea gigas faces severe constraints in artificial reproduction, where low sperm motility often leads to fertilization failure and limits the sustainable development of the oyster aquaculture industry. In the present study, the variation of sperm from different oyster individuals was observed, and high-quality sperm possessed intact, elongated flagella with no structural abnormalities, while low-quality sperm showed shortened flagella with frequent tangling or coiling defects. Transcriptomic analysis comparing high- and low-quality sperm revealed significantly reduced expression of genes associated with sperm motility and release (CgAIF1, CgAchR, CgSEX), sperm quality and development (CgEP4, CgIFi2b), and cryoprotection (CgISPs) in low-quality sperm. Notably, an allograft inflammatory factor (designed as CgAIF1) encoding EF-hand domain, known as Ca2+ binding activity, was among the most significantly downregulated in low-motility sperm. CgAIF1 is highly expressed in haemocytes, ganglia, and gonads of oysters. Incubation with the recombinant AIF1 protein (rCgAIF1) significantly improved sperm curvilinear velocity, thereby enhancing the overall motility of C. gigas sperm. Furthermore, rCgAIF1 incubation increased intracellular Ca2+ levels (2.13-fold at 30&#xa0;min, 2.71-fold at 60&#xa0;min) and superoxide dismutase (SOD) activity (1.44-fold at 30&#xa0;min, 1.24-fold at 60&#xa0;min) in sperm, suggesting potential roles in calcium homeostasis regulation and antioxidant defense. In conclusion, this study demonstrates that CgAIF1 significantly enhances motility of oyster sperm, providing a scientific basis for artificial breeding and seed production in oyster aquaculture.

Animals

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5&#x2009;min). Salivary chromogranin A and &#x3b1;-amylase were measured at baseline and 1&#x2009;min post-task. Only VA% and chromogranin A showed significant condition &#xd7; time interactions (p&#x2009;=&#x2009;0.027-0.039). VA% significantly decreased from before to immediately after the task and 1&#x2009;min post-task in both conditions (p&#x2009;&#x2264;&#x2009;0.002), with significantly higher values in the CP condition than in placebo immediately after and 1&#x2009;min post-task (p&#x2009;&#x2264;&#x2009;0.037). Chromogranin A significantly increased from baseline to 1&#x2009;min post-task in the placebo condition (p&#x2009;<&#x2009;0.001) but not in the CP condition (p&#x2009;=&#x2009;0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant

Evolution of maize recombination landscape during domestication.

Despite the plethora of knowledge about the benefits of meiotic recombination and numerous theoretical studies examining how recombination rates evolve, there is a general lack of empirical support and consensus across species. To fill this knowledge gap, we characterized the evolution of recombination landscape in maize during its domestication from teosinte and related the observed changes to established theoretical frameworks. Through examining recombination in experimental populations of maize and teosinte and the population genomics approach of identifying historical recombination events using ancestral recombination graph inference to generate saturated maize and teosinte recombination maps, we found that during domestication, maize experienced a 12% increase in its genome-wide recombination rate. Furthermore, maize evolved higher recombination rates on the long arms of chromosomes in regions closer to centromeres, where recombination is generally very low. The repatterning of crossover events came from changes in global crossover positioning rather than alterations in cis-acting chromatin factors. Consequently, we found evidence of selection acting on trans-acting recombination modifiers affecting crossover interference and controlling the interference-dependent class I crossover pathway. We show that CO repatterning was likely beneficial for maize fitness, as significant recombination rate increases were predominantly in gene-rich regions, which harbor domestication-related variation. This work suggests genomic and mechanistic processes leading to the evolution of meiotic recombination landscape in response to directional selection pressure and provides evidence for the evolutionary advantage of recombination.

Zea mays

A multi-model genome-wide association study identifies genetic variants underlying resistance to Largemouth Bass Ranavirus (LMBV) in Micropterus salmoides.

Largemouth bass (Micropterus salmoides) is an economically important freshwater aquaculture species, yet recurrent outbreaks of Largemouth Bass Ranavirus (LMBV) continue to impair production and cause substantial losses. The genetic basis of host variation in LMBV resistance remains insufficiently characterized. Here, we applied a multi-model genome-wide association study (GWAS) to identify loci associated with resistance following a controlled challenge with the LMBV-23PY strain. Whole-genome resequencing was performed for 146 phenotyped fish, including 72 susceptible and 74 resistant individuals. After stringent quality control, 877,262 high-quality variants were retained and tested using six GWAS models. Across binary survival status and survival time phenotypes, 32 shared suggestive variants were consistently detected across models, representing suggestive loci for LMBV-23PY resistance. Genes within &#xb1;50&#xa0;kb of these loci were annotated, and functional enrichment highlighted immune- and redox-related biological processes. Three prioritized candidates-GSTT3L (glutathione S-transferase theta-3-like), CGRP2 (calcitonin gene-related peptide 2), and NPPC (natriuretic peptide C)-were associated with pathways involved in oxidative stress responses and immune regulation. Collectively, these results provide insight into the genetic architecture of LMBV-23PY resistance in largemouth bass and identify suggestive variants and associated candidate genes for downstream validation, functional interrogation, and the development of marker-assisted and genome-enabled breeding strategies.

Animals

In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals

Individual differences in brain dynamics across a social cognition network induced by cortico-cerebellar tDCS in adults with autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core diagnostic domains of social communication impairments, restricted interests and repetitive behaviors. Idiosyncratic brain organization is a potential hallmark of ASD. Previous transcranial direct current stimulation (tDCS) studies often targeted dorsolateral prefrontal cortex, with changes oin brain dynamics averaged across the cohort. We utilized a magnetoencephalographic (MEG) array to characterize individual differences in brain dynamics induced by cortico-cerebellar tDCS across nodes of a social cognition network. A randomized, sham-controlled, double-blind, within-subject clinical trial was conducted in a cohort of 24 young adults with ASD or high autistic traits. Two separate sessions of computerized social learning activities were combined with verum/sham tDCS, with anodal electrode over right temporoparietal junction (TPJ) and cathode on right deltoid. Following stimulation, theta- and alpha-band activity were evaluated within nodes of a social cognition network: bilateral TPJ, fusiform, medial prefrontal cortex and Crus I/II of cerebellum. Idiosyncratic participant-specific up- and down-regulation of theta- and alpha-band activity occurred across the network. Activity in right Crus I/II, a region inundated by the stimulation current, strongly correlated with the change of activity summed across all cerebral cortical nodes in theta- but not alpha-band. Intrinsic theta-band activity is believed to mediate input/output relationships in cerebellar cortex and to drive synaptic plasticity. These results suggest that theta-band stimulation of cerebellar cortex might be an effective therapy for individuals on the autism spectrum who present with cerebellar hyperactivity.

Humans

Impact of Physical Environment of Pediatric Inpatient Wards on Children: A Systematic Literature Review.

ObjectiveThe study aimed to examine empirical studies published between 2003 and 2025 to identify elements of physical environments influencing health outcomes and experiences of children and families.BackgroundIn the past 40 years, research has shown that the physical environment influences the health and well-being of patients in the healthcare environment. However, similar research in the context of "pediatric inpatient wards" remains underexplored.MethodsPubMed, Embase, Scopus, and Web of Science were used to identify relevant articles. All extracted articles underwent a three-step screening process using PRISMA. A total of 30 eligible articles were used for the analysis. The protocol is registered at PROSPERO (CRD42023408997).ResultsKey findings reveal positive and negative impacts of identified elements. Positive-effect elements include play spaces, space for parents, natural light, connections with nature, and so on, which promote comfort, healing, and emotional resilience. Conversely, negative-effect elements, such as noise, artificial lighting, uncomfortable temperature, and so on, contribute to stress and disrupted sleep. Mixed effects were observed for elements like art and television, which underscore the complexity of designing environments that address the diverse needs of different age groups and genders.ConclusionsThe review findings highlight significant knowledge gaps. The study also tries to bridge existing gaps between research and practice by systematically identifying environmental elements, offering actionable insights to architects, designers, healthcare providers, and policymakers. Future research must adopt rigorous, culturally inclusive approaches to advance the field of pediatric healthcare design and ensure equitable care across diverse sociocultural contexts.

Humans