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PubMed2026

Domestication-associated reduction of methyl salicylate in tomato root and its significance for resistance to root-knot nematode.

Methyl salicylate (MeSA) plays diverse roles in the aerial parts of plants. By contrast, its biosynthesis and function in roots remain poorly understood. Here, we investigated root MeSA biosynthesis and function in tomato. Genome-wide association studies (GWAS) were performed using root MeSA levels as the phenotype in a diversity panel of 167 accessions to identify associated loci. Candidate genes were biochemically characterized, and the role of MeSA in defense against root-knot nematode (RKN, Meloidogyne incognita) was evaluated using transgenic plants. MeSA was identified as a major root volatile in tomato and showed a domestication-associated reduction. GWAS revealed multiple loci associated with natural variation in root MeSA, including a major locus on Chromosome 9 encoding the salicylic acid methyltransferase (SlSAMT). SlSAMT-overexpressing plants showed reduced resistance to RKNs, whereas SlSAMT-knockdown plants exhibited enhanced resistance. Our results suggest complex roles of MeSA and the salicylic acid (SA) signaling pathway in belowground plant defense. The SA signaling pathway likely plays critical roles in protecting roots against diverse natural enemies, including RKNs. Nevertheless, RKNs appear to have co-opted MeSA as a host-location signal, and the domestication-associated reduction of root MeSA in tomato has likely contributed to enhanced resistance against RKNs.

Solanum lycopersicum↗

PubMed2026

Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.

BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk.

Humans↗

PubMed2026

Algae-to-host horizontal gene transfer in Paramecium bursaria is associated with host adaptation during endosymbiosis.

Paramecium bursaria maintains a stable endosymbiosis with green algae, yet the evolutionary consequences of this association remain unclear. Here, we screened the host genome for algal-derived horizontally transferred genes (HTGs) using a lineage-aware workflow designed to detect horizontal gene transfer (HGT) between two defined lineages. We identified 16 candidate HTGs, including four putative newly transferred genes and 12 homologous transferred genes, most of which were functionally associated with redox homeostasis and metabolism. Five HTGs showed symbiosis-dependent expression. RNAi knockdown of GH32s and SATs reduced host proliferation, total cell area, and motility, while GH32s knockdown also reduced endosymbiont load. Duplication patterns suggest that most transfers may have occurred after the P. bursaria lineage diverged from the sampled Paramecium species but before its lineage-specific whole-genome duplication (WGD). The HTGs also showed host-associated shifts in GC content and gene length, while representative HTGs retained conserved domains and functional motifs. Together, our results support algae-to-host HGT in P. bursaria and suggest that some transferred genes may contribute to metabolic integration during endosymbiosis.

Gene Transfer, Horizontal↗

PubMed2026

A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants.

Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70 mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).

Humans↗

PubMed2026

Genetic mutations driving ciprofloxacin resistance in laboratory-evolved Salmonella Typhimurium.

Ciprofloxacin resistance in Salmonella Typhimurium is a significant public health concern, and the mechanisms by which the resistance evolves are poorly defined. Here, by serial passaging under antibiotic selection, we isolated ciprofloxacin-resistant S. Typhimurium mutants and subjected them to whole-genome sequencing to reveal the major mutations associated with resistance. The Low CipR mutant acquired four chromosomal mutations in ramR, icdA, lipB, and gyrA, and the High CipR mutant gained additional mutations in gyrB, yaiC, and corA. Functional characterization determined that mutations in ramR resulted in efflux pump upregulation, while disruptions in the TCA cycle caused by mutations in icdA and lipB led to metabolic alterations. These changes indirectly enhanced resistance by increasing the expression of the global regulator MarA and reducing OmpF-dependent membrane permeability. Despite the observation of the G105A substitution in GyrA, enzymatic assays confirmed the failure to support resistance to ciprofloxacin, possibly because the structural alteration remained minimal. GyrB488-489dup was associated with maintained supercoiling under ciprofloxacin and enhanced fluoroquinolone resistance, suggesting a major role in resistance evolution. Other mutations in yaiC impaired biofilm and, in corA, intracellular accumulation of magnesium, possibly stabilizing the bacterial cell envelope under antibiotic pressure. The findings provide novel explanations for the multifaceted mechanisms leading to ciprofloxacin resistance in Salmonella and suggest targets to combat antimicrobial resistance.IMPORTANCEAntibiotic resistance in Salmonella Typhimurium is an increasing public health concern, yet the genetic changes that allow bacteria to become resistant are not fully understood. In this study, we evolved ciprofloxacin-resistant Salmonella in the laboratory and identified the mutations that arise during resistance development. We found that resistance does not result from a single change but from multiple adaptations affecting drug efflux, metabolism, and the antibiotic target. Some mutations increased the activity of pumps that remove antibiotics from the cell, while others altered bacterial metabolism and reduced membrane permeability, making it harder for the drug to enter. A duplication in the DNA gyrase subunit GyrB played a particularly important role in maintaining DNA function under antibiotic stress. Together, these results reveal how diverse genetic changes cooperate to generate ciprofloxacin resistance and provide insights that may help guide strategies to combat drug-resistant Salmonella infections.

DNA gyrase↗

PubMed2026

Effect of demographic characteristics on the outcome of prostate cancer salvage radiotherapy: Analysis from a randomized controlled trial.

BACKGROUND: This study investigated the impact of advanced molecular imaging, race, socioeconomic status, and metabolic dysregulation on the outcome of salvage radiotherapy (sRT) for prostate cancer recurrence in a clinical trial setting. METHODS: The authors randomized post-prostatectomy men with detectable prostate-specific antigen to sRT guided by conventional imaging (arm A) or 18F-fluciclovine-positron emission tomography/computed tomography (arm B) and followed them up for up to 48 months to determine failure-free survival (FFS). The authors computed socioeconomic status (SES) and allostatic load (AL) scores to quantify socioeconomic status and level of metabolic dysregulation. They stratified patients by race as African American men (AAM) versus men of other races (MOR) and compared FFS between them using the z-test. RESULTS: Eighty-one (AAM = 29, MOR = 52) and 76 (AAM = 26, MOR = 50) men completed per-protocol sRT in arms A and B, respectively. Across study arms, AAM showed a higher FFS rate than MOR (72.8% [95% CI, 53.8%-85.0%] vs. 58.7% [95% CI, 46.6%-68.9%]; p = .002). In arm A, FFS rate was better for AAM than MOR, (64.0% [95% CI, 34.4%-82.9%] vs. 45.3% [95% CI, 28.8%-60.4%]; p = .008). In arm B, FFS improved for both groups but less so for AAM, (81.5% [95% CI, 57.2%-92.7%] vs. 73.0% [95% CI, 56.3%-84.1%]; p = .131). The authors found lower SES scores and higher AL scores for AAM in both study arms than MOR. CONCLUSION: Despite lower socioeconomic status and higher burden of metabolic dysregulation, in a clinical trial setting that controls for disparities in health care access, AAM have a more favorable sRT outcome than MOR.

Humans↗

PubMed2026

Electrospun Nanofiber Dressings for Diabetic Wounds: From Single-Layer to Intelligent Composite Systems.

Diabetic chronic wounds have become a major challenge for clinical treatment due to their complex pathological microenvironment, including persistent inflammatory response, angiogenesis disorder, excessive oxidative stress, and susceptible infection. Traditional dressings as a passive barrier have difficulty meeting the above multiple treatment needs. Electrospinning technology, with its ability to mimic the fibrous network structure of the natural extracellular matrix (ECM), offers a high specific surface area, controllable porosity, and excellent drug-loading capacity, making it an ideal platform for developing a new generation of multifunctional wound dressings. This article provides a systematic review of the research progress on electrospun nanofiber dressings in the treatment of diabetic wounds, focusing on the design evolution from basic single-layer structures to advanced complex structures and elucidating the mechanisms of action and quantifiable effects of each structural type in addressing specific pathological challenges. We also compared the current status of clinical translation for electrospun dressings with that of other advanced wound care platforms and proposed a standardized preclinical evaluation framework. A large number of research data show that these advanced designs can effectively improve the quality of healing. Finally, this paper points out the challenges faced by this field, such as scalable fabrication, in vivo reliability of smart systems, and long-term biosafety, and provides theoretical basis and technical reference for the design of efficient and intelligent electrostatic spinning diabetic wound dressings.

Nanofibers↗

PubMed2026

Artificial intelligence in treatment prediction for skeletal Class III malocclusion: A systematic review.

In skeletal Class III patients, treatment options range from orthodontics to orthognathic surgery. Choosing the optimal approach requires a comprehensive clinical evaluation, which may be supported by AI tools. The aim of this study was to assess the performance of AI models in predicting the need for orthognathic surgery and in identifying predictors influencing treatment decisions. A PRISMA-guided electronic database search (PubMed, Web of Science; 2009-2024; English/French) was performed to identify studies using machine learning (ML) or deep learning (DL) on cephalometric and clinical data. After screening and assessment for eligibility, 15 studies were critically appraised. Model performance was summarized using accuracy, sensitivity, specificity, and the area under the curve (AUC). ML algorithms (particularly Random Forest and XGBoost) and DL models (ResNet-based convolutional neural networks (CNNs)) achieved high accuracy for predicting surgical need. Frequently selected predictors included Wits appraisal, ANB angle, the maxillomandibular ratio (Mx/Md), overjet, and the divergence of the lower gonial angle. AI methods show promise for assisting treatment decisions in Class III malocclusion, with Random Forest and XGBoost performing well on tabular cephalometric data and CNNs on imaging. Larger, multicentre datasets and external validation are needed to improve reliability, address bias, and support clinical implementation.

Humans↗

PubMed2026

An Update on Inborn Errors of V(D)J Recombination.

V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte-specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical nonhomologous end joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEIs), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase [RAG1, RAG2, and the recently identified RAG cochaperone NudC domain-containing 3 (NUDCD3)], end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development.

Humans↗

PubMed2026

Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article↗

PubMed2026

Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals↗

PubMed2026

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans↗

PubMed2026

Spatially confined electrochemical strategy with DNA-assembled nanogaps for SNP detection.

Accurate detection of low-abundance single nucleotide polymorphisms (SNPs) against a large excess of homologous wild-type sequences requires both selective molecular recognition and effective transduction of small sequence differences into measurable signals. Here, we report a spatially confined electrochemical strategy that couples sequence-selective recognition with size-dependent mass-transport gating. DNA-hybridization-driven self-assembly of gold nanoparticles (AuNPs) forms a three-dimensional self-assembled electrode (3D-SAE) with a DNA-defined interparticle architecture. Competitive probes (SP/WP) convert single-base recognition into distinct molecular-size states: the SNP-associated pathway preferentially triggers a hybridization chain reaction (HCR), generating bulky AuNP-anchored HCR/methylene blue complexes (Au@HCR/MB) with reduced electrochemical accessibility through the porous 3D-SAE, whereas the wild-type pathway does not trigger HCR and maintains a high-current response from more readily accessible MB-containing species. Thus, sequence recognition is translated into a molecular-size difference and subsequently into an electrochemical signal through differential mass transport. Under buffer conditions, the platform achieved a statistically estimated detection limit of ∼0.47 fM and a quantitative range of 1 fM-100 pM. It discriminated a 0.1% mutant abundance in a fragmented genomic-DNA background. The downstream signal-transduction chemistry is enzyme-free and isothermal. This work establishes a mechanistical recognition-size-conversion-mass-transport-gating architecture for electrochemical nucleic acid analysis.

Polymorphism, Single Nucleotide↗

PubMed2026

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged ≥ 65 years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged ≥ 65 years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12 months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p = 0.008), although this finding did not remain statistically significant after Holm correction (adjusted p = 0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p = 0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6 m; 95% CI: 36.8 to 148.3; p = 0.002) and Timed Up and Go performance (-2.27 s; 95% CI: -4.28 to -0.27; p = 0.028), but not for gait speed (0.27 m/s; 95% CI: -0.05 to 0.59; p = 0.099). At 12 months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12 months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans↗

PubMed2026

Mitochondrial translocation of DNMT3L suppresses oxidative phosphorylation and restrains megakaryopoiesis.

DNMT3L, a catalytically inactive member of the DNA methyltransferase family, is identified here as a negative regulator of megakaryopoiesis. In K562 cells undergoing PMA-induced megakaryocytic differentiation, DNMT3L protein levels declined progressively, and shRNA-mediated depletion enhanced differentiation, whereas overexpression attenuated it. Consistent with these findings, Dnmt3l-knockout mice exhibited elevated peripheral blood platelet counts and expanded bone marrow megakaryocytes. Mechanistically, megakaryocytic differentiation triggered rapid mitochondrial translocation of DNMT3L within 6 h; mitochondrial DNMT3L suppressed oxidative phosphorylation (OXPHOS) capacity and ATP production and downregulated mitochondrial-encoded genes spanning Complex I, III, IV, and ATP synthase, without altering mitochondrial DNA copy number. This metabolic suppression was mediated through compartment-specific remodeling of DNMT3L-containing protein complexes: upon differentiation, DNMT3L selectively dissociated from DNMT1 and DNMT3B in mitochondria, relieving the repressive constraint on OXPHOS, whereas in the nucleus DNMT3L remained associated with DNMT3A, which concomitantly accumulated during differentiation. These findings reveal a previously unrecognized mechanism by which a catalytically inactive epigenetic co-regulator spatially redistributes to coordinate mitochondrial metabolic output with nuclear epigenetic control, thereby facilitating terminal megakaryocytic maturation.

Animals↗

PubMed2026

Optimizing eco-engineering pedogenesis of bauxite residues: Synergistic effects of humus and FeSO4/sulfur on microbial community and function.

Eco-engineered pedogenesis represents a promising approach for soil amelioration of bauxite residues (BRs) through exogenous organic matter. However, the role of humus in mediating this process remains poorly understood, significantly impeding the eco-engineering rehabilitation of BRs. In this study, we conducted pot experiments and subsequent microbial analysis to evaluate the individual improvement of humic acid (HA), fulvic acid (FA), and corn straw (SWZ) on the BRs' pedogenesis. High-throughput sequencing analysis revealed that both FA and SWZ were more effective than HA in steering microbial community assembly, as community diversity, dominant taxa enrichment, and species' interaction were all significantly higher (p < 0.05) in the FA/SWZ treatments than in HA treatments. Notably, the combination of FA with FeSO4 specifically enriched halophilic taxa, while FA coupled with sulfur (S) significantly improved the connectivity and complexity of the microbial network, as the average connection degree increasing from 1.008 to 1.113. Hydrolytic enzyme activity assays further indicated that FA, especially when combined with S, was the most effective treatment in restoring microbial function during BR pedogenesis. These findings highlight FA as a critical driver of microbial restructuring and functional recovery in BRs. Moreover, its efficacy can be enhanced by co-amendment with FeSO4 or S. This study provides important theoretical and practical insights for optimizing organic-inorganic amendment strategies to accelerate the eco-engineering pedogenesis of bauxite residues.

Humic Substances↗

PubMed2026

What Constitutes Effective Support and Provision Within Day Service Centres for People With Intellectual Disabilities? A Systematic Review of Qualitative Research.

BACKGROUND: This review aimed to investigate the effectiveness and quality of support and provision within day service centres for people with intellectual disabilities. METHOD: The International Bibliography of the Social Sciences, Scopus and PsycInfo databases were searched in August 2024, and the results were reported according to the PRISMA guidelines. Peer-reviewed, English-language, qualitative studies that investigated the effectiveness of day service provision for people with intellectual disabilities in non-residential settings were considered for review. Methodological quality of the included studies was assessed using the JBI Critical Appraisal Tool for qualitative research. Qualitative themes were identified through thematic analysis and synthesised using the ConQual approach. RESULTS: Fourteen studies were included and four key themes emerged: 'perceptions of service quality'; 'community-orientation, integration, and empowerment'; 'challenging behaviours and safety'; and 'staff-centred factors and job satisfaction'. Confidence in the evidence was 'very low' for 3/4 themes, while there was 'moderate' confidence in the evidence related to the theme 'perceptions of service quality'. CONCLUSIONS: Day service centres for people with intellectual disabilities may enhance their effectiveness and quality of provision by concentrating on promoting communication, engagement, relationships, social networks and community integration. Addressing the methodological shortcomings and incomplete reporting of related research in future would contribute to improvements in overall confidence in the evidence base. This can then be better used to inform and further enhance day service provision for people with intellectual disabilities.

Humans↗

PubMed2026

Integrating genomic distance analyses in the description of a new family, genus, and species of sponge-associated antipatharians (black corals).

Antipatharians (black corals) are among the least studied coral groups, with much of their diversity still undescribed. Here, we present an integrative morphological, phylogenomic and genomic distance study of deep-sea antipatharians sampled in high seas areas of the North Pacific Ocean and from New Zealand's Exclusive Economic Zone. These corals grow on hexactinellid sponges - a unique characteristic in the order Antipatharia. Using a dataset of ultra-conserved elements and exons, combined with morphological analyses, we reconstruct phylogenomic relationships and formally describe a new family (Eidikopathidae fam. nov.), a new genus (Eidikopathesgen. nov.), and two new species (E. korallispongiasp. nov., E. zealandkoralliasp. nov.). Morphologically, the new family is distinguished by a corallum consisting of a network of loose branches that fuse with the sponge skeletal framework. Phylogenomic analyses recovered consistent topologies with strong nodal support, corroborating the distinct evolutionary placement of this sponge-associated lineage. Pairwise genomic distances estimated using the Tamura-Nei model were concordant with patristic genomic distances, identifying Pteridopathidae as the genetically closest family to Eidikopathidae fam. nov., followed by Myriopathidae and Stylopathidae, which were recovered as sister families in the phylogeny. This pattern shows that genomic distance complements, rather than simply mirrors, tree topology by quantifying accumulated sequence divergence among lineages. Together, these results provide the first genomic distance framework for Antipatharia, offering a baseline for future systematic, evolutionary, and biodiversity studies on this fundamental shallow, mesophotic and deep-sea coral group.

Animals↗