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PubMed2026

Novel association of NAV3 with dilated cardiomyopathy and its role in cardiac fibrosis.

A genome-wide association study (GWAS) identified neuron navigator 3 (NAV3) as a potential genetic determinant of myocardial recovery in dilated cardiomyopathy (DCM). This study aimed to understand its functional role in cardiac pathophysiology by leveraging omics approaches. Single-cell RNA-seq transcriptomic data from previously published adult human hearts indicate that NAV3 expression is highest in cardiac fibroblasts, suggesting its functional role in these cells. In vitro, stimulation of primary human ventricular cardiac fibroblasts with transforming growth factor β1 (TGF-β1) induced NAV3 expression in a dose and time-dependent manner. Small-interfering-RNA-mediated knockdown of NAV3 significantly attenuated TGF-β1-induced fibroblast activation, reducing the expression of α-smooth muscle actin (α-SMA), collagens, and fibronectin. RNA sequencing of NAV3-silenced fibroblasts, confirmed by Western blot, revealed upregulation of cell cycle regulators and downregulation of profibrotic markers, suggesting that NAV3 facilitates TGF-β1-induced cell cycle arrest and fibroblast-to-myofibroblast transition. Notably, NAV3 silencing did not alter canonical SMAD2/3 phosphorylation, implying a role for NAV3 in modulating fibrotic signaling through other pathways. Our findings provide functional and mechanistic insights into NAV3's novel role in cardiac fibrosis, showing that reduced NAV3 expression attenuates TGF-β1-mediated fibroblast activation by regulating cell cycle signaling. These results support further investigation of NAV3 as a potential modulator of cardiac fibrosis and myocardial recovery in DCM.NEW & NOTEWORTHY This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.

Humans↗

PubMed2025

Escape from TGF-β-induced senescence promotes aggressive hallmarks in epithelial hepatocellular carcinoma cells.

Transforming growth factor-β (TGF-β) signaling and cellular senescence are key hallmarks of hepatocellular carcinoma (HCC) pathogenesis. Despite provoking senescence-associated growth arrest in epithelial HCC cells, elevated TGF-β activity paradoxically correlates with increased aggressiveness and poor prognosis in advanced tumors. Whether the transition between these dichotomous functions involves modulation of the senescence phenotype during disease progression remains elusive. Exploiting the epithelial HCC cell line Huh7 as a robust model, we demonstrate that chronic exposure to TGF-β prompts escape from Smad3-mediated senescence, leading to the development of TGF-β resistance. This altered state is characterized by an optimal proliferation rate and the acquisition of molecular and functional traits of less-differentiated mesenchymal cells, coinciding with differential growth capacity in 2D and 3D culture conditions, epithelial-to-mesenchymal transition (EMT), and increased invasiveness in vitro, and metastasis in vivo. Mechanistically, resistant cells exhibit defective activation and nuclear trafficking of Smad molecules, particularly Smad3, as ectopic activation of the TGF-β/Smad3 axis is able to reinstate TGF-β sensitivity. An integrated transcriptomic landscape reveals both shared and distinct gene signatures associated with senescent and TGF-β resistant states. Importantly, genetic ablation and molecular studies identify microtubule affinity regulating kinase 1 (MARK1) and glutamate metabotropic receptor 8 (GRM8) as critical modulators of the resistance phenomenon, potentially by impairing spatiotemporal signaling dynamics of Smad activity. Our findings unveil a novel phenomenon wherein epithelial HCC cells may exploit senescence plasticity as a mechanism to oppose TGF-β anti-tumor responses and progress towards more aggressive HCC phenotypes.

Humans↗

PubMed2026

Bacterial polar metabolites modulate β-amyloid toxicity and cholinergic dysfunction in models of Alzheimer's disease.

Alzheimer's disease is characterized by progressive neurodegeneration driven by β-amyloid (Aβ) toxicity, oxidative stress, and cholinergic dysfunction. In this study, we investigated whether polar metabolites derived from a cultivable bacterial isolate could modulate Aβ-associated neurodegenerative phenotypes in complementary experimental models. A bioactivity-guided approach identified an aqueous fraction with high antioxidant capacity in DPPH, FRAP, and ORAC assays. In a transgenic Drosophila melanogaster model expressing human Aβ, treatment with this fraction significantly reduced amyloid accumulation and attenuated neurodegenerative histopathological alterations. In human SH-SY5Y neuronal cultures, the metabolites improved cell viability under therapeutic, but not preventive, conditions following exposure to aggregated Aβ. The aqueous fraction also exhibited significant inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Whole-genome sequencing assigned the bioactive isolate to the genus Providencia, with comparative genomic analyses suggesting its placement within a distinct taxonomic lineage. Metabolomic profiling by LC-ESI-MS/MS revealed a diverse set of polar metabolites, including metabolites putatively annotated based on spectral matching, previously associated with neuroprotective and cholinesterase-modulating activities. Collectively, these findings demonstrate that bacterial polar metabolites can modulate key pathological features of Alzheimer's disease, supporting their relevance for mechanistic studies of Aβ toxicity and cholinergic dysfunction.

Animals↗

PubMed2026

Human Monocytic Models Reveal Genotype-Dependent Inflammatory Programs in VEXAS Syndrome.

OBJECTIVES: VEXAS syndrome is a severe X-linked autoinflammatory disorder caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1), with clinical outcomes that vary by UBA1 genotype. We aimed to elucidate genotype-specific inflammatory programs and identify potential therapeutic targets. METHODS: We conducted longitudinal deep phenotyping, including whole-blood RNA sequencing (RNA-seq) and clinical activity assessment. Peripheral blood samples were analyzed by single-cell RNA-seq. Human monocytic cell lines harboring each major UBA1 mutation (p.Met41Val, p.Met41Thr, or p.Met41Leu) were generated and subjected to transcriptomic and functional analyses. RESULTS: Thirteen patients with VEXAS syndrome contributed a total of 79 RNA-seq samples. Among genes upregulated in VEXAS syndrome, RNASE1 showed the strongest correlation with longitudinal disease activity (r = 0.70, FDR < 0.05) and was upregulated in patients' monocytes. In UBA1-mutant monocytic cell lines, genotype-dependent ubiquitination defects were observed in a graded manner (p.Met41Val > p.Met41Thr > p.Met41Leu), even in the absence of exogenous stimuli. These defects were accompanied by unfolded protein response activation, increased pro-inflammatory cytokine production, progressive cell death, and RNASE1 upregulation, all following the same graded pattern, recapitulating patient genotype-phenotype associations. Transcriptomic analyses demonstrated enrichment of pro-inflammatory, interferon, and necroptosis signatures in more severe genotypes. Notably, inhibition of receptor-interacting protein kinase 3 (RIPK3) markedly attenuated all pathological features, including RNASE1 upregulation. CONCLUSIONS: Our UBA1-mutant monocytic cell-line models, representing three distinct genotypes, recapitulate genotype-dependent inflammatory phenotypes that can be modulated by RIPK3 inhibition, providing a translational platform for mechanistic investigation and precision therapy development in VEXAS syndrome.

Journal Article↗

PubMed2026

Variations in carbapenem resistance associated with the VIM-1 metallo-β-lactamase across the Enterobacterales.

The VIM-1 metallo-β-lactamase enzyme, encoded within class 1 integrons, is found in Gram-negative clinical isolates worldwide and has been linked to outbreaks of bacterial pathogens in nosocomial settings. Six vim-1+ clinical isolates, from the genera Escherichia, Klebsiella and Enterobacter, were obtained from Kingston, Ontario, Canada. Whole-genome sequencing revealed that vim-1 was plasmid-borne in all strains and situated as the first gene in In916 or In110 integrons. Analysis of related plasmids suggested that these vim-1-containing plasmids are globally disseminated and have spread via horizontal gene transfer and autochthonous vertical spread within Ontario. Interestingly, the MICs of ertapenem and meropenem, two clinically relevant carbapenem antibiotics, against these six isolates varied more than tenfold, suggesting that the effects of VIM-1 are dependent on the genomic content of the host microbe. Introducing vim-1 into three common Enterobacterales laboratory strains was not sufficient to confer resistance to ertapenem and meropenem. Instead, adaptive laboratory evolution of the vim-1 + laboratory strains revealed that vim-1-mediated carbapenem resistance in these strains was dependent on epistatic interactions with ompC mutations, likely due to decreased outer membrane permeability to these antibiotics. Together, these results provide additional support for the role of gene epistasis in modulating the antimicrobial resistance phenotypes of acquired resistance genes, as well as previous results suggesting that the presence of a β-lactamase gene is insufficient to confer strong resistance to carbapenems without being paired with reduced outer membrane permeability.

beta-Lactamases↗

PubMed2025

Genetic effects on chromatin accessibility reveal the molecular mechanisms of complex traits in maize.

Cis-regulatory elements (CREs) are critical for modulating gene expression and phenotypic diversity in maize. While genome-wide association study (GWAS) hits and expression quantitative trait loci (eQTLs) are often enriched in CREs, their molecular mechanisms remain poorly understood. Characterizing CREs within accessible chromatin regions (ACRs) offers a powerful approach to link noncoding variants to chromatin structure alterations and phenotypic variation. Here, we generated ATAC-seq profiles from seedling leaves of 214 maize inbred lines, identifying 82 174 consensus ACRs. Notably, 39.55% of these ACRs exhibited significant population-wide chromatin accessibility variation. By mapping chromatin accessibility quantitative trait loci (caQTLs), we discovered 27 004 loci, including 1398 predicted to disrupt transcription factor (TF)-binding sites. Integration with multi-omics data revealed 7405 caACR-target gene pairs and linked 56 caACRs to GWAS signals for 51 agronomic traits, with significant enrichment in flowering-related pathways. Functional candidates such as ZmZIM30 - putatively regulated by caACRs - emerged as key regulators of flowering time. At the fad7 locus associated with linolenic acid content, allelic variants overlapping a caQTL showed differential chromatin accessibility. Our study provides a high-resolution cis-elements of maize leaves, deciphers the genetic basis of chromatin accessibility variation, and bridges noncoding caQTLs to molecular mechanisms underlying GWAS hits.

Zea mays↗

PubMed2026

Integrative pan-cancer analysis of transferrin reveals context-dependent prognostic associations and links to immune and metabolic disease-related programs.

BACKGROUND: Iron metabolism is closely linked to tumor biology, yet the pan-cancer significance of transferrin (TF), the major circulating iron-transport protein, remains insufficiently defined. Although TF has been implicated in cancer-related processes, its prognostic relevance, immune associations, and broader disease-related transcriptional context have not been systematically characterized across tumor types. OBJECTIVE: This study aimed to perform an integrative pan-cancer analysis of TF to characterize its expression patterns, clinical associations, immune context, pathway features, and pharmacogenomic correlations, and to explore whether TF-related signals extend to selected metabolic and chronic organ injury settings. METHODS: We used multiple public databases, including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), and Cancer Cell Line Encyclopedia (CCLE), to integrate transcriptomic, proteomic, and clinical data across 33 tumor types and selected non-malignant conditions. TF expression was evaluated across normal tissues, tumors, and cell lines, followed by survival analysis, immune infiltration analysis, TMB/MSI and methylation assessment, pathway enrichment, and drug-response correlation. Independent GEO cohorts of non-alcoholic steatohepatitis (NASH), heart failure (HF), and liver cirrhosis (LC) were used for cross-disease extension. Selected findings were further explored in OA/PA-treated hepatocytes, 786-O renal carcinoma cells, and AC16 cardiomyocytes. RESULTS: TF showed pronounced tissue specificity and cancer-type-dependent dysregulation. Across pan-cancer cohorts, the most consistent adverse survival associations were observed in kidney renal clear cell carcinoma (KIRC) and stomach adenocarcinoma (STAD), where TF remained associated with overall survival (OS) in multivariable analyses. TF expression was also correlated with cancer-type-specific immune infiltration patterns and selected drug-response profiles. Across independent NASH, HF, and LC datasets, TF expression was elevated and TF-associated pathways partially overlapped with those observed in cancer. In vitro experiments provided preliminary support that TF modulation is associated with proliferative phenotypes in KIRC cells and stress- and metabolism-related phenotypes in hepatocyte and cardiomyocyte models. CONCLUSION: These findings support TF as a context-dependent biomarker candidate in cancer, with the most consistent prognostic relevance observed in KIRC and STAD. Rather than establishing a unified mechanism across diseases, this study provides an integrative framework suggesting that TF is associated with malignant behavior, immune context, and selected metabolic stress-related programs, and warrants further mechanistic investigation.

Iron metabolism↗

PubMed2024

Polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA) are associated with the PI3K-AKT pathway activation.

AIMS: We aimed to elucidate the mechanism leading to polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA). BACKGROUND: PCOS is an endocrine disorder. Patients with RSA also have a high incidence rate of PCOS, implying that PCOS and RSA may share the same pathological mechanism. OBJECTIVE: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) and RSA GSE113790 and GSE178535) were downloaded from the Gene Expression Omnibus (GEO) database. METHODS: Datasets of PSCO and RSA patients were retrieved from the Gene Expression Omnibus (GEO) database. The "WGCNA" package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the "DAVID" database. The GSEA analysis was performed in "clusterProfiler" package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level. Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. RESULTS: The modules related to PCOS and RSA were sectioned by weighted gene co-expression network analysis (WGCNA) and positive correlation modules of PCOS and RSA were all enriched in angiogenesis and Wnt pathways. The GSEA further revealed that these biological processes of angiogenesis, Wnt and regulation of cell cycle were significantly positively correlated with the PCOS and RSA phenotypes. The intersection of the positive correlation modules of PCOS and RSA contained 80 key genes, which were mainly enriched in kinase-related signal pathways and were significant high-expressed in the disease samples. Subsequently, visualization of these genes including PDGFC, GHR, PRLR and ITGA3 showed that these genes were associated with the PI3K-AKT signal pathway. Moreover, the experimental results showed that PRLR had a higher expression in KGN cells, and that knocking PRLR down suppressed cell viability and promoted apoptosis of KGN cells. CONCLUSION: This study revealed the common pathological mechanisms between PCOS and RSA and explored the role of the PI3K-AKT signaling pathway in the two diseases, providing a new direction for the clinical treatment of PCOS and RSA.

Humans↗

PubMed2026

CRISPR/Cas9 loss-of-function screen in a neuronal model of AP-4 deficiency identifies ATG9A trafficking modulators.

Biallelic loss-of-function variants in adaptor protein complex 4 (AP-4) disrupt trafficking of transmembrane proteins at the trans-Golgi network, including autophagy-related protein 9A (ATG9A), leading to childhood-onset hereditary spastic paraplegia (AP-4-HSP). AP-4-HSP is characterized by features of both a neurodevelopmental and a degenerative neurological disease. To investigate the molecular mechanisms underlying AP-4-HSP and identify potential therapeutic targets, we conducted an arrayed CRISPR/Cas9 loss-of-function screen of 8,478 genes, targeting the "druggable genome," in a human neuronal model of AP-4 deficiency. Through this phenotypic screen and subsequent experiments, key modulators of ATG9A trafficking were identified, and complementary pathway analyses provided insights into the regulatory landscape of ATG9A transport. Knockdown of ANPEP and NPM1 enhanced ATG9A availability outside the trans-Golgi network, suggesting that they regulate ATG9A localization. These findings deepen our understanding of ATG9A trafficking in the context of AP-4 deficiency and offer a framework for the development of targeted interventions for AP-4-HSP.

Humans↗

PubMed2026

Mapping convergent regulators of melanoma drug resistance by PerturbFate.

High-throughput genomic studies have uncovered associations between diverse genetic alterations and disease phenotypes. However, elucidating how perturbations in functionally disparate genes give rise to convergent cellular states remains challenging. Here we present PerturbFate, a high-throughput, cost-effective, combinatorial-indexing single-cell platform that enables systematic interrogation of massively parallel CRISPR interference1 perturbations across the full spectrum of gene regulation, from chromatin remodelling and nascent transcription to steady-state transcriptomic phenotypes. Using PerturbFate, we profiled more than 300,000 cultured melanoma cells to characterize multimodal phenotypic and gene regulatory responses to perturbations in more than 140 vemurafenib resistance-associated genes. We uncovered a shared dedifferentiated cell state marked by convergent cooperative transcription factor activities across diverse genetic perturbations. We further dissected phenotypic responses to perturbations in Mediator complex components, linking module-specific biochemical properties to convergent transcriptional activations. We identified common regulatory nodes that drive similar phenotypic outcomes across distinct genetic perturbations. We also delineated how perturbations in functionally unrelated genes reshape cell state. Thus, PerturbFate establishes a versatile platform for identifying key molecular regulators by anchoring multimodal regulatory dynamics to disease-relevant phenotypes.

Humans↗

PubMed2025

Stress-induced altered expression of hippocampal nuclear and mitochondrial encoded genes in rats and cross-species genetic associations reveal molecular links to depression.

BACKGROUND: Mitochondria play a pivotal role in energy production, and their dysfunction not only hampers cells' ability to meet energy requirements but also contributes to the impairment of neural plasticity, a critical feature of depressive disorders. In this study, mitochondrial cross-omics analysis was carried out in the hippocampus of restraint rats to understand the role of mitochondria in depression pathophysiology. METHODS: The expression profiles of hippocampal mitochondrial and nuclear-encoded genes in mitochondrial fractions from restraint and handled control rats were obtained using high-throughput RNA sequencing. Weighted gene co-expression network analysis (WGCNA) was used to identify the gene co-expression and pathways associated with the restraint phenotype. Mutual Information Network algorithm tools Arance, CLR, and MRNET were additionally used to screen the functional modules and hub genes and their similarity with the WGCNA-based network analysis. Finally, cross-species homology followed by gene association analysis was conducted to obtain SNPs and haplotypes related to depression phenotype. RESULTS: A significant proportion of mitochondrial and nuclear-encoded genes showed differential regulation in the hippocampus of restraint rats. WGCNA and Mutual Information Network analysis yielded distinct functional modules significantly related to restraint phenotype. Further network analysis revealed distinct co-expression patterns associated with differentially expressed genes associated with these modules. Cross-species analysis showed 39 significantly associated SNPs with the depression phenotype, where the most significant SNP, rs10899570, was located within the TENM4 gene. Further, rs1573529 and rs10899570 were distributed into the linkage disequilibrium block where SNPs were highly correlated. Subsequent haplotype analysis showed that rs1573529 and rs10899570 were significantly associated with depressive behavior. CONCLUSIONS: The study demonstrates a significant impact of restraint stress on mitochondrial functions and genetic association, suggesting their critical role in depression pathophysiology.

Animals↗

PubMed2025

Multi-Omics insights into OsZFP252-OsGA20ox5 mediated drought tolerance in rice through stomatal and vascular regulation.

Rice growth is highly dependent on water availability, and drought stress significantly impacts its entire life cycle. However, previous studies lack systematic investigations into drought-responsive candidate genes across the full life cycle of rice. This study integrates transcriptomic and phenotypic data from two rice lines, IR64 (drought-sensitive) and DK151 (drought-tolerant), under varied environmental conditions at distinct growth stages. Using k-means clustering, 13 369 genes were categorized into 17 distinct expression patterns, revealing drought-responsive genes specifically upregulated or downregulated under drought stress. Weighted co-expression network analysis (WGCNA) further identified four gene modules strongly correlated with drought-related phenotypes, co-localizing 2859 drought-responsive genes through both approaches. Proteomics and metabolomics were supplemented at the booting stage, where phenotypic and transcriptomic differences under drought were most pronounced. Integrated omics results demonstrate gibberellin (GA) and abscisic acid (ABA) pathways play a key role during drought tolerance in rice, and 79 high-confidence drought-resistant candidate genes were prioritized from the 2859 drought-responsive genes. Among these, Gibberellin 20-oxidase 5 (OsGA20ox5) was identified as a key negative regulator of drought tolerance. Furthermore, the transcription factor zinc finger protein 252 (OsZFP252) directly binds to the OsGA20ox5 promoter, repressing its expression and enhancing ABA biosynthesis, thereby improving drought tolerance by increasing stomatal closure and expanding vascular bundle water transport capacity. Notably, the drought-tolerant haplotype 2-4 (Hap2-4) of OsGA20ox5 provides valuable insights for drought-resistant breeding.

Oryza↗

PubMed2026

Sex-specific ethylene responses drive floral sexual plasticity in Cannabis sativa.

Cannabis sativa L. exhibits pronounced sexual plasticity in which both XX and XY plants can undergo floral phenotypic sex reversal in response to ethylene modulation, yet the underlying molecular mechanisms remain poorly defined. Here, we present the most extensive multi-omic analysis of ethylene-induced sex change in C. sativa to date, integrating over 130 RNA-seq libraries, ethylene pathway metabolite quantification, and whole-genome sequencing across three XX and XY genotypes. Treatments with silver thiosulfate and ethephon induced more than 80% phenotypic conversion, but transcriptomic responses diverged sharply between XX and XY plants. Profiling 47 ERGs revealed 14 high-confidence candidates, including CsACS1, CsACO5, CsERF1, and CsMTN, with sex-specific and temporal expression patterns that show dynamic ethylene mediation of plasticity. Early transcriptional activation occurred prior to the emergence of flowers, within 18 h of sex-change treatments and the photoperiod-induced transition to flowering. As opposite-sex floral tissues emerged, ethylene-related gene expression shifted accordingly within developing floral organs, with distinct sets of genes stabilizing the opposite-sex phenotype in XX and XY plants. Several candidates were located in non-recombining regions of the X chromosome or were absent from the Y chromosome, and most exhibited low nucleotide diversity, consistent with functional constraint. These results provide a high-resolution view of ethylene-responsive sexual plasticity in cannabis and show that the shared capacity for sex reversal in XX and XY plants is implemented through distinct regulatory trajectories that produce opposite-sex floral phenotypes. This work expands the mechanistic understanding of sex expression in dioecious species and identifies candidate genes relevant to the development of sex-stable cultivars.

Ethylenes↗

PubMed2025

Multi-omics reveals an ecdysone-activated Eip75B-FABP signaling axis coordinating nutrient metabolism for development in Hermetia illucens.

INTRODUCTION: Efficient nutrient storage is essential for insect development and energy homeostasis; however, the mechanisms coordinating nutrient allocation during ontogeny are not well understood. Elucidating these systems may yield valuable insights to insect metabolic adaptation. OBJECTIVES: This study aimed to identify regulatory modules governing nutrient metabolism in insects, focusing on hormonal and metabolic interplay. METHODS: Multi-omics profiling (proteomics, phosphoproteomics, and transcriptomics) was conducted throughout the life cycle, from egg to adult, to identify metabolic regulators. RNAi was utilized for gene knockdown, followed by qRT-PCR and mitochondrial DNA quantification to evaluate knockdown efficiency and its metabolic implications. Assessments of nutrient metabolism were performed using assays for triglycerides, crude protein, and fatty acid synthase. EMSA and BODIPY staining examined transcriptional regulation and lipid droplet dynamics. RESULTS: Utilizing an integrative multi-omics approach, this study elucidates the temporal metabolic regulators in insects. A conserved regulatory module was identified in which the PPAR homolog, ecdysone-induced protein 75B (Eip75B), functions as a transcriptional activator of fatty acid binding protein (FABP), sustaining lipid metabolic homeostasis during the larval stage. PPARγ modulators (rosiglitazone and GW9662) alter lipid accumulation, along with the expression of Eip75B and FABP, which was measured by qRT-PCR. Furthermore, the deficiency of FABP may reprogram metabolic pathways by inhibiting lipid storage and promoting mitochondrial β-oxidation, as supported by increased mitochondrial DNA copy number, as well as enhancing protein synthesis. This metabolic change could be modulated by ecdysone signaling, as hormonal supplementation effectively rescued the lipid loss phenotype. Our results establish the ecdysone-Eip75B-FABP signaling axis as a central regulatory module that integrates hormonal and nutrient-sensing signals to control insect nutritional metabolism. CONCLUSION: The ecdysone-Eip75B-FABP axis integrates hormonal and nutrient signals to regulate metabolic plasticity, underscoring a universal strategy for developmental energy allocation. The data also offer potential implications for research on metabolic disorders and bioenergy applications.

Animals↗

PubMed2026

Associations between gut microbiota on carcass traits and meat quality in Neijiang pigs, Yorkshire pigs, and their hybrids.

This study was designed as an exploratory analysis to compare carcass performance, meat quality traits, and gut microbiota of Neijiang pigs (NN), Yorkshire pigs (YY), and Yorkshire × Neijiang hybrid pigs (YN), with the goal of generating testable hypotheses regarding potential links between gut microbial composition and production phenotypes. Compared with NN pigs, YN hybrids exhibited improved carcass performance while inheriting the favorable meat quality characteristics of Neijiang pigs. The results of 16S rRNA sequencing analysis showed that the relative abundance of the microbiota was similar to that of NN pigs. LDA effect size (LEfSe) results showed that Streptococcus, Treponema, probable_genus_10 and Fibrobacter were the differentially enriched taxa in YN pigs (p < 0.05). Correlation analysis was performed on carcass, meat quality and intestinal microbiota screened out by LEfSe. The results showed that Akkermansia tended to positively associate with body length and oblique length in YN pigs; Dialister correlated positively with dressing rate and pH45min; Treponema showed positive trends with a*45min and a*24h (p < 0.05). Finally, the correlation network model preliminarily mapped associations among production traits, gut microbiota, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for exploratory screening. Nine core microbial taxa exhibited close correlations with phenotypic indicators, which implied that these microbes might modulate metabolic pathways to shape pig performance. Overall, hybrids inherited superior parental carcass and meat quality but harbored unique gut microbial communities relative to purebreds-these preliminary correlative observations generate new hypotheses that gut microbiota may contribute to heterosis-associated phenotypic advantages, which require further targeted validation.

Animals↗

PubMed2026

Evaluation of Oxford nanopore sequencing for antimicrobial resistance surveillance in Salmonella: comparison with phenotypic antimicrobial susceptibility in a large-scale study.

UNLABELLED: Salmonella is a major zoonotic foodborne pathogen, and antimicrobial resistance (AMR) in Salmonella presents a significant public health challenge. Compared with conventional antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS) provides a more rapid and comprehensive approach to AMR characterization, thereby informing antimicrobial selection and supporting public health surveillance. In this study, Oxford Nanopore Technology (ONT)-based WGS was performed on 1,490 Salmonella isolates collected through nationwide surveillance in Taiwan in 2025. Genotypic resistance inferred from WGS data was compared with phenotypic AST results to assess the performance of ONT-WGS. Overall, WGS-inferred resistance showed high concordance with phenotypic resistance for most antimicrobials. However, major genotype-phenotype discordance was observed, attributed to four categories: (i) breakpoint-dependent classification, (ii) reduced or absent phenotypic expression of resistance genes, (iii) minimum inhibitory concentration (MIC) modulation by ramAp, and (iv) absence of known AMR determinants. Notable discrepancies included tigecycline resistance without known genetic determinants, nalidixic acid resistance linked to ramAp-mediated MIC elevation, and a high prevalence of colistin resistance (35.7%) in S. Enteritidis, with most resistant isolates lacking identifiable AMR determinants. Additionally, a significant proportion of ESBL- and AmpC-producing isolates were classified as susceptible or intermediate to cefotaxime and ceftazidime under CLSI criteria, highlighting the potential for misclassification and treatment failure. These findings demonstrate that ONT-WGS enables accurate and comprehensive AMR characterization by directly identifying resistance determinants and avoiding potential misclassification associated with breakpoint-based AST interpretations. When interpreted appropriately, WGS can support better antimicrobial selection and serve as a valuable alternative to conventional susceptibility testing. IMPORTANCE: Accurate prediction of antimicrobial resistance is essential for appropriate therapy and effective surveillance of Salmonella. However, discordance between genotype-based predictions and phenotypic antimicrobial susceptibility testing (AST) can complicate clinical interpretation. In this nationwide study of 1,490 Salmonella isolates, we show that Oxford Nanopore Technology-based whole-genome sequencing (ONT-WGS) provides rapid and comprehensive detection of antimicrobial resistance determinants with high concordance to phenotypic AST. We further identify four major mechanisms underlying genotype-phenotype discordance, including breakpoint-dependent classification, reduced or absent phenotypic expression of resistance genes, minimum inhibitory concentration (MIC) modulation by ramAp, and the absence of known AMR determinants. These findings demonstrate how WGS can complement conventional AST, improve interpretation of challenging susceptibility results, and strengthen genomic surveillance of emerging antimicrobial-resistant Salmonella.

Microbial Sensitivity Tests↗

PubMed2026

Retrotransposable element derepression distinguishes DNMT3A-mutant from TET2-mutant clonal haematopoiesis.

Clonal haematopoiesis (CH) is driven by somatic mutations in haematopoietic stem cells that generate clonal populations detectable in peripheral blood and is present in 10-20% of individuals over the age of 65. Mutations in DNMT3A and TET2 are the most common drivers and have been linked to inflammatory phenotypes and increased risk of haematologic and cardiovascular disease. However, the cell-intrinsic mechanisms connecting these mutations to inflammatory signalling remain incompletely understood. Because retrotransposable elements (RTEs) are epigenetically regulated and can activate innate immune pathways when derepressed, we hypothesised that RTE reactivation may represent a mutation-specific mechanism linking clonal haematopoiesis driver mutations to inflammatory pathways. We analysed RTE expression and clonal burden in peripheral blood mononuclear cell (PBMC) samples from 56 individuals with CH and 12 non-CH controls using integrated genomic and transcriptomic approaches, with complementary validation by TARGET-seq across haematopoietic lineages. High variant allele frequency (VAF; > 10%) DNMT3A-mutant clones exhibited widespread derepression of RTEs, particularly LINE and LTR families, whereas TET2-mutant clones showed a trend towards reduced RTE expression relative to controls. Transcriptomic analyses revealed that DNMT3A high-variant allele frequency clones with elevated RTE expression were enriched for inflammatory signalling pathways, including TNF-α/NF-κB signalling, interferon responses, and senescence-associated signatures. In contrast, TET2-mutant clones lacked these RTE-associated inflammatory signatures and instead showed enrichment of oxidative phosphorylation, reactive oxygen species signalling, and a mechanistic target of rapamycin complex 1 pathway. These findings were reproduced in an independent cohort. Collectively, our results highlight mutation-specific inflammatory mechanisms in clonal haematopoiesis and provide a foundation for future functional and preclinical studies to determine whether modulation of RTE activity can influence the inflammatory phenotype of DNMT3A-mutant CH and represent a potential therapeutic strategy.

DNMT3A↗

PubMed2026

Bacterial Outer Membrane Vesicles in Colorectal Cancer: Interdomain Communication Hubs in Pathogenesis and Immunotherapy.

The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs)-nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms-have emerged as critical long-range signaling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift toward exploiting next-generation probiotic and engineered OMVs as highly tunable therapeutic platforms. By combining cutting-edge bioengineering strategies-such as biomimetic mineralization to neutralize local tissue acidity and chemotherapeutic packaging-these nanovectors effectively reprogram the immunosuppressive tumor microenvironment (TME). Specifically, optimized OMVs modulate macrophage polarization from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically "cold" tumors "hot." Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.

Colon cancer↗