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PubMed2026

Structural and tissue-specific organisation of endocrine Fgf19 and Fgf21 signalling in rainbow trout.

Endocrine fibroblast growth factors (FGF19 subfamily) play a key role in regulating metabolic homeostasis in vertebrates. However, their functional diversification in salmonids remains poorly understood. In this study, we conducted an integrative characterisation of Fgf19 and Fgf21 signalling in rainbow trout (Oncorhynchus mykiss) by combining phylogenetic, structural and expression analyses. Phylogenetic analyses revealed the conservation of single fgf19 and fgf21 genes, despite the extensive expansion of receptors post-Ss4R (salmonid-specific fourth-round whole genome duplication). Structural modelling and molecular dynamics simulations demonstrated the stable interactions of both ligands to multiple Fgfr isoforms, with receptor-specific energetic profiles and conserved core interaction residues. Tissue expression profiling revealed clear differences from mammalian models, such as predominant hepatic fgf19 expression and the absence of hepatic fgf21 under basal conditions. In addition, there were complex and tissue-dependent distributions of fgfr and klotho transcripts. These findings support a receptor-driven diversification model of endocrine Fgf signalling in salmonids, suggesting enhanced endocrine plasticity associated with the retention of receptors following post-genomic duplication. Taken together, our findings provide new insights into the structural and regulatory organisation of endocrine Fgf signalling, as well as its potential role in metabolic regulation in rainbow trout.

Animals↗

PubMed2026

Integrated physiological and transcriptomic analyses reveal coordinated gill responses to heat stress in pikeperch (Sander lucioperca).

Climate change-driven warming of aquatic environments has made thermal stress an increasingly important factor influencing fish physiological homeostasis. Given their central roles in respiration and osmoregulation, gills are particularly responsive to variations in ambient temperature. Histological examination, physiological measurements, and transcriptome profiling were integrated to investigate the mechanisms associated with heat stress-induced gill injury in pikeperch (Sander lucioperca). Histological analysis revealed that exposure to 29 °C directly caused structural damage to the gills of pikeperch. Oxidative status was evaluated by measuring malondialdehyde (MDA) levels and the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). MDA accumulation was significantly enhanced under heat stress, while antioxidant enzyme activities (SOD, POD, and CAT) displayed a transient increase followed by a subsequent decline. Transcriptome profiling showed marked enrichment of the protein processing in endoplasmic reticulum pathway after heat stress, suggesting activation of endoplasmic reticulum (ER) stress in pikeperch gills. With increasing stress duration, the unfolded protein response (UPR) appeared unable to re-establish ER homeostasis, shifting ire1 and atf6 toward a pro-apoptotic state. Protein-protein interaction (PPI) analysis further highlighted hub genes potentially involved in heat stress-induced ER stress and apoptosis. TUNEL staining and western blotting collectively confirmed that heat stress triggered apoptosis in pikeperch gill tissue. Overall, this study provides new insights into the physiological and molecular responses of pikeperch gills to heat stress and enhances our understanding of thermal stress adaptation in cold-water aquaculture species under climate change.

Animals↗

PubMed2026

Colorimetric gold nanosensors for monitoring protein aggregation: implications for Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It remains a major public health challenge due to the lack of early diagnostic tools and effective disease-modifying therapies. Molecularly, AD is characterized by extracellular amyloid-β (Aβ) plaques and intracellular Tau tangles, as well as soluble oligomers that are likely the neurotoxic species. However, the transient and heterogeneous nature of these oligomers makes them difficult to detect using conventional biosensing approaches. Nanomaterial-based colorimetric biosensors have emerged as promising platforms for detecting protein aggregates and discovering aggregation inhibitors. Specifically, the localized surface plasmon resonance properties of metallic nanomaterials can enable rapid, label-free, and visually detectable colorimetric sensing of molecular interactions. These features can be leveraged to monitor protein aggregation processes in real time and achieve high-throughput screening of aggregation inhibitors, which may collectively enable early detection and timely intervention of AD progression. This Review Article presents the design and engineering of gold-nanomaterial-based colorimetric biosensors for monitoring protein aggregation and highlights the current challenges and emerging opportunities for applying these nanosensors to combat AD.

Journal Article↗

PubMed2026

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p < 0.05). PWV decreased after multiple doses (-0.87 m/s, 95% CI: -1.26 to -0.48 m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (ρ = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans↗

PubMed2026

Plasticity of hepatic metabolism in Arctic char (Salvelinus alpinus) in response to cyclic hypoxia.

The emergence of cyclic hypoxia puts aquatic organisms' homeostasis under significant strain. Energetic metabolism as well as protein synthesis and folding are particularly altered during hypoxia, while reoxygenation imposes an oxidative challenge. Currently, little is known about how hypoxia-sensitive organisms respond to large oxygen fluctuations. Our previous work on Arctic char revealed that this salmonid, despite being strongly affected by acute hypoxia and reoxygenation (H/R), can successfully reestablish homeostasis, notably through adjustments to hepatic mitochondrial metabolism. However, the mechanisms underlying this acclimation remain poorly understood. We hypothesized that Arctic char remodel their hepatic proteome to optimize energy metabolism, reorganize oxygen-demanding pathways, and maintain cellular homeostasis during repeated H/R cycles. By exposing Arctic char to two or fifteen days of diel cyclic hypoxia, we confirmed this species' limited capacity to respond to acute H/R. Nevertheless, after fifteen cycles, fish adjusted their energetic metabolism through coordinated regulation of carbohydrate and lipid pathways and upregulation of amino acid metabolism. Mitochondrial metabolism was strongly reorganized, particularly at the ubiquinone-Complex III interaction level, alongside adjustments in proline utilization and protein processing. Moreover, protein processing and folding pathways were stimulated in both mitochondria and the endoplasmic reticulum. However, chronic cyclic hypoxia may still promote non-mitochondrial ROS production, DNA replication stress, and impaired immune function. This study highlights how a hypoxia-sensitive fish progressively reorganizes its metabolism and oxygen-demanding pathways to establish a phenotype adapted to chronic cyclic hypoxia, while also revealing the physiological costs associated with this acclimation.

Animals↗

PubMed2026

Pesticide occurrence, transformation, and transport from wastewater treatment plants into stream networks with diverse land uses.

Neonicotinoid insecticides and strobilurin fungicides are detected in many environmental compartments and have been associated with negative environmental and human health implications. Wastewater treatment plants (WWTPs) are often hotspots for introducing such contaminants into the environment. Therefore, the occurrence of strobilurin fungicides, neonicotinoids, and their metabolites at two WWTPs with varying land uses and population sizes was investigated. Polar organic chemical integrative samplers were deployed in WWTP influent and effluent and placed upstream and downstream of the effluent mixing zone for 2 weeks in April and July 2022. Biosolids were also collected at each time point. Neonicotinoids were detected with the highest frequency (68%), followed by strobilurin fungicides (49%) and neonicotinoid metabolites (31%). Time-weighted average concentrations for influent/effluent ranged from 85.2 ± 87.8 to 409.4 ± 74.5 ng/L. Pesticide concentrations, specifically the metabolites, typically increased from influent to effluent, resulting in effluent having higher pesticide loads than influent. Pesticide concentrations varied between the upstream and downstream monitoring locations by analyte, with WWTP samples in the highly developed region having significantly higher concentrations of pesticides and less variation by monitoring period. Chronic ecotoxicity benchmarks for freshwater invertebrates for imidacloprid were surpassed in treated effluent at both WWTPs in July and in the downstream monitoring location in the heavily developed area. Findings support the need for further exploration of pesticide contributions from WWTPs to river systems, specifically related to metabolite contributions to downstream streams and their effects on aquatic environments.

Water Pollutants, Chemical↗

PubMed2026

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans↗

PubMed2026

Recent advances in supramolecular macrocycle-based artificial light-harvesting systems.

Artificial light-harvesting systems (ALHSs) inspired by the antenna function of natural photosynthesis provide molecular platforms for collecting excitation energy and directing it to emissive or reactive acceptors. In many supramolecular ALHSs, however, practical performance is limited by poorly defined donor-acceptor orientation, aggregation-caused quenching (ACQ), interfacial defects, and limited stability in aqueous or complex media. Supramolecular macrocycles-particularly pillar[n]arenes (PAs), cucurbit[n]urils (CBs), calixarenes (CAs), cyclodextrins (CDs), and supramolecular coordination complexes (SCCs)-offer a useful design space because their cavities, pre-organized scaffolds, and reversible non-covalent interactions can confine chromophores, tune local donor/acceptor ratios, and modulate Förster resonance energy transfer (FRET). This Review systematically examines the unique structural advantages and assembly mechanisms of the five macrocyclic families, with an emphasis on their use in constructing ALHSs-from single-step to cascaded FRET-and in advancing aqueous photocatalysis, near-infrared bioimaging, panchromatic fluorescence modulation, and singlet oxygen generation. The resulting structure-property-application framework is intended to guide the rational design of macrocycle-assisted photofunctional materials while avoiding overextension of the photosynthesis analogy.

Journal Article↗

PubMed2025

Detoxifying biotransformation of chloramphenicol by Exiguobacterium sp. CAP4 and its bioaugmentation of chloramphenicol biodegradation in simulated wastewater.

The extensive use of chloramphenicol (CAP) in livestock leads the accumulation of CAP in livestock manures, threatening environmental and human health. Therefore, eliminating or reducing CAP concentration in manures before its re-utilization and application through microbial remediation is necessary. Exiguobacterium sp. CAP4, isolated from the plastisphere in duck manures, was capable of degrading CAP with the biodegradation efficiency of 97.8 % at initial CAP concentration of 5 mg/L within 4 days. A total of twenty-four biotransformation products were determined, including two novel transformation products, TP166 and TP203, enriched the integrity of CAP biodegradation pathways. Furthermore, the biotransformation process was proposed as a detoxifying process through biotransformation products toxicity evaluation. Notably, Exiguobacterium sp. CAP4 successfully colonized in the cow manures after inoculation, and bioaugmented the biodegradation of CAP in virgin cow manures. This study significantly extended our understanding of the CAP biotransformation fate, and provided a promising bacterial strain for bioremediation of CAP containing wastewater in situ.

Chloramphenicol↗

PubMed2026

Uncovering molecular regulatory networks of low-temperature stress response in Trachinotus ovatus via integrated transcriptome and metabolome analyses.

Golden pompano (Trachinotus ovatus) is one of the most economically important marine fish species in China. It is susceptible to low-temperature stress, which significantly challenges its production and supply. Nevertheless, study on the regulatory mechanisms underlying low-temperature stress responses in golden pompano remains limited. Here, we firstly performed a time-series transcriptome analysis to reconstruct dynamic response patterns under low-temperature stress in golden pompano. Transcriptome profiling identified common differentially expressed genes (DEGs), including fos, hlf, and hmgb1, as well as condition-specific DEGs across distinct low-temperature stress groups. Based on cluster analysis, all DEGs were classified into five distinct expression patterns, reflecting diversified regulation of expression in golden pompano during low-temperature stress. Furthermore, condition-specific regulatory modules were explored via weighted gene co-expression network analysis (WGCNA), highlighting that the two module hub genes, serbf2 and lipc, might respond to low-temperature stress by regulating the lipid catabolic process. Subsequently, untargeted metabolomic analysis revealed that glycerophospholipid metabolism was a significantly enriched common pathway, highlighting its crucial role in mediating the response to low-temperature stress. Finally, by integrating transcriptomic and metabolomic analyses, a gene-metabolite interaction network associated with glycerophospholipid metabolism under low-temperature stress was established. These findings underscore the significance of multiple candidate genes and glycerophospholipid metabolism in golden pompano's response to low-temperature stress, thereby laying a solid molecular foundation for the development of low-temperature-tolerant fish strains.

Animals↗

PubMed2026

Human iPSC-EV-loaded nanofiber stent coatings accelerate vascular repair by enhancing EGFR/HIF-1α signaling and suppressing ROCK1-mediated remodeling.

Arterial disease management is shifting from antiproliferative drug-eluting stents toward approaches that restore endothelial function and modulate smooth muscle cell (SMC) behavior. Stem cell-derived extracellular vesicles (EVs) carry miRNAs that promote endothelial proliferation and migration while restraining aberrant SMC growth and inflammation. Here, human induced pluripotent stem cell (iPSC)-derived EVs were collected by ultracentrifugation and incorporated into 50:50 poly (lactic-co-glycolic acid) (PLGA 503) core-shell nanofibrous membranes, which were fabricated as stent coatings for sustained release to overcome rapid clearance and poor tissue retention. EVs derived from three independent iPSC lines all enhanced tube formation in human umbilical vein endothelial cells (HUVECs) under hypoxic and serum-starved conditions and revealed a trend toward reduced platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cell (SMC) migration. The fabricated core-shell nanofibers enabled sustained EV release, maintaining therapeutic efficacy for 28 days. Small RNA sequencing (NGS) analysis demonstrated that EVs from these independent iPSC lines shared miR-148a-3p and members of the miR-92 family, which collectively accounted for more than 75% of the reads within the 25 top-expressed miRNA set. In vitro, iPSC-EVs enhanced HUVEC proliferation and survival signaling by downregulating the negative regulators ERRFI1 and VHL, which are specific targets of miR-148a-3p and the miR-92 family, thereby activating the EGFR and HIF-1α axes and driving downstream ERK1/2 and VEGF expression under hypoxic and serum starvation stress conditions. Concurrently, iPSC-EVs prevented PDGF-BB-induced SMC phenotypic switching by downregulating ROCK1, a target of miR-148a-3p, thereby inhibiting downstream AKT and ERK signaling and preserving contractile markers while suppressing the synthetic phenotype. In vivo, the iPSC-EV-functionalized scaffolds significantly accelerated re-endothelialization and inhibited neointimal hyperplasia, evidenced by the upregulation of angiogenic factors (VEGF, CD31) and the concurrent suppression of pathological remodeling markers (α-SMA, MMPs) and inflammatory cytokines (IL-6, TGF-β1). Therefore, iPSC-EVs enriched with specific miRNAs and delivered via PLGA 503 core-shell nanofibers promote endothelial repair while suppressing SMC overgrowth, providing a promising strategy for vascular healing.

Core-shell nanofibers↗

PubMed2026

Robotic Needle Insertion for CT-guided Percutaneous Biopsy of Thoracoabdominal Lesions: A Prospective Multicenter Randomized Trial.

Purpose To compare safety and feasibility between a novel CT-guided robotic system and the conventional freehand technique for puncture biopsy of thoracoabdominal lesions. Materials and Methods In this prospective multicenter randomized trial, individuals with suspected lesions were enrolled between July 2023 and April 2024 across three university teaching hospitals and randomized to the robot-assisted group (n = 82) or the freehand group (n = 83). Procedure outcomes included the technical success rate, targeting error, number of CT scans and needle adjustments, puncture time, and complications. Descriptive and inferential statistics were calculated. Results A total of 165 participants (mean age, 60 years ± 10 [SD]; 83 male) were included. Compared with the freehand group, the robot-assisted group demonstrated a higher technical success rate (97.56% [80 of 82] vs 62.65% [52 of 83], P < .001), lower targeting error (mean Euclidean deviation: 1.7 mm ± 1.1 vs 4.5 mm ± 3.9, P < .001), and fewer CT scans (mean, 4.3 ± 1.9 vs 5.2 ± 2.3; P = .002) and needle adjustments (mean, 0.7 ± 0.7 vs 1.6 ± 1.6; P = .003). Despite differences in geometric precision, both groups achieved 100% (82 of 82 and 83 of 83) diagnostic yield. The median puncture time was comparable between groups (5.5 minutes ± 4.3 vs 4.8 minutes ± 7.0, P = .50). During lung biopsies, the robot-assisted approach yielded fewer complications compared with the freehand approach (4.88% [four of 82] vs 16.87% [14 of 83], P = .014). Conclusion Compared with the freehand approach, robot-assisted biopsy yielded greater precision and reduced adjustments and complications while demonstrating noninferior diagnostic efficacy and comparable duration. Keywords: Robotic Needle Insertion, Biopsy, Thoracoabdominal Lesions, Robot-assisted Biopsy, CT-guided Intervention, Percutaneous Needle Biopsy, Randomized Controlled Trial, Algorithm Development, CT, Clinical Testing, Interventional-Body, Biopsy/Needle Aspiration, Percutaneous, Thorax, Abdomen/GI, Liver, Lung, Kidney ©RSNA, 2026.

Humans↗

PubMed2026

Effect of Various Types of Remineralizing Agents on the Remineralization of Mild and Moderate Defects Caused by Molar-Incisor Hypomineralization in Mexican Schoolchildren: A 12-month Follow-up Randomized Clinical Trial.

PURPOSE: Using Laser-Induced Fluorescence (LIF), this study aimed to evaluate the effect of three remineralizing agents on permanent molars and incisors with both mild and moderate Molar-Incisor Hypomineralization (MIH) in 8-to-12-year-old Mexican schoolchildren. MATERIALS AND METHODS: In this randomized clinical trial, 104 children were selected to participate and then divided randomly into four groups: Group I: control, Oral-B kids (toothpaste); Group II: Fluor Protector (varnish); Group III: Clinpro White Varnish; and Group IV: MI Paste (CCP-ACP). Both varnishes were applied once every four weeks for twelve months for each group. Remineralization was evaluated by LIF at intervals of 1, 3, 6, 9, and 12 months. Paired-sample t-tests and repeated-measures ANOVA were performed, while the Greenhouse-Geisser correction was used to evaluate sphericity. RESULTS: The three test agents used increased the level of remineralization observed at the site of mild and moderate MIH defects over the course of twelve months (p0.001). A similar decrease in average LIF values was observed across the three treatment groups. CONCLUSIONS: The use of both fluoride varnishes and the CPP-ACP toothpaste was observed to promote the remineralization of both mild and moderate MIH defects.

Humans↗

PubMed2025

Tracking microplastic contamination across seasons in a freshwater reservoir: Evidence from surface water, sediments, and fishes.

Microplastics (MPs) are prevalent contaminants in aquatic environments, posing substantial ecological and health risks. These particles migrate within the different layers of aquatic bodies with time and affect the respective biota. Thus, to get an in-depth understanding of the particles, this current study investigated the seasonal distribution, morphological and chemical characteristics, along with potential ecological and human health impacts in the samples including surface water, sediment, and fish from a drinking water supplying reservoir in eastern India. Across three different seasons, pre-monsoon, monsoon, and post-monsoon samples were collected using optimized methods. Results revealed distinct seasonal trends: MP abundance in surface water peaked during the monsoon (mean: 1.15 MPs/L), while sediment showed the highest concentrations in the pre-monsoon (mean: 596 MPs/kg), indicating temporal accumulation dynamics influenced by runoff, hydrodynamics, and sedimentation. Fish gut analysis confirmed ingestion of MPs across five species, with concentrations ranging from 26 to 100 MPs/kg, depending on feeding habits. The most dominant MP type were fragments, followed by fibers, films, and beads. Polymer analysis via µFTIR identified polyethylene, polypropylene, and polyvinyl chloride as prevalent, with hazard assessments (i.e., Polymer Hazard Index (PHI)) indicating medium to very high ecological risks. Heavy metal association was more dominant in the MPs isolated from sediments than the waterborne MPs. Pollution Load Index (PLI) values were > 1 in most seasons, confirming contamination. Health risk analysis suggested potential exposure through both drinking water and fish consumption. This study emphasizes the need for seasonal monitoring, improved waste management, and mitigation strategies to address MP pollution in freshwater ecosystems.

Microplastics↗

PubMed2026

Association between youth athletes' sports specialization and injuries: a systematic review and meta-analysis.

INTRODUCTION: The purpose of this study was to conduct a systematic review and meta-analysis to examine the specialization-injury relationship, and explore whether the specialization-injury relationship is moderated by study design, sport type, age, sex, and injury measurement type, injury mechanism, and anatomical location. METHODS: We searched eight databases by related keywords and assessed the quality of the included studies using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale. The Comprehensive Meta-Analysis (CMA) statistical software 3.7 examined heterogeneity, sensitivity, publication bias, overall effect size of specialization-injury relationship, and moderation effects. This review was prospectively registered in PROSPERO (CRD420251233318). Searches were conducted in eight electronic databases from inception to March, 2026. RESULTS: The 15 included studies showed moderate heterogeneity, stable sensitivity analyses, and no publication bias. The overall odds ratio of the sports specialization-injury relationship was 2.00 (95% confidence interval [1.58-2.55], p < .001). Moderation analyses indicated that sport type significantly influenced the specialization-injury relationship, whereas no significant moderation effects were observed for study design, sex, age, injury measurement type, injury mechanism, and injury anatomical location. CONCLUSIONS: The findings indicate a positive association between sport specialization and injury risk among youth athletes, with variation across sport participation contexts. Specifically, athletes in both contact and non-contact sports demonstrated higher pooled odds of injury than those involved in multiple sports. Although the evidence is heterogeneous and should be interpreted with caution, these findings highlight the potential role of diversified sport participation in relation to injury.

Humans↗

PubMed2026

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE↗

PubMed2026

Vitamin D Deficiency During Pregnancy Is Associated With Greater LDL-C Increase, Elevated β-Hydroxybutyrate and Altered Neonatal Metabolic Markers-A Secondary, Pooled Analysis of the Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

INTRODUCTION: Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS: In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20 weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age > =18 years, singleton pregnancy, < 20 weeks' gestation, BMI ≥ 29 kg/m2. Women with GDM < 20 weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (< 30 nmol/L, n = 102), insufficient (30-50 nmol/L, n = 222) and sufficient (> 50 nmol/L, n = 638) groups. VitD levels and lipid concentrations were assessed at < 20, 24-28 and 35-37 weeks' gestation and in cord blood. RESULTS: Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and ß-OH-butyrate at 24-28 weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher ß-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20 weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION: Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

Humans↗

PubMed2026

Multi-omics insights into the physiological mechanisms of bile acid accumulation in the gallbladder in brumation-like snakes.

Hibernation/brumation represents an important physiological adaptation for animals to cope with seasonal environmental changes. Field observations suggested increased gallbladder weight in the Five-pacer viper (Deinagkistrodon acutus) during brumation, and our quantitative measurements confirmed this increase together with bile acid accumulation. By integrating a multi-omic approach, this study elucidates the regulatory mechanisms of bile acid accumulation in the gallbladder during brumation. Results showed that taurocholic acid (TCA) and taurodeoxycholic acid (TDCA) were the major components in the gallbladder of the brumation-like group, with significantly elevated concentrations of bile acids, whereas bile acid concentrations in serum and intestinal contents were markedly reduced, indicating suppression of the enterohepatic circulation and consequent accumulation of bile acids in the gallbladder. Hepatic transcriptomic analysis revealed significant downregulation of bile acid synthesis and regulatory genes in brumation-like snakes. In contrast, the alternative synthesis pathway gene sterol 27-hydroxylase (CYP27A1) and some transporter genes were slightly upregulated. Further, some modification genes and regulatory genes showed no significant differences between active and brumation-like states. Gut microbiota analysis demonstrated Akkermansia muciniphila, Bacteroides fragilis, and Citrobacter freundii were more enriched in the active group, which were common microbes related to bile acid metabolism, and the correlation analysis confirmed this relationship. Taken together, these findings indicate that the "physiological bile acid accumulation" observed in snakes during brumation-like state is jointly driven by suppressed hepatic synthesis, reduced enterohepatic circulation, and remodeled microbial community structure. The study provides novel comparative physiological insights into extreme metabolic homeostasis in animals.

Animals↗

Results for “chemical and drug&#x2010;induced liver injury”

Results for “chemical and drug‐induced liver injury”