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PubMed2026

LLPS-based classification and a novel prognostic signature reveal NRF1 as a therapeutic target in pancreatic cancer.

BACKGROUND: Aberrant liquid-liquid phase separation (LLPS) can alter biomolecular condensate functions and may influence pancreatic tumorigenesis and progression, but the specific role of LLPS regulators in prognosis and the tumor immune microenvironment (TIME) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: We integrated transcriptome data of LLPS regulator-related differentially expressed genes (DEGs; n = 298) in a cohort of 176 PDAC patients from TCGA. Three LLPS regulator subtypes (LS1-LS3) were identified through multi-omics analyses, and a prognostic LLPS subtype-related risk model (LRRPC) was developed and validated. Chromatin immunoprecipitation confirmed NRF1 binding to promoters of key risk genes, and in vitro and in vivo experiments assessed the effects of NRF1 targeting on tumor growth. RESULTS: The three LLPS regulator subtypes exhibited significant differences in prognosis, clinical features, genomic alterations, TIME patterns and predicted immunotherapy response. The LRRPC signature predicted prognosis and immunotherapy efficacy across cohorts and was associated with tumor biomarkers and immune infiltration. Nuclear Respiratory Factor 1 (NRF1) directly regulated hub genes such as FAM83A, RHOV and ITGB6, promoting PDAC cell proliferation, while its inhibition induced apoptosis and reduced tumor growth. CONCLUSIONS: This study proposes an LLPS-based stratification framework for PDAC, and the LRRPC model provides an LLPS subtype-related risk score that may assist personalized prognostic assessment and immunotherapy stratification. NRF1 emerges as a promising therapeutic candidate whose targeting can inhibit tumor progression in PDAC experimental models and warrants further evaluation.

Immunotherapy↗

PubMed2025

USP7 Inhibitors Destabilize EBNA1 and Suppress Epstein-Barr Virus Tumorigenesis.

Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt's lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7). Here, we show that pharmacological inhibitors and small interfering RNA (siRNA) targeting USP7 reduce EBNA1 protein levels in a proteosome-dependent manner. Proteomic analysis revealed that USP7 inhibitor GNE6776 altered the EBNA1 protein interactome, including disrupting USP7 association with EBNA1. GNE6776 also inhibited EBNA1 binding to EBV oriP DNA and reduced viral episome copy number. Transcriptomic studies revealed that USP7 inhibition affected chromosome segregation and mitotic cell division pathways in EBV+ cells. Finally, we show that GNE6776 selectively inhibited EBV+ gastric and lymphoid cell proliferation in cell culture and slowed EBV+ tumor growth in mouse xenograft models. These findings suggest that USP7 inhibitors perturb EBNA1 stability and function and may be exploited to treat EBV latent infection and tumorigenesis.

Ubiquitin-Specific Peptidase 7↗

PubMed2026

Snail immunity to schistosomes: insights from omics studies.

Schistosomiasis is a serious public health concern, with transmission facilitated by a small number of freshwater snail intermediate host species. Infection outcomes vary greatly across the primary vector genera, Biomphalaria (for Schistosoma mansoni), Bulinus (for S. haematobium), and Oncomelania (for S. japonicum), even within species, ranging from full resistance to high compatibility. Omics methods have altered this field by correlating host genotype, baseline immunological status, and time-resolved responses to whether invading miracidia are eliminated or develop sporocysts. Evidence from genomes, transcriptomics, proteomics, and epigenomics suggests that resistance is frequently primed prior to exposure. However, the clearest divergence between resistant and susceptible trajectories occurs during a small early window (<12-48 h) after penetration. During this time, recognition, hemocyte recruitment, and soluble effector deployment either come together quickly or are delayed and guided by parasite-derived modulators. Established infections cause the host to adapt to chronic conditions through immune regulation, metabolic reprogramming, tissue and neuroendocrine remodeling, microbiome modification, and parasite castration. Comparative genomics reveals that each vector genus has evolved its own immunogenomic profile, which includes lineage-specific expansions of recognition and effector gene families. Together, these findings can help with field surveillance and intervention by providing molecular compatibility markers, functional tools for testing candidate genes, and tactics that target parasite-derived immune modulators. Integrated multi-omics approaches are a top priority, yet they are still limited in snail vectors compared to other disease vector systems.

Animals↗

PubMed2025

O-GlcNAcylation of nuclear proteins in the mouse liver exhibit daily oscillations that are influenced by meal timing.

The liver circadian clock and hepatic transcriptome are highly responsive to metabolic signals generated from feeding-fasting rhythm. Previous studies have identified a number of nutrient-sensitive signaling pathways that could interpret metabolic input to regulate rhythmic hepatic biology. Here, we investigated the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) in mediating metabolic regulation of rhythmic biology in the liver. We observe daily oscillation of global nuclear protein O-GlcNAcylation in the liver of mice subjected to night-restricted feeding (NRF) using label-free global O-GlcNAc proteomics. Additional site-specific O-GlcNAc analysis by tandem mass tag mass spectrometry further supports temporal differences in O-GlcNAcylation by revealing day-night differences. Proteins involved in gene expression are enriched among rhythmically O-GlcNAcylated proteins, suggesting rhythmic O-GlcNAcylation may directly regulate the hepatic transcriptome. We show that rhythmic O-GlcNAcylation can also indirectly modulate nuclear proteins by interacting with phosphorylation. Several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. Specifically, we show that O-GlcNAcylation occurs at a phospho-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), thus regulating its stability and transcriptional output. Finally, we report that day-restricted feeding (DRF) in the nocturnal mouse significantly alters O-GlcNAcylation pattern. Whereas global O-GlcNAcylation analysis indicates dampening of global O-GlcNAcylation rhythm in mice fed under DRF, site-specific analysis reveals differential responses of O-GlcNAc sites when timing of food intake is altered. Notably, a substantial number of O-GlcNAcylation sites exhibit inverted day-night profiles when mice are subjected to DRF. This suggests the dysregulation of daily nuclear protein O-GlcNAcylation rhythm may contribute to the disruption in liver transcriptome previously observed in DRF condition. In summary, our results provide new mechanistic insights into metabolic regulation of hepatic transcriptional regulators via interplay between O-GlcNAcylation and phosphorylation and shed light on the deleterious effects of improper mealtimes.

Animals↗

PubMed2026

Chronic ethanol exposure alters the expression of genes associated with GPCR-related signaling in the olfactory bulb of male mice.

Chronic ethanol exposure, a key feature of alcohol use disorder (AUD), can affect the nervous system, but its molecular impact on the olfactory bulb remains unclear. In this study, an intermittent two-bottle voluntary drinking model was established in male mice, and transcriptome sequencing was performed on olfactory bulb tissues. DESeq2 analysis identified 188 differentially expressed genes, including 68 upregulated and 120 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway database (Reactome) analyses indicated that ethanol-responsive genes were predominantly enriched in receptor-mediated signaling pathways, particularly those linked to G protein-coupled receptor (GPCR) signaling. Protein-protein interaction analysis further identified eight core GPCR-related genes. Quantitative real-time PCR (qRT-PCR) validation revealed that Cxcl10, Grp, Pcp2, and Pdyn were markedly downregulated in the ethanol group. These results suggest that chronic ethanol exposure is associated with transcriptional alterations in the male mouse olfactory bulb and may selectively affect several GPCR-related signaling components. This study provides candidate molecular evidence for further investigation of ethanol-associated olfactory dysfunction.

Chronic ethanol exposure↗

PubMed2026

TNFα-induced endothelial extracellular vesicles regulate astrocyte function: an integrated transcriptomic and proteomic study.

Endothelial cells and astrocytes are critical structural and functional components of the blood-brain barrier. In many neuroinflammatory diseases, endothelial cells are among the first to respond to inflammatory stimuli and release extracellular vesicles (EVs). However, whether inflammatory stimulation alters EV RNA cargo and subsequently regulates astrocyte function remains unclear. In this study, we performed integrated RNA sequencing and proteomic analyses to investigate the effects of TNFα-stimulated endothelial EVs on astrocytes. RNA profiling revealed significant alterations in EV cargo after TNFα stimulation, including 867 upregulated and 577 downregulated mRNAs, 317 upregulated and 15 downregulated lncRNAs, and 88 upregulated and 62 downregulated miRNAs. The results of functional enrichment analysis suggested that altered EV RNAs may primarily promote inflammatory responses, cell migration, and RNA splicing in astrocytes while reducing their regulatory effects on neuronal projection and calcium homeostasis. Further integrative analysis of EV RNAs and astrocytic proteomics revealed key overlapping targets, including upregulated expression of ICAM1, SOD2, TFPI2, and TNFAIP8, whereas NFKBIA expression was consistently decreased. Network analysis revealed NF-κB as the central regulatory node. Reduced levels of EV-derived NFKBIA mRNA were associated with decreased IκBα protein levels in astrocytes, which promoted NF-κB activation and inflammatory cytokine release. Finally, overexpression of IκBα in astrocytes significantly attenuated TNFα EV-induced IL-1β and IL-6 secretion. Collectively, these findings demonstrate that TNFα-stimulated endothelial EVs coordinately regulate astrocyte function through mRNA, lncRNA, and miRNA cargo and that the IκBα/NF-κB axis may be a key mechanism underlying endothelial EV-mediated inflammatory disruption of the blood-brain barrier.

Astrocytes↗

PubMed2026

De novo chromatin remodelling variants in sporadic Chiari 1 malformation.

Chiari 1 malformation (CM1) is the most common congenital malformation of the human hindbrain. Although prior studies have implicated chromatin-remodeling genes in CM1, the de novo genetic architecture and underlying neurodevelopmental mechanisms remain incompletely defined. To investigate the molecular genetics of a novel familial form of CM1 linked with syringomyelia and tethered cord and determine whether rare, damaging de novo variants (DNVs) contribute to sporadic CM1 risk with gene- and pathway-level resolution, we performed whole-exome sequencing in an ultra-rare multigenerational family with CM1 and associated spinal pathology, and in the largest assembled trio-based cohort to date, comprising 1,585 proband-parent trios with sporadic, idiopathic CM1 (2017-2025). The comparison cohort included 1,798 unaffected control siblings. Clinical phenotyping was by systematic medical record review. Structural domain mapping, in silico modeling, and integration with single-cell transcriptomic data from developing human cerebellum was conducted to assess biological plausibility. A heterozygous loss-of-function variant in CHD3 segregated with CM1 and syringomyelia in a multigenerational family. In the trio-based cohort, rare protein-altering DNVs were significantly enriched across multiple chromodomain helicase DNA-binding (CHD) genes, including CHD1, CHD3, CHD4, and CHD8, exceeding gene-specific mutation expectations (protein-damaging variants: P = 1.3 × 10-9; predicted loss-of-function variants: P = 8.6 × 10-5). CHD1 contained two pathogenic DNVs (p.A999D and p.E984K). CHD4 (p.D744N, p.T1813P, and p.I1102T) and CHD8 (p.R1402X, p.R1472X, and p.R2035X) each contained three new DNVs. Variants clustered within conserved ATPase, helicase, and chromodomain regions essential for chromatin remodeling, and these patients frequently had comorbid developmental delay and related neurodevelopmental features. Single-cell transcriptomic analyses demonstrated enrichment in Purkinje cells and inhibitory neurons of midgestational cerebellum, where CHD gene products form a coherent chromatin-regulatory network. Rare, large-effect DNVs that disrupt chromatin-remodeling programs contribute to sporadic CM1, implicating genetically encoded dysregulation of cerebellar development as a central disease mechanism. Exome sequencing may complement surgical evaluation of children with sporadic CM1, particularly when accompanied by neurodevelopmental concerns, informing prognosis and family counseling.

de novo variants↗

PubMed2026

Molecular and Immune Landscape of Recurrent and/or Distant Metastatic Squamous Cell Carcinoma of the Head and Neck: An EORTC/IMMUCAN Project.

PURPOSE: Recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is a heterogeneous clinical entity with a poor prognosis. The molecular and immune landscape of R/M SCCHN is underexplored. To offer a comprehensive view of the tumor microenvironment and molecular profile of R/M SCCHN, we performed an in-depth molecular and immune characterization, evaluating the impact of human papillomavirus (HPV) status, tobacco and alcohol history, primary tumor site, relapse pattern, and treatment history at the genomic, transcriptomic, and immune levels. EXPERIMENTAL DESIGN: We analyzed 253 R/M SCCHN fresh tumor biopsies from the IMMUcan project using RNA sequencing (RNA-seq), whole-exome sequencing, and multiplex immunofluorescence (mIF). RESULTS: The primary clinical factor affecting the immune microenvironment was the number of treatment lines, with significant declines in T cells and B cells observed via mIF and RNA-seq as the number of R/M treatment lines progressed. IL6, IL13, IL15, and NRF2 pathways were enriched in HPV-negative R/M SCCHN compared with HPV-positive tumors, whereas no immune differences were detected between these two clinical groups. Specific genomic alterations were observed in laryngeal cancer (DDR2, FOXP1, KLF5, and ROBO2), whereas nonsmokers/nondrinkers exhibited alterations in SPEN, PBRM1, and CYLD. 11q13.3 amplification was linked to HPV-negative metastatic tumors and hypopharyngeal cancer. HPV-negative SCCHN with locoregional recurrence showed elevated EGFR and CXCL12 pathway activity. Partial epithelial-mesenchymal transition transcriptomic signatures correlated with poor survival, whereas lymphocyte infiltration, especially in the context of tertiary lymphoid structures, was associated with improved survival. CONCLUSIONS: Our study highlights key molecular and immune differences across R/M SCCHN subgroups, identifies potential biomarkers, and suggests biological rationales for tailored therapeutic strategies.

Humans↗

PubMed2026

Biocontrol efficacy of Bacillus albus SSR3 for controlling postharvest fungal pathogens and mycotoxin contamination.

Sweetpotato black rot, caused by Ceratocystis fimbriata, is a major postharvest disease that leads to substantial storage losses worldwide. In this study, a salt-tolerant rhizobacterial strain, Bacillus albus SSR3, was isolated from the rhizosphere of sweetpotato grown in saline-alkali soil, with broad-spectrum antagonistic activity against postharvest fungal pathogens. LC-MS/MS analysis revealed diverse bioactive metabolites associated with its antifungal activity. Integrated transcriptomic and metabolomic analyses showed that SSR3 bioactive metabolites extensively reprogrammed fungal metabolism, particularly pathways involved in carbohydrate and amino acid metabolism, antioxidant defense, and energy production. These alterations were accompanied by disruption of cell wall and membrane integrity, excessive reactive oxygen species accumulation, and mitochondrial dysfunction, ultimately inhibiting fungal growth. Here, we also found that SSR3 bioactive metabolites effectively inhibited aflatoxin B1 production by Aspergillus flavus and deoxynivalenol accumulation in Fusarium graminearum. In vivo assays further demonstrated that SSR3 bioactive metabolites significantly reduced sweetpotato black rot severity and effectively limited fungal colonization and mycotoxin contamination in stored agricultural commodities. Collectively, our findings demonstrate that B. albus SSR3 suppresses postharvest fungal pathogens through coordinated metabolic reprogramming, oxidative stress induction, and cellular integrity disruption, highlighting its potential as a sustainable biocontrol agent for postharvest disease management.

Bacillus albus↗

PubMed2026

Exogenous gibberellin promotes lateral branch development in stumping Pinus yunnanensis by regulating endogenous hormones and TCP genes.

While plant stumping can break apical dominance, promote lateral branching, and thereby increase yield, a significant technical challenge remains in further enhancing the coppicing regrowth capacity after stumping. This study used one-year-old Pinus yunnanensis Franch seedlings as subjects. Through exogenous application of gibberellin 3 (GA3) and Paclobutrazol (PAC), it investigated the regulatory role of gibberellin (GA) in sprouting and identified TCP genes related to branching within the GA pathway. Results indicate that exogenous hormone treatments altered endogenous hormone levels in P. yunnanensis seedlings. Exogenous GA3 treatment significantly increased endogenous IPA, ABA, GA3, GA1, SA, and SAG content. Correlation analysis with sprout number revealed a positive relationship between endogenous hormones and sprout number, indicating that exogenous GA3 significantly influenced sprout number. After hormone application, the cumulative number of sprouts increased with seedling age across all treatments. Therefore, to further investigate whether changes in sprout number were caused by gene alterations in the GA signaling pathway, this study analyzed the GA signaling pathway and its associated transcription factors. Fifteen TCP family members were screened from the P. yunnanensis transcriptome, phylogenetically classified into Class I and Class II subfamilies. Conserved motif sites within the Class II family co-occurred, exhibiting high conservation. Genes from the Class II subfamily were cloned, and their differential expression across various tissues was analyzed via real-time quantitative PCR. Expression patterns under different hormone treatments were also examined. Our results reveal that PyTCP4, PyTCP6, and PyTCP20 are significantly upregulated by PAC (a GA synthesis inhibitor) and show strong negative correlations with sprouts number, while GA3 treatment partially alleviates this effect. These findings provide direct evidence that TCP transcription factors act as repressors of shoot branching, linking their hormone-responsive expression to the regulation of sprouts formation in P. yunnanensis. These results indicate that TCP transcription factors play a crucial role in shoot and root emergence, with their expression influenced by exogenous hormones, thereby affecting the growth and development of emerging shoots and roots. This provides a reference and basis for analyzing the expression patterns and functions of TCP genes in P. yunnanensis, facilitating further research into their functions.

Gibberellins↗

PubMed2025

iSoMAs: Finding isoform expression and somatic mutation associations in human cancers.

Aberrant alternative splicing, prevalent in cancer, impacts various cancer hallmarks involving proliferation, angiogenesis, and invasion. Splicing disruption often results from somatic point mutations rewiring functional pathways to support cancer cell survival. We introduce iSoMAs (iSoform expression and somatic Mutation Association), an efficient computational pipeline leveraging principal component analysis technique, to explore how somatic mutations influence transcriptome-wide gene expression at the isoform level. Applying iSoMAs to 33 cancer types comprising 9,738 tumor samples in The Cancer Genome Atlas, we identified 908 somatically mutated genes significantly associated with altered isoform expression across three or more cancer types. Mutations linked to differential isoform expression occurred through both cis- and trans-acting mechanisms, involving well-known oncogenes/suppressor genes, RNA binding protein and splicing factor genes. With wet-lab experiments, we verified direct association between TP53 mutations and differential isoform expression in cell cycle genes. Additional iSoMAs genes have been validated in the literature with independent cohorts and/or methods. Despite the complexity of cancer, iSoMAs attains computational efficiency via dimension reduction strategy and reveals critical associations between regulatory factors and transcriptional landscapes.

Humans↗

PubMed2020

Metabolic Dysregulation of the Lysophospholipid/Autotaxin Axis in the Chromosome 9p21 Gene SNP rs10757274.

BACKGROUND: Common chromosome 9p21 single nucleotide polymorphisms (SNPs) increase coronary heart disease risk, independent of traditional lipid risk factors. However, lipids comprise large numbers of structurally related molecules not measured in traditional risk measurements, and many have inflammatory bioactivities. Here, we applied lipidomic and genomic approaches to 3 model systems to characterize lipid metabolic changes in common Chr9p21 SNPs, which confer ≈30% elevated coronary heart disease risk associated with altered expression of ANRIL, a long ncRNA. METHODS: Untargeted and targeted lipidomics was applied to plasma from NPHSII (Northwick Park Heart Study II) homozygotes for AA or GG in rs10757274, followed by correlation and network analysis. To identify candidate genes, transcriptomic data from shRNA downregulation of ANRIL in HEK-293 cells was mined. Transcriptional data from vascular smooth muscle cells differentiated from induced pluripotent stem cells of individuals with/without Chr9p21 risk, nonrisk alleles, and corresponding knockout isogenic lines were next examined. Last, an in-silico analysis of miRNAs was conducted to identify how ANRIL might control lysoPL (lysophosphospholipid)/lysoPA (lysophosphatidic acid) genes. RESULTS: Elevated risk GG correlated with reduced lysoPLs, lysoPA, and ATX (autotaxin). Five other risk SNPs did not show this phenotype. LysoPL-lysoPA interconversion was uncoupled from ATX in GG plasma, suggesting metabolic dysregulation. Significantly altered expression of several lysoPL/lysoPA metabolizing enzymes was found in HEK cells lacking ANRIL. In the vascular smooth muscle cells data set, the presence of risk alleles associated with altered expression of several lysoPL/lysoPA enzymes. Deletion of the risk locus reversed the expression of several lysoPL/lysoPA genes to nonrisk haplotype levels. Genes that were altered across both cell data sets were DGKA, MBOAT2, PLPP1, and LPL. The in-silico analysis identified 4 ANRIL-regulated miRNAs that control lysoPL genes as miR-186-3p, miR-34a-3p, miR-122-5p, and miR-34a-5p. CONCLUSIONS: A Chr9p21 risk SNP associates with complex alterations in immune-bioactive phospholipids and their metabolism. Lipid metabolites and genomic pathways associated with coronary heart disease pathogenesis in Chr9p21 and ANRIL-associated disease are demonstrated.

Chromosomes, Human, Pair 9↗

PubMed2026

SHMT2: a Metabolic and Immune Biomarker of Aggressive Lung Adenocarcinoma.

Serine/glycine-one-carbon (SGOC) metabolism is frequently altered in lung adenocarcinoma (LUAD), but its relationship to tumor behavior and predicted immunotherapy responsiveness remains incompletely defined. Metabolomic profiling of 23 paired LUAD and adjacent normal lung tissues was performed using internal extractive electrospray ionization mass spectrometry. Transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort (TCGA-LUAD) were analyzed to assess SHMT2 expression, prognosis, differentially expressed genes, and immune-related features. Predicted response to immune checkpoint blockade was evaluated using Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA), and drug sensitivity was inferred using oncoPredict. Single-cell RNA-seq data were used to examine the cellular distribution of SHMT2. Experimental validation included quantitative reverse-transcription PCR (RT-qPCR), western blotting, Human Protein Atlas (HPA) immunohistochemistry, and short hairpin RNA (shRNA)-mediated SHMT2 knockdown followed by proliferation, wound-healing and colony formation assays. Metabolomic analysis identified glycine, serine, and threonine metabolism as a prominently altered pathway in LUAD. SHMT2 was upregulated in LUAD and associated with worse overall survival and adverse clinicopathological features. SHMT2-high tumors displayed enrichment of cell-cycle and SGOC-related transcriptional programs, lower immune and stromal scores, and reduced predicted responsiveness to immunotherapy. Single-cell analysis showed relative enrichment of SHMT2 expression in B cell populations. In vitro, SHMT2 was overexpressed in LUAD cells, and its knockdown suppressed proliferation, migration, and clonogenic growth. Collectively, SHMT2 is associated with SGOC metabolic reprogramming, aggressive tumor phenotypes, and an immune-disadvantaged state in LUAD, supporting its potential relevance as a biomarker; therapeutic targeting requires additional pharmacologic and in vivo validation.

Humans↗

PubMed2025

Unveiling the mechanism of micro-and-nano plastic phytotoxicity on terrestrial plants: A comprehensive review of omics approaches.

Micro-and-nano plastics (MNPs) are pervasive in terrestrial ecosystems and represent an increasing threat to plant health; however, the mechanisms underlying their phytotoxicity remain inadequately understood. MNPs can infiltrate plants through roots or leaves, causing a range of toxic effects, including inhibiting water and nutrient uptake, reducing seed germination rates, and impeding photosynthesis, resulting in oxidative damage within the plant system. The effects of MNPs are complex and influenced by various factors including size, shape, functional groups, and concentration. Recent advancements in omics technologies such as proteomics, metabolomics, transcriptomics, and microbiomics, coupled with emerging technologies like 4D omics, phenomics, spatial transcriptomics, and single-cell omics, offer unprecedented insight into the physiological, molecular, and cellular responses of terrestrial plants to MNPs exposure. This literature review synthesizes current findings regarding MNPs-induced phytotoxicity, emphasizing alterations in gene expression, protein synthesis, metabolic pathways, and physiological disruptions as revealed through omics analyses. We summarize how MNPs interact with plant cellular structures, disrupt metabolic processes, and induce oxidative stress, ultimately affecting plant growth and productivity. Furthermore, we have identified critical knowledge gaps and proposed future research directions, highlighting the necessity for integrative omics studies to elucidate the complex pathways of MNPs toxicity in terrestrial plants. In conclusion, this review underscores the potential of omics approaches to elucidate the mechanisms of MNPs-phytotoxicity and to develop strategies for mitigating the environmental impact of MNPs on plant health.

Plants↗

PubMed2026

A pan-cancer analysis of MEX3D in human tumors.

BACKGROUND: MEX3D, a member of the MEX3 RNA-binding protein family, has emerged as a potential regulatory molecule in cancer. However, its role across different tumor types remains largely unexplored. METHODS: We conducted a pan-cancer analysis of MEX3D using transcriptomic and proteomic data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Expression patterns, clinical correlations, survival outcomes, genetic alterations, RNA modification associations, immune infiltration, and functional enrichment were systematically evaluated. RESULTS: MEX3D was significantly dysregulated in numerous cancers at both mRNA and protein levels. Its expression correlated with tumor stage in ACC, LIHC, OV, SKCM, and THCA. Elevated MEX3D expression was associated with poor overall survival (OS) and disease-specific survival (DSS) in multiple malignancies, including ACC, LGG, LUAD, and MESO. Genetic alteration analysis revealed frequent amplifications and mutations, particularly in SARC and OV. MEX3D was positively correlated with RNA modification-related genes (m1A, m5C, m6A) and immune regulatory genes such as CD276, TGFB1, VEGFA, and ICOSLG. Additionally, MEX3D expression showed significant associations with tumor mutational burden (TMB), microsatellite instability (MSI), and cancer-associated fibroblast infiltration. Functional enrichment analyses indicated that MEX3D-related genes are involved in reproductive cellular processes, RNA binding, the Hippo signaling pathway, and microRNA-related oncogenic pathways. CONCLUSION: This pan-cancer analysis highlights the heterogeneous expression and cancer-specific prognostic significance of MEX3D. MEX3D is associated with immune infiltration, immune regulatory genes, RNA modification-related genes, TMB/MSI, and pathways involved in gene regulation and tumor progression. These findings suggest that MEX3D may participate in cancer-specific post-transcriptional and microenvironmental regulatory networks.

Biomarker↗

PubMed2026

Maternal high-fat diet modulates lupus nephritis through fetal Wnt-steroid hormone and epigenetic reprogramming in MRL/lpr mouse offspring.

We previously investigated whether maternal high-fat diet (HFD) exposure alters lupus nephritis (LN) progression in MRL/lpr offspring. Contrary to expectation, maternally HFD-exposed offspring showed delayed and attenuated nephritic progression compared with control diet offspring. The maternal HFD developmental impact on LN remains unclear. Here, integrated amniotic fluid metabolomics and fetal liver transcriptomics revealed that maternal HFD reshaped the intrauterine molecular environment, particularly involving steroid hormone biosynthesis and Wnt/β-catenin-associated regulatory networks. Methylome profiling further demonstrated broad CpG hypomethylation, immune-related differentially methylated region enrichment, and an inverse association between global CpG methylation and oxidative genomic DNA damage. Among candidate regulatory nodes, Axin2, a canonical Wnt/β-catenin target and feedback regulator, emerged as a potential link between fetal nutritional exposure, epigenetic remodeling, and persistent pathway modulation. Although whole-locus and gene body methylation of Axin2 were not markedly altered, promoter-region methylation showed an increasing tendency under maternal HFD exposure. In adult offspring, maternal HFD was associated with reduced Axin2 protein expression, decreased Wnt-responsive transcripts, increased peripheral corticosterone levels, and attenuation of LN progression. The inverse association between Axin2 expression and corticosterone further suggested coupling between suppressed Wnt pathway output and steroid hormone remodeling. Together, these findings support a developmental model in which maternal HFD reshapes the fetal intrauterine environment and establishes a persistent Wnt-steroid hormone-epigenetic regulatory axis that unexpectedly attenuates LN progression in genetically susceptible offspring.

Axin2↗

PubMed2025

Single-cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism.

Duplication 15q (dup15q) syndrome is a leading genetic cause of autism spectrum disorder, offering a key model for studying autism-related mechanisms. Using single-cell and single-nucleus RNA sequencing of cortical organoids from dup15q patient-derived iPSCs and post-mortem brain samples, we identify increased glycolysis, disrupted layer-specific marker expression, and aberrant morphology in deep-layer neurons during fetal-stage organoid development. In adolescent-adult postmortem brains, upper-layer neurons exhibit heightened transcriptional burden related to synaptic signaling, a pattern shared with idiopathic autism. Using spatial transcriptomics, we confirm these cell-type-specific disruptions in brain tissue. By gene co-expression network analysis, we reveal disease-associated modules that are well preserved between postmortem and organoid samples, suggesting metabolic dysregulation that may lead to altered neuron projection, synaptic dysfunction, and neuron hyperexcitability in dup15q syndrome.

Humans↗

PubMed2026

Integrative multi-omics profiling of insomnia-related molecular features reveals microbiome, immune, and therapy-relevant heterogeneity in colorectal cancer.

Emerging evidence implicates insomnia as a potential risk factor in carcinogenesis, potentially involving systemic inflammation, circadian disruption, and microbiome alterations. However, the molecular associations linking insomnia-related features to colorectal cancer (CRC), particularly with respect to tumor biology, immune microenvironmental states, and therapy-relevant phenotypes, remain largely unexplored. Multi-omics integration of genomic, transcriptomic, and microbiome data from 3,026 CRC patients across seven independent cohorts, including a large, well-annotated Clinical Omics study of Colorectal Cancer in China (COCC) cohort, enabled insomnia-based molecular classification through unsupervised non-negative matrix factorization (NMF) clustering. The insomnia subtype (IS) was biologically characterized via pathway enrichment, immune deconvolution, microbial profiling, and single-cell transcriptomics. Furthermore, an insomnia score (ISscore) was developed and validated in multiple cohorts for risk stratification and assessment of treatment-response-related indicators in CRC. Unsupervised clustering revealed two distinct molecular subtypes (IS1/IS2), with IS2 demonstrating significantly poorer survival. IS2 exhibited marked activation of EMT/angiogenesis pathways versus cell cycle activation in IS1. The IS2 microenvironment showed increased immunosuppression-related infiltration and exhausted T cell signatures, together with intratumoral microbiome variation characterized by depletion of Ruminococcaceae UCG-002 and enrichment of Hungatella/Selenomonas. The ISscore system stratified survival risk and was associated with computational indicators of immunotherapy response. Single-cell analysis nominated PPIA-BSG as a potential cell-cell communication signal involving high-ISscore tumor cells, CXCL12+ endothelial cells, and CLEC9A+ dendritic cell subsets. This multi-omics characterization of insomnia-CRC interplay suggests that insomnia-related molecular features are associated with an immunologically distinct and microbiome-altered tumor ecosystem. The ISscore provides a reproducible framework for capturing insomnia-related molecular heterogeneity, supporting risk stratification and future evaluation of therapy-relevant phenotypes.IMPORTANCEChronic insomnia affects millions, but it is not typically considered a cancer risk factor. Our study, analyzing vast biological data from over 3,000 colorectal cancer patients, uncovers a potential link between a person's predisposition to insomnia and their risk of developing this disease. This suggests that the biological pathways related to sleep may play a role in cancer development. Understanding this connection opens up new avenues for identifying individuals at higher risk and developing novel prevention strategies for colorectal cancer.

colorectal cancer↗