Biomedical subjects

Jun Zhou

Publications and source records attributed to Jun Zhou.

14 recordsLinked to original sources

PubMed2026

Genome-wide epigenomic atlas and multi-omics responses of Eriocheir sinensis to natural extreme heat.

BACKGROUND: Global climate warming has led to increasingly frequent and prolonged extreme summer heat events, posing severe environmental challenges to aquaculture systems. Extreme summer heat can disrupt the performance of pond-cultured ectotherms. The Chinese mitten crab (Eriocheir sinensis) is an economically important freshwater crustacean, but coordinated molecular differences following contrasting natural summers remain incompletely characterized. RESULTS: We performed a comprehensive multi-omics analysis integrating meteorological monitoring, mRNA/lncRNA transcriptomics, small-RNA profiling of miRNAs, DNA methylomics, and LC-MS metabolomics in E. sinensis populations collected from Yancheng, China, between 2020 and 2024. Across the ten farms, survival was significantly lower in 2024, whereas yield and the proportion of large individuals showed nonsignificant downward trends. Gene-set analyses showed negative enrichment of cellular heat-response, protein-folding, oxidative-phosphorylation, and mitochondrial ATP-production terms in the 2024 cohort at the time of sampling. The integrated transcript annotation contained 72,240 lncRNAs and 63,833 mRNAs, and CpG was the predominant methylation context. Differential methylation analysis identified 73 regions and 185 cytosines, with hypomethylated events predominating within the significant subset. Metabolomic profiles differed between annual cohorts and mapped to carbohydrate, lipid, and amino-acid pathways. Cross-omics integration prioritized eight candidate genes-ADCY9, UNC79, UBN1, IFT52, ACO2, LOC126986070, LOC127001126, and LOC126997895-and qPCR reproduced the reported directions of expression for selected RNAs. CONCLUSION: This study provides the first integrative multi-omics framework for understanding chronic heat adaptation in E. sinensis. By linking transcriptomic, epigenomic, and metabolic remodeling, we elucidate the molecular mechanisms underlying energy imbalance, epigenetic reprogramming, and immune dysregulation during prolonged thermal stress. These findings offer valuable insights and genomic resources for breeding heat-tolerant crab strains and improving aquaculture resilience under ongoing climate change.

DNA methylation↗

PubMed2026

Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.

De novo mutations (DNMs) are an important source of congenital diseases. With delayed parenthood and assisted reproductive technology (ART) use increasing, it is essential to elucidate how these reproductive factors influence DNMs and whether resulting mutations influence offspring health. Here we performed whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families, identifying 390,924 de novo single-nucleotide variants (dnSNVs). Paternal and maternal aging exhibited distinct mutational patterns, with maternal DNM accumulation accelerating at advanced ages. Increased paternal dnSNVs partially accounted for the association between advanced parental age and shorter gestational duration. Moreover, ART showed age-independent, procedure-specific effects: intracytoplasmic sperm injection (ICSI) and ovarian stimulation were associated with increased paternal and maternal dnSNVs, respectively, and ICSI-associated paternal dnSNVs also partially accounted for the association between ICSI and shorter gestational duration. In vitro embryo manipulation was associated with increased early post-zygotic mosaic mutations, particularly C > A substitutions linked to delayed neurocognitive development at 1 year. Collectively, these findings advance understanding of the determinants and consequences of de novo mutagenesis.

Journal Article↗

PubMed2026

Chinese expert consensus on precision testing and molecular diagnosis of pancreatic cancer (2025).

This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4-9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.

Humans↗

PubMed2026

A nucleolar stress gene signature enables quantitative scoring across multi-omics contexts.

The nucleolus is essential for ribosome biogenesis and cellular homeostasis, and its dysfunction can induce nucleolar stress, a process implicated in cancer and other diseases. However, nucleolar stress is commonly inferred from morphological changes or a limited set of functional assays, and quantitative approaches based on gene expression profiles remain lacking. Here, we integrate literature curation with multi-dataset screening to define a nucleolar stress gene signature and develop a nucleolar stress score (NuS) applicable to bulk transcriptomics, single-cell transcriptomics, proteomics, and spatial transcriptomics. Using this framework, we show in colorectal cancer models that oxaliplatin induces nucleolar stress, suppresses nascent rRNA synthesis, and activates p53 signaling, whereas these responses are attenuated in oxaliplatin-resistant cells. Combined with a ribosome biogenesis activity score (RiboSis), NuS captures related but distinct dimensions of nucleolar function and stratifies tumors into functional states associated with clinical outcomes. NuS-based analysis of perturbational transcriptomes further prioritizes compounds with putative nucleolar stress-inducing activity. Collectively, this study provides a quantitative framework for evaluating nucleolar stress and illustrates its applications in disease stratification and drug mechanism discovery.

Cell Nucleolus↗

PubMed2026

A TIGIT nanotrapping-guided STING-activatable immunometabolic strategy overcomes innate immune silence and T cell exhaustion in breast cancer.

Breast cancer exhibits a profoundly immunosuppressive tumor microenvironment (TME), where innate immune silence prevents antigen sensing and persistent T cell exhaustion limits effector responses, rendering most immunotherapies ineffective. Clinical profiling of 1093 The Cancer Genome Atlas (TCGA) cases identified a glucose-fueled glutathione (GSH)-glutathione peroxidase 4 (GPX4)-dihydrolipoamide S-acetyltransferase (DLAT) axis as a dominant metabolic shield that suppresses oxidative stress, and thereby enforces both stimulator of interferon genes (STING) silence and CD8+ T cell exclusion. To dismantle this barrier, we developed an immunometabolic nanotherapy, GOx/ES-CO-LDH@TIGIT-Nanotrap (TNT). In acidic tumors, proton-driven layered double hydroxide (LDH) disassembly releases glucose oxidase (GOx) and extremely small cuprous oxide (ES-CO). GOx depletes glucose and nicotinamide adenine dinucleotide phosphate (NADPH) to induce disulfidptosis, while ES-CO releases cuprous ions (Cu+) that trigger cuproptosis via binding to lipoylated mitochondrial proteins. Their mutual biochemical amplification produces a cycloacclerated disulfidptosis-cuproptosis cascade that collapses the GSH-GPX4-DLAT axis and restores STING activation. Meanwhile, the macrophage-derived T cell immunoreceptor with Ig and ITIM domains (TIGIT) Nanotrap sequesters CD155 to prevent T cell suppression. Together, this coordinated innate reactivation and adaptive rescue converts immune-cold tumors into STING-inflamed and T cell responsive lesions.

Female↗

PubMed2026

ELN orchestrates prometastatic and immunosuppressive niche in bladder cancer via TGFB1 autocrine signaling.

Bladder cancer (BCa) mortality is mainly driven by metastatic dissemination and an immunosuppressive tumor microenvironment. Here, we identify ELN (tropoelastin), an extracellular matrix protein abundantly secreted by cancer-associated fibroblasts (CAFs), as a critical determinant of these processes and a marker of poor prognosis. ELN promotes epithelial-mesenchymal transition (EMT), facilitates lymphatic spread, and induces immune dysfunction characterized by macrophage polarization toward an M2 phenotype and T cell exhaustion. Mechanistically, ELN functions as a binding partner of TGF-β receptor 2 (TGFBR2), thereby triggering SMAD2/3-dependent TGF-β1 secretion and establishing a feed forward signaling loop. This ELN/TGFBR2/TGF-β1 axis amplifies metastatic capacity and immunosuppressive signaling, ultimately accelerating disease progression and diminishing responsiveness to immune checkpoint blockade. Functional studies in BCa organoids and murine models demonstrated that pharmacologic blockade of the ELN-TGFBR2 interaction effectively suppressed tumor metastasis and restored antitumor immunity. Collectively, our findings establish ELN as a CAF-derived driver of metastasis and immune evasion in BCa. Targeting the ELN-TGFBR2 interaction offers a promising therapeutic strategy to limit metastatic progression and enhance the efficacy of immunotherapy in this lethal disease.

Animals↗

PubMed2026

Cohesin variants associated with human reproductive and developmental disorders.

The cohesin complex is an evolutionarily conserved multi-subunit protein assembly essential for sister chromatid cohesion, meiotic recombination, DNA double-strand break repair, and transcriptional regulation. Pathogenic variants in its subunits are implicated in a spectrum of reproductive and developmental disorders, including non-obstructive azoospermia, premature ovarian insufficiency, reproductive aging, aneuploidy, Cornelia de Lange syndrome, Roberts syndrome, cancer, and neuropsychiatric disease. Consequently, identifying cohesin mutations is a priority for precision diagnostics and personalized medicine. This review systematically summarizes the cohesin variants linked to these pathologies, exploring their molecular mechanisms and clinical manifestations. A deeper understanding of these variants is crucial not only for deciphering disease etiology but also for guiding the development of targeted diagnostic strategies and therapeutic interventions, ultimately improving patient management and outcomes.

Humans↗

PubMed2026

Downregulated lysyl oxidase in plasma extracellular vesicles: a biomarker linked to brain metastasis risk in lung adenocarcinoma.

BACKGROUND: Brain metastasis (BrM) is a leading cause of mortality in patients with lung adenocarcinoma (LUAD). Extracellular vesicles (EVs), which carry bioactive molecules, play a critical role in tumor microenvironment remodeling and exhibit metastatic organotropism, holding promise as liquid biopsy biomarkers. This study aims to identify plasma EV-derived proteins associated with LUAD-BrM. METHODS: A multi-omics framework was applied. Plasma EVs from 59 stage IV LUAD patients (30 BrM vs 29 non-BrM) were profiled using data-independent acquisition mass spectrometry proteomics. Candidate proteins were screened via bioinformatics and machine learning (LASSO/RF/SVM). Initial validation included tissue proteomics (n = 13), single-cell transcriptomics (TISCH2), and Western blot analysis of a subset of the discovery samples. Functional experiments were conducted in vitro. The lead candidate was ultimately validated in an independent plasma cohort (n = 158) through ELISA. RESULTS: Proteomic analysis implicated collagen-containing extracellular matrix (ECM) pathways. Lysyl oxidase (LOX), a key ECM cross-linking enzyme, was identified as a lead candidate. LOX and its family member LOXL1 were consistently downregulated in BrM tissues and plasma EVs. Single-cell analysis revealed decreased LOX expression specifically in BrM-associated fibroblasts, which showed suppressed ECM-related pathways. In vitro experiments supported a PI3K/AKT-LOX-ECM regulatory axis. Plasma EV-derived LOX demonstrated strong diagnostic performance in the independent cohort, with an AUC of 0.786 (95% CI 0.713iated fi. CONCLUSIONS: Our study establishes plasma EV-derived LOX as a promising non-invasive biomarker for LUAD-BrM through a comprehensive multi-omics validation strategy. We propose a model wherein downregulation of LOX, potentially driven by PI3K/AKT signaling in tumor-associated fibroblasts, contributes to ECM degradation and may promote brain-tropic metastasis. This finding offers new insights for risk stratification and timely intervention in LUAD patients.

Humans↗

PubMed2026

The Znf711-Phf8 complex functions as a transcriptional rheostat essential for neutrophil development.

Neutrophil differentiation is governed by a precise transcriptional and epigenetic program. Here, we identify the zinc finger protein 711 (Znf711) and its partner, the histone demethylase PHD finger protein 8 (Phf8), as essential regulators of terminal granulopoiesis. Contrary to their established role as a transcriptional activator-co-activator pair, we found that the Znf711- Phf8 complex operates through a repressive mechanism. Znf711 promotes neutrophil maturation in a DNA-binding-independent manner by sequestering Phf8. Upon loss of Znf711, Phf8 is recruited by the growth factor independent 1 transcription repressor (Gfi1aa) to the promoter of the master regulator c/ebpα, where SUMOylated Phf8 acts as a corepressor to inhibit its transcription. Furthermore, we delineate a positive feedback loop wherein C/ebpα directly activates znf711 expression, ensuring a high level of c/ebpα at the onset of differentiation. Our findings define the Znf711-Phf8 complex as a critical transcriptional rheostat in neutrophil development.

Humans↗

PubMed2026

An integrated culturomic and genomic database and analysis platform for methanogenic archaea.

Methanogenic archaea research is challenged by limited strain resources, fragmented genomic data, inconsistent genome quality, substantial uncultured lineages, and difficulties in laboratory culturing, hindering advances in biogas production, climate mitigation, and microbial ecology. These archaea play crucial roles in global carbon cycling and anaerobic environments, yet scattered data and unculturable strains limit systematic studies and applications. To address this, we created MethArDB (Methanogenic Archaeal Genome Database), a specialized database for methanogenic archaea, compiling 3919 genomes, 87 host-associated plasmids, and 42 phages, with standardized quality classifications (complete, scaffold, draft), protein sequences, and metadata on geography, habitats, metabolism, and inheritable elements. Integrated MethArCT (Methanogenic Archaeal Culturomics Toolkit) employs a dual-threshold orthologous/paralogous protein analysis to evaluate metabolic pathway completeness, predicting cultivation parameters and suggesting candidate cultivation strategies, including potential medium formulations and conditions, to support strain isolation. Overall, MethArDB and MethArCT form an integrated platform combining genomics and culturomics to facilitate methanogenic archaea research. Database URL:  http://methardb.cn.

Genome, Archaeal↗

PubMed2025

A cross-species multi-omics analyze uncovers conserved molecular mechanisms underlying age-related erectile dysfunction.

BACKGROUND: The urgent need for new treatments is driven by the challenging clinical situation of age-related erectile dysfunction (ARED). AIM: To clarify the conserved molecular mechanisms of ARED across species using multi-omics. METHODS: Rat and mouse models with ARED were developed to facilitate the extraction of mRNA and proteins from the corpus cavernosum for high-throughput sequencing. Bioinformatics techniques were employed to analyze differentially expressed genes and to conduct analyses using the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and protein-protein interaction networks. Verification of the results was carried out using immunofluorescence, hematoxylin-eosin staining, and Masson staining. OUTCOMES: The multi-omics profiles of ARED rats and mice were analyzed and validated across species. RESULTS: In both species, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses of transcriptomic and proteomic data revealed that differentially expressed genes were predominantly enriched in pathways associated with alterations in extracellular matrix composition, downregulation of mitochondrial activity, and disruption of protein homeostasis. Immunofluorescence analysis demonstrated an upregulation of reactive oxygen species expression, coupled with a downregulation of Aldh18a1, collagen, and collagen I expression in the corpus cavernosum of mice and rats with ARED. CLINICAL IMPLICATIONS: To offer a novel approach for enhancing the erectile function in patients with ARED. STRENGTHS AND LIMITATIONS: The primary strength of this study lies in its utilization of cross-species multi-omics sequencing, which has elucidated the conserved molecular mechanisms underlying ARED. However, a significant limitation is the absence of subsequent validation in patients with ARED. CONCLUSIONS: Cross-species multi-omics comparisons present a potentially innovative approach for elucidating the underlying mechanisms and identifying preventive and therapeutic targets for ARED.

aging↗

PubMed2025

Surgery/anesthesia may cause monocytes to promote tumor development.

BACKGROUND: The immune system of patients undergoing major surgery usually has obvious immune responses during the perioperative period, and the patient's immune status would affect the patient's prognosis. In this study single-cell sequencing technology was used to investigate the effect of surgery/anesthesia on peripheral blood mononuclear cells (PBMCs) in depth during the perioperative period. METHODS: We performed an in-depth analysis of our previously published data, which included a total of 4 patients were recruited in this study. Their peripheral blood samples were collected pre operation, 0, 24, and 48 h post operation, and then PBMCs were extracted, followed by single cell sequencing. The results of sequencing were analyzed with R packages seurat and scSTAR. Finally, RT-PCR technology was used to verify the expression of key genes in monocyte. RESULTS: The ratio of CD4+ and CD8+ T cells and Tregs showed little change, and the function of CD4+ and CD8+ T cells recovered soon. The function of Treg had not been restored 48 h post operation. Non-classical monocyte was impressed after surgery and showed no recovery trend within 48 h. Similar to scRNA-seq, the expression levels of MDM2 and SESN1 in patients with tumor increased significantly after surgery. CONCLUSIONS: Surgery/anesthesia had little effect on CD4+ and CD8+ T cells, and continued to affect the functional changes of Treg. It had more impact on monocytes, which may cause them to promote tumor development to a certain extent.

Humans↗

PubMed2023

Ypel5 regulates liver development and function in zebrafish.

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5-/- mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Animals↗

PubMed2020

LINC00922 regulates epithelial-mesenchymal transition, invasive and migratory capacities in breast cancer through promoting NKD2 methylation.

Breast cancer ranks as the major reason for mortality in women populations, accounting for 23% of all cancer deaths. One in every three Asian women encounters the risk of this cancer in their lifetime. Long intergenic non-coding RNAs (lincRNAs) have emerged as tumor promoters and suppressors. The molecular mechanism of breast cancer remains elusive. Therefore, the current study aimed to explore the role lincRNA LINC00922 plays in the development of breast cancer. Breast cancer tissues and adjacent tissues were obtained from 109 patients with breast cancer. The RNA extraction and quantification and immunohistochemical staining characterized the high expression of LINC00922 and low expression of NKD2 in breast cancer tissues in comparison to its adjacent counterparts. Furthermore, the ectopic expression and knockdown experiments were conducted to figure out the in vivo and in vitro effects of LINC00922 on breast cancer progression. The ectopically expressed LINC00922 activated the Wnt signaling pathway, promoted epithelial-mesenchymal transition, cell proliferative, invasive and migratory capacities, tumor growth and metastasis. Additionally, the RIP and ChIP assay identified that LINC00922 recruited DNMT1, DNMT3A and DNMT3B proteins in the promoter region of NKD2 to promote NKD2 promoter methylation, thus reducing the NKD2 expression. Moreover, the Wnt signaling pathway was activated subsequent to NKD2 silencing, which was reversed by LINC00922 silencing. Lastly, the anti-oncogenic effects of LINC00922 inhibition was antagonized after NKD2 knocked down. The current study provides evidence that LINC00922 acts as a tumor promoter by promoting NKD2 methylation. Hopefully, it provides a novel potential gene target for the treatment of breast cancer.

Adaptor Proteins, Signal Transducing↗