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PubMed2026

Genome-Wide Impact of Human DBR1 Depletion on RNA Processing Networks Reveal a Connection Between Pre-mRNA Splicing, mRNA Surveillance and Stress Granule Dynamics.

The RNA lariat debranching enzyme DBR1 is essential for intron turnover and RNA metabolism, yet its broader impact on transcriptome regulation remains incompletely defined. To elucidate the consequences of DBR1 depletion, we performed transcriptome-wide RNA sequencing of DBR1-knockdown and wild-type HEK293 cells. Differential expression analysis revealed widespread perturbations in pathways linked to RNA splicing, mRNA surveillance, translational control, and stress-granule biology. Many of the most significantly altered transcripts encode splicing factors and RNA quality-control components, underscoring DBR1's influence on post-transcriptional regulation. Alternative splicing analysis showed changes across multiple event types, with exon skipping accounting for >50% of events, followed by mutually exclusive exons, alternative 5' and 3' splice sites, and retained introns, indicating that DBR1 depletion induces pervasive splicing defects. Direct spliceosome inhibition using isoginkgetin (blocks tri-snRNP recruitment) and pladienolide B (targets SF3B1) reproduced the DBR1-KD mis-splicing patterns of cell signaling genes and factors involved in RNA metabolism, supporting a functional link between DBR1 activity and alternative splicing. Notably, DBR1 knockdown revealed a subset of transcripts that are both NMD-sensitive and enriched within stress granules. Consistent with this observation, G3BP1 immunopurification and confocal microscopy further support a role for DBR1 and UPF1 in stress-granule dynamics, suggesting that these factors may participate at distinct stages to influence mRNA fate under stress conditions. Together, these findings indicate that DBR1 functions beyond lariat RNA turnover as a common regulator of RNA processing, transcriptome stability, and stress granule homeostasis, revealing intricate crosstalk between RNA splicing and RNA quality control pathways in human cells.

Humans↗

PubMed2026

TNF-NF-κB signaling mediates immune-biomineralization crosstalk during shell repair under ocean acidification in Mytilus edulis.

Ocean acidification (OA) impairs biomineralization in bivalves, but its effects on immune-biomineralization crosstalk during shell repair remain unknown. Here, we exposed adult Mytilus edulis bearing standardized shell perforations to three pH levels (8.1, 7.9, and 7.7) for up to 40 days. OA slowed early repair and caused microstructural disorganization and an approximately 87% reduction of compressive strength at pH 7.7, yet the damaged area appeared largely closed by day 15, suggesting a decoupling between morphological closure and functional recovery. In addition, transcriptomic profiling of hemocytes and mantle tissue, based on an average of 6.5 Gb of clean reads per sample mapped to the M. edulis reference genome (NCBI Assembly GCF_000511035.1), revealed that these shell-level defects were accompanied by coordinated immune and metabolic reprogramming. Hemocytes, the primary immune effector cells of bivalves, exhibited pH- and time-dependent shifts with moderate acidification (pH 7.9) promoting inflammatory transcripts, whereas severe acidification (pH 7.7) suppressed these signals while upregulating stress-associated pathways; both treatments consistently downregulated lysosomal proteases and NF-κB negative regulators. The mantle, a primarily mineralizing organ, paradoxically upregulated immune-related genes while suppressing oxidative phosphorylation and extracellular matrix pathways. This tissue-level imbalance, with hemocytes recruited but functionally constrained and mantle metabolically suppressed yet immunologically activated, points to TNF-NF-κB pathway modulation as a key mediator of shell repair under acidification. Our findings demonstrate that visible shell closure masks underlying structural and mechanical failure, and that immune regulation, rather than simple suppression or activation, critically shapes the repair outcome. These results advocate for multifunctional indicators beyond closure area to assess shell integrity in acidified marine environments.

Animals↗

PubMed2026

Uce-based phylogeny and classification of Megachilini.

The generic-level classification of the bee tribe Megachilini (Megachilidae) has remained controversial due to poor phylogenetic resolution at the base of the group, particularly among the brood parasitic genera and the numerous dauber ("Chalicodoma s. l.") lineages. We present a phylogenomic analysis of Megachilini based on ultraconserved elements (UCEs), sampling 52 ingroup taxa with emphasis on the dauber lineages. We also present a combined UCE + six-gene analysis to improve taxon coverage, resulting in a dataset with 127 ingroup taxa. Maximum likelihood, coalescent, and Bayesian analyses of multiple UCE matrices recover largely congruent topologies with substantially improved support relative to previous studies. Our results strongly support the monophyly of Megachilini, the early divergence of Noteriades and Gronoceras, and a single origin of brood parasitism. All remaining non-parasitic Megachilini form a moderately supported clade sister to the brood parasitic lineage. The leafcutter bees are monophyletic and nested within dauber lineages. Several major dauber clades are consistently recovered, including an exclusively Australian clade corresponding to the Hackeriapis group of subgenera, while several recognized subgenera are paraphyletic. The lineage known as Morphella, previously placed in synonymy with the subgenus Callomegachile, was not closely related to that subgenus and is here treated as a valid subgenus. Divergence-time analyses place the crown age of Megachilini in the late Eocene to early Oligocene, with major extant lineages diversifying during the Miocene. Limited morphological diagnosability of several clades indicates that splitting non-parasitic lineages into numerous genera would result in an impractical classification that would widen the gap between taxonomists and non-specialists and exacerbate the taxonomic impediment in bees. We therefore advocate retaining a single genus Megachile for non-parasitic Megachilini (excluding Noteriades and Gronoceras), as the classification best supported by phylogenomic evidence and most robust to future taxon sampling.

Animals↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2026

Fasting-refeeding regimes induce compensatory growth and muscle transcriptomic remodeling in juvenile Qihe gibel carp (Carassius gibelio var. Qihe).

Compensatory growth, an important adaptive response in fish, holds considerable potential for improving feeding efficiency in aquaculture. To identify an optimal fasting-refeeding strategy for juvenile Qihe gibel carp (Carassius gibelio var. Qihe) and to clarify the mechanisms underlying the compensatory growth, we divided two-month-old fish into four groups, namely S0 group (continuous feeding for 28 days), S2 group (4 cycles of 2-day fasting followed by 5-day refeeding), S4 group (fasting for 4 days followed by refeeding for 24 days), and S8 group (fasting for 8 days followed by refeeding for 20 days), then growth performance, muscle tissue morphology, biochemical responses, and muscle transcriptomic profiles under different feeding regimes were investigated. After a 28-day aquaculture experiment, fish in the S4 group exhibited significantly greater body length and weight than those in the S0, S2, and S8 groups, indicating over-compensatory growth. Histological analysis further showed that muscle growth in the S4 group was mainly associated with myofiber hyperplasia. Different feeding regimes also induced distinct changes in hepatic antioxidant and metabolic enzyme activities, as well as intestinal digestive enzyme activities. Transcriptome analysis revealed that the forkhead box O (FoxO) signaling pathway was significantly enriched during compensatory growth. Key genes, including serum/glucocorticoid regulated kinase 1 (sgk1) and insulin receptor substrate 1 (irs1), were predicted to play important roles in this process. Overall, these results indicate that fasting for 4 days followed by refeeding for 24 days (the S4 regime) is the optimal strategy for inducing compensatory growth in juvenile Qihe gibel carp. This study provides new insights into the morphological, physiological, and molecular basis of compensatory growth and offers a scientific foundation for developing efficient and sustainable feeding strategies for this species.

Animals↗

PubMed2026

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals↗

PubMed2026

METTL14-mediated m6A modification of CCNE1 accelerates progression of myelodysplastic syndromes via MAPK-ERK and PI3K-AKT signaling pathways.

BACKGROUND: N6-methyladenosine (m6A) is the most common RNA modification and plays a key role in the initiation, progression, and relapse of multiple cancers, including hematologic malignancies. However, the role of m6A and m6A regulatory genes in myelodysplastic syndromes (MDS) remains unclear. This study aims to elucidate the function and molecular mechanism of methyltransferase METTL14 in MDS. METHODS: RT-qPCR was used to assess the expression of multiple m6A regulators, focusing on METTL14 in MDS patients and cell lines. METTL14 overexpressing and knockdown cell lines were established, and CCK-8, EdU, and flow cytometry assays were performed to explore the biological functions of METTL14.Dot blot, MeRIP-Seq, MeRIP-qPCR, RT-qPCR, and Western blot were employed to investigate the underlying molecular mechanism. RESULTS: Dysregulation of multiple m6A regulators was observed in MDS, among which METTL14 was upregulated. Elevated METTL14 expression increases MDS risk and adverse prognosis, emerging as a biomarker for poor prognosis. METTL14 promoted proliferation and cell-cycle progression of MDS cells while inhibiting apoptosis; corresponding changes were observed in cell cycle and apoptosis markers. METTL14 regulated cellular m6A levels. Downstream targets of METTL14 were enriched in cell cycle-related pathways, with CCNE1 identified as a critical target. Knockdown of METTL14, actinomycin D, or S-adenosylhomocysteine treatment reduced CCNE1 mRNA and protein levels. Furthermore, METTL14 activated MAPK-ERK and PI3K-AKT signaling via CCNE1 in an m6A-dependent manner, thereby promoting proliferative MDS cells' capacity. CONCLUSIONS: This study delineates a METTL14/m6A/CCNE1 signaling axis in MDS progression and suggests that METTL14-mediated m6A modification may be a potential therapeutic target for MDS.

Humans↗

PubMed2026

Enhanced risk stratification in hypertrophic cardiomyopathy through the integration of extracellular volume fraction on cardiovascular magnetic resonance.

AIMS: This study investigated the incremental prognostic value of cardiovascular magnetic resonance (CMR)-derived extracellular volume fraction (ECV), a marker of diffuse interstitial fibrosis, beyond late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analysed 990 consecutive HCM patients (median age 58 years, male 68.3%) who underwent CMR between 2012 and 2024. LGE and global ECV were quantified, and their associations with the primary endpoint of HCM-related events-a composite of sudden cardiac death (SCD) events, heart failure (HF) events, and HCM-related death-were assessed. During a median follow-up of 3.2 years, 64 (6.5%) patients experienced the primary endpoint. While LGE (median 7.1%, IQR 2.3-16.9%) and ECV (median 29.0%, IQR 26.6-32.0%) were moderately correlated (R = 0.604, P < 0.001), both were significantly associated with increased risk of the primary endpoint and individual outcomes of SCD and HF events, and optimal cutoffs were determined as LGE ≥ 27% and ECV ≥ 35%. Patients with ECV ≥ 35% had more symptoms, a more severe phenotype with greater systolic and diastolic dysfunction, and more pathogenic gene variants. Notably, ECV remained a significant predictor of the primary endpoint (adjusted HR 1.08, 95% CI 1.02-1.15, per 1%) after adjustment for key disease variables, including left ventricular ejection fraction and LGE. Elevated ECV effectively identified high-risk individuals even among lower-risk subgroups, including those with low LGE burden. CONCLUSION: Increased ECV is an independent predictor of HCM-related outcomes. ECV may serve as a novel imaging biomarker to refine risk stratification in HCM patients who do not meet traditional LGE-based high-risk criteria.

Humans↗

PubMed2026

In silico identification of DNMT1 inhibitors from the PlantCyc database through computational approach to assess the anti-cancer potential of nutraceutical compounds in breast cancer.

Breast cancer accounts for a disproportionate share of global cancer-related deaths, with 670,000 fatalities and 2.3 million new diagnoses recorded in women during 2022 alone. Existing treatment modalities carry considerable toxicity burdens, and resistance to available agents remains an unresolved clinical problem. DNA methyltransferase 1 (DNMT1), the enzyme chiefly responsible for maintaining genome-wide methylation patterns during DNA replication, has been mapped out as a high-value target in breast cancer because its dysregulation silences tumour suppressor genes through promoter hypermethylation. The present work involves hierarchical in silico workflow to screen 4549 plant-derived compounds from the PlantCyc database (v16.0.3) against the human DNMT1 catalytic domain (PDB ID: 4WXX). Ten top-scoring compounds were taken forward for molecular docking via AutoDock Vina; Quercetin and Kaempferol both recorded the highest binding affinities at -9.5 kcal/mol, Wogonin (-9.3 kcal/mol) and Xanthohumol (-8.1 kcal/mol) also emerged as strong binders. Pharmacokinetic evaluation using ADMET-AI confirmed that all 10 compounds met Lipinski's rule of five, with human intestinal absorption values at or above 0.98. Wogonin and Xanthohumol were selected for a 100 ns all-atom molecular dynamics (MD) simulation in GROMACS due to their well-rounded ADMET profiles and limited existing data on their specific interactions with DNMT1 in breast cancer. Across all measured trajectory metrics, backbone RMSD, residue fluctuation, radius of gyration, solvent-accessible surface area, and intermolecular hydrogen bond count, Wogonin formed a more stable, compact complex. These findings suggest that Wogonin and Xanthohumol are non-toxic nutraceutical candidates suitable for DNMT1 targeted epigenetic therapy, with computational foundation strong enough to facilitate future in vitro and in vivo validation work.

Humans↗

PubMed2026

Feasibility of routine clinical liquid-based cytology for lung cancer compact panel testing.

BACKGROUND: The Lung Cancer Compact Panel (cPANEL) is a recently approved highly sensitive multiplex gene panel in Japan that supports both DNA- and RNA-based next-generation sequencing. Although cytological specimens are acceptable for cPANEL, unfixed cell pellets or dedicated preservation tubes are typically recommended. However, evidence remains limited regarding whether residual liquid-based cytology (LBC) cell suspensions prepared for routine cytological diagnosis can be used directly for cPANEL testing without dedicated molecular preservation or additional preanalytical processing. In this study, we evaluated the feasibility of applying LBC specimens that are widely used in contemporary clinical practice to cPANEL. METHODS: We analyzed DNA and RNA quality in 69 clinical LBC specimens. Among these, 51 specimens containing non-small cell lung cancer cells with previously determined driver alteration status were subjected to cPANEL testing to evaluate assay concordance with clinical companion diagnostic results. RESULTS: DNA integrity was generally well preserved (DNA Integrity Number [DIN]: 6.2 ± 1.5). In contrast, RNA integrity showed greater variability (DV200: 16.4 ± 12.1%). ThinPrep-fixed specimens demonstrated lower DIN and DV200 values compared with CytoRich Red-fixed specimens. Although all samples successfully passed the DNA-based cPANEL assay, six cases (11.8%) failed the RNA-based assay, with RNA yield being a major contributing factor. Among the 46 evaluable specimens, concordance was 95.7% and sensitivity was 92.3%, or 88.9% including RNA module failures as cPANEL-negative. CONCLUSIONS: With appropriate fixative selection and adequate cellularity, cPANEL using clinical LBC specimens may serve as a practical diagnostic platform. We demonstrated that routine LBC specimens can be directly applied to cPANEL without special preanalytical processing.

Humans↗

PubMed2026

Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.

BACKGROUND: Meier-Gorlin-syndrome (MGORS) is a rare cause of primordial dwarfism stemming from pathogenic variants in genes involved in DNA replication. The classic clinical triad is microtia, absent patella and short stature. MGORS can mimic endocrine causes of short stature or delayed/atypical pubertal development. METHODS: We report two new cases of MGORS. A systematic literature search of all cases published up to 31 March 2026 was done to identify the cases reporting any endocrinopathy or hormonal therapy, focussing on growth-hormone-deficiency (GHD) and response to growth hormone (GH). RESULTS: We describe a 14 year-old girl, the first MGORS case with CDC6 variant and mammary hypoplasia. Another 11-year old boy with GMNN variant had severe short-stature with GHD and had significant height improvement with GH. Among 29 cases (out of ~150 published), the classic triad was absent in 18.5%. Short stature was almost universal (median height-Z-score -4.4), with 70% exhibiting delayed bone age, 42.9% low IGF-1 and 35.3% GHD. Among 10 GH-treated cases with response data, 6 had reported improvement in height-SDS/growth-velocity. Those with GHD and delayed bone age were more likely to benefit from GH. Among females, all post-pubertal cases had mammary hypoplasia, while 23.5% had clitoromegaly with hypoplastic labia. Among males, cryptorchidism, hypoplastic scrotum and micropenis were common. However, gonadal hormones and gonadotrophins were normal. Data on the effect of estrogen on hypoplastic mammary glands or labia was variable. CONCLUSION: MGORS should be kept in mind as a differential of multiple endocrinopathies. Cases of MGORS should undergo screening for GHD. Available data, mostly from case-reports or small series, suggest that response to GH has been reported in some individuals, particularly where GHD or delayed bone age was present, but evidence remains very limited.

Humans↗

PubMed2026

Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.

PURPOSE/BACKGROUND: Pharmacogenomics (PGx), or the use of genetic information to assess drug-gene interactions, is an important step toward precision medicine. It is unclear if clinician use of PGx yields better outcomes for their patients. This study compared the effectiveness of combinatorial PGx-guided plus guideline-informed treatment (PGx+GIT) with guideline-informed treatment (GIT) alone to improve well-being in individuals with major depressive disorder. METHODS/PROCEDURES: Eligible participants (N=201) were randomized to PGx+GIT or GIT alone. PGx was measured with the proprietary GeneSight combinatorial test. PGx+GIT participant clinicians received test results within 2 business days to inform decisions about medication changes. Participants completed the World Health Organization Well-Being Index (WHO-5), Patient Health Questionnaire (PHQ-9), and PROMIS Profile physical functioning and social roles and activity domains every 2 weeks for 2 months and then every 2 months for the remaining 10 months. Monthly medication changes operationalized as necessary clinical adjustments were tracked with the medication recommendation tracking form. FINDINGS/RESULTS: Both groups improved average well-being over the 12-month study period (model-based change in WHO-5 per log (week) [95% CI]: 4.1 [3.3, 5.0] PGx+GIT and 4.8 [4.0, 5.5] GIT). PGx+GIT did not result in superior improvement in well-being (model-based difference [95% CI]: -0.6 [-1.8, 0.5], P =0.270), or any secondary outcomes. The effect of randomized treatment on well-being was not moderated by depression severity, number of previous failed medications for major depressive disorder, or presence of a comorbid condition. IMPLICATIONS/CONCLUSIONS: These data suggest PGx+GIT was not superior to GIT alone, possibly due to a ceiling effect of GIT, or PGx did not yield better results.

Humans↗

PubMed2026

Microbial allies in a cotton pest: A descriptive account of associated microbiota dynamics in Dysdercus cingulatus across development.

BACKGROUND: Hemipteran insects harbour several symbiotic partners, mainly bacteria, which play pivotal roles for hosts like dietary provision, support overall physiology, xenobiotic degradation and manipulate/regulate behaviour. Most of these symbionts usually reside and operate from the digestive tracts of the animals. Cotton is one of the major cash crops in India and Dysdercus cingulatus (D. cingulatus) though a secondary pest, is causing significant destruction of cotton bolls, poor lint quality and reduce oil content of seeds. Premature opening of cotton bolls often leads to bacterial and fungal infections, thus resulting in extensive economic loss worldwide. D. cingulatus is a hemimetabolous insect that comprises of developmental stages like egg, nymph (5 instar stages), and adult. The present work explored the ontogeny specific diversity in the associated microbiota and predicted their probable functional inputs in D. cingulatus. RESULTS: The data obtained using 16S rRNA gene sequencing (NovaSeq 6000) revealed presence of members of Proteobacteria (65.83%), Firmicutes (24%), Actinobacteria (10%) phyla throughout the ontogeny of D. cingulatus. Highest alpha diversity of these symbiotic bacteria was recorded in the third instar nymphs in contrast to rest of the developmental stages. Among all the observed genera, Stenotrophomonas, Hungatella and Glutamicibacter were predominant from egg to adult stages. MicFunPred, a tool used for predicting the probable functional inputs of these symbionts, hinted at their probable stage specific contribution in crucial biochemical pathways such as polyketide biosynthesis, ascorbate/aldarate metabolism, pentose phosphate and glyoxylate cycles, steroid hormone and peptidoglycan biosynthesis, and glycolysis/pyruvate metabolism. CONCLUSIONS: The primary investigations on the ontogenetic composition and diversity of associated microbiota, suggest dynamic shifts in D. cingulatus, concurrent with their probable functions/roles in the host development and metabolism. To the best of our knowledge, this is the first report on symbiotic microbiota variation across the developmental stages of D. cingulatus that provides preliminary descriptive observations that may guide future functional and experimental investigations into microbiota-based pest management.

Animals↗

PubMed2026

Genomic and food-safety evaluation of Staphylococcus chromogenes in Chinese dairy milk.

Non-aureus staphylococci and mammaliicocci (NASM) cause mastitis and may contaminate milk and dairy products. Milk samples (n = 1916) from cows with subclinical or clinical mastitis (SCM and CM, respectively) were collected from 28 large-scale (> 500 lactating cows) Chinese dairy farms. Overall, 999 NASM isolates representing 19 species were identified by MALDI-TOF MS and cpn60 sequencing, with Staphylococcuschromogenes, Mammaliicoccus sciuri and Staphylococcus haemolyticus being most prevalent. Antimicrobial resistance (AMR) was determined with disc diffusion; non-susceptible to penicillin was most common (SCM, 30% and CM, 29%) whereas cefoxitin non-susceptible NASM accounted for 8-10% of isolates; among these, 12.5% carried mecA but none carried mecC. Galleria mellonella was used to assess virulence of 78 strains of S. chromogenes, a dominant species; subsequently, 32 strains, representing higher- and lower-virulence in the Galleria model, were selected for whole-genome sequencing and comparative genomics. S. chromogenes isolates from CM had higher virulence (p < 0.05) than those from SCM. The 32 genomes comprised 20 sequence types, indicating high genetic diversity. No robust genomic marker of Galleria virulence phenotype was identified in this selected WGS subset. Acquired resistance genes (n = 5) were detected, including a first report of fusC in S. chromogenes; the fusC-positive isolate had an elevated fusidic acid MIC (8 mg/L). Although S. chromogenes persisted in milk at 4 °C, pasteurization (64 °C for 30 min) reduced viable counts to below detection. This study provided new insights into the prevalence, AMR, genomic diversity, and dairy-chain relevance of milk-derived NASM, particularly S. chromogenes. However, the genomic findings were based on an intentionally selected WGS subset and should be interpreted as hypothesis-generating rather than population-representative.

Animals↗

PubMed2026

Real-world clinical utility of exome sequencing in pediatric drug-resistant epilepsy: Experience from a tertiary center in Thailand.

BACKGROUND: Genomic testing has increasingly contributed to the diagnosis and management of pediatric drug-resistant epilepsy (DRE), particularly in patients with suspected genetic etiologies. This study evaluated the diagnostic yield and real- world clinical utility of whole-exome sequencing (WES) in children with DRE. METHODS: Children with DRE and seizure onset before 15 years of age were enrolled between January 2020 and December 2023. Clinical data, including demographics, seizure characteristics, developmental history, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and prior investigations, were reviewed. WES was performed in all probands and, when available, their parents. Variants were interpreted according to standard guidelines. Clinical utility and 1-year seizure and developmental outcomes were assessed from follow-up records. RESULTS: Fifty-six patients (23 males, 33 females) were included. The median age at seizure onset was 1 year (interquartile range [IQR] 0.3-4 years), and 96.4% had developmental comorbidities. Pathogenic or likely pathogenic variants were identified in 39% (22/56), with the highest diagnostic yield in children with seizure onset before 3 years of age. Channelopathies accounted for most genetically solved cases (68%), predominantly involving sodium channel genes. Genetic diagnoses provided clinical utility in 73% (16/22) of solved cases by guiding treatment and precision management. At 1-year follow-up, genetically solved patients showed more favorable seizure and developmental outcomes than those with genetically unsolved patients. CONCLUSION: WES achieved a 39% diagnostic yield and substantial clinical utility in pediatric DRE, particularly in early-onset and channelopathy-related disorders. These findings support early molecular diagnosis to facilitate genotype-informed management in appropriately selected children. However, the more favorable developmental and seizure outcomes observed in genetically solved patients should be interpreted with caution, as they may have been influenced by multiple factors beyond genetic diagnosis. In resource-limited settings, careful clinical phenotyping remains essential for treatment decisions and for prioritizing children for genomic testing.

Clinical utility↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗

PubMed2026

Comparative assessment of post-transport disease susceptibility in Asian seabass (Lates calcarifer): Associations with oxidative stress, immune responses, gut microbiota, and tissue pathology.

Stress is a crucial factor that affects aquaculture systems, particularly during transportation, which often leads to deteriorated fish health and reduced survival rates. This study aimed to investigate the comparative differences in physiological changes, oxidative stress parameters, and immune responses between clinically healthy and diseased Asian seabass (Lates calcarifer) following commercial transportation. The study compared the health status of fish after transportation, categorized into healthy (Healthy) and diseased (Disease) groups. Assessments were conducted on oxidative stress parameters, immune responses, gut microbiota composition, and tissue pathology. The results showed that diseased fish exhibited significantly higher oxidative stress levels (P < 0.05), as indicated by an increase in malondialdehyde (MDA) levels and altered antioxidant and redox-related markers, including superoxide dismutase (SOD), nitric oxide (NO), catalase (CAT), glutathione (GSH), glutathione reductase (GR), and glutathione peroxidase (GPx), measured across multiple target tissues (head kidney, gills, liver, intestine, and brain), compared with healthy fish. Furthermore, the expression of immune-related genes was significantly downregulated in diseased fish after transportation, indicating immune suppression. In contrast, healthy fish maintained a more balanced immune response, which may partially mitigate the adverse effects of transport-induced stress. Gut microbiota analysis revealed that diseased fish had a significant reduction in beneficial bacteria such as Cetobacterium somerae and Bacillus spp., accompanied by a significant (P < 0.05) increase in opportunistic pathogens including Aeromonas spp., Photobacterium spp., and Vibrio spp. Histopathological examination showed severe damage in the gills, liver, and intestines of diseased fish (P < 0.05), while only minor tissue alterations were observed in healthy fish. Overall, the findings indicate that post-transport diseased Asian seabass exhibit marked oxidative stress, impaired antioxidant defense, altered immune responses, gut microbial dysbiosis, and multi-organ tissue damage compared with clinically healthy post-transport fish. These results suggest that deterioration of transport conditions may contribute to post-transport morbidity and disease susceptibility.

Animals↗

PubMed2026

A systematic review and network meta-analysis of single nucleotide polymorphisms associated with oral submucous fibrosis risk.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic and insidious oral disease characterized by hyalinization of the subepithelial connective tissue and progressive fibrosis of the oral submucosa. It is a precancerous condition of oral squamous cell carcinoma. Studies have demonstrated that single nucleotide polymorphisms (SNPs) are closely associated with susceptibility to OSF. This study aims to comprehensively evaluate the association between SNPs and OSF risk and to rank the strength of the association between different genetic models and OSF susceptibility. METHODS: Literature related to OSF was comprehensively searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wangfang databases up to July 2025. Full-text case-control studies with patients diagnosed with OSF were included. Quality assessment was performed to evaluate the risk of bias. RevMan 5.4, GeMTC 0.14.3, and STATA 17.0 were used for the pairwise and Bayesian network meta-analysis. RESULTS: A total of 24 studies with 2545 cases and 3772 controls, covering 13 SNPs in 11 genes, were included in our meta-analysis. We found that CYP1A1 rs4646903:T>C, CYP1A1 rs1048943:A>G, GSTT1 null genotype, GSTM1 null genotype, and XRCC3 rs861539:C>T were associated with an increased risk of OSF, while MMP2 rs243865:C>T and MMP3 rs3025058: 5A>6A were associated with a decreased risk of OSF. Further Bayesian network meta-analysis indicated the top 5 genetic models with the highest association with OSF risk in network group 1 were the dominant model, homozygous model, allelic model, and recessive model of CYP1A1 rs1048943:A>G (ranked 1-4), and the heterozygous/dominant model of CYP1A1 rs4646903:T>C (both ranked 5). While the allelic models of XRCC3 rs861539:C>T and MMP3 rs3025058: 5A>6A ranked first for predicting OSF in group 2 and group 3, respectively. CONCLUSION: Some specific SNPs are significantly related to the risk of OSF. Among them, the dominant model of CYP1A1 rs1048943:A>G may be the most strongly associated genetic model with OSF risk. Future large-sample, well-designed studies with detailed genotype data are needed to validate the roles of these SNPs in OSF risk.

Humans↗