Biomedical subjects

Zhe Wang

Publications and source records attributed to Zhe Wang.

13 recordsLinked to original sources

PubMed2026

Machine learning and multi-omics clustering to map cellular rewiring and immune evasion in ccRCC.

Immune checkpoint blockade (ICB) efficacy in clear cell renal cell carcinoma (ccRCC) is limited by tumor microenvironment (TME) heterogeneity. Because traditional bulk-derived models lack spatial resolution, we developed an integrated framework connecting macroscopic survival risks to microscopic TME structures. We applied ten algorithms to establish multi-omics subtypes and evaluated 101 machine-learning combinations across three independent cohorts to generate a Consensus Machine Learning-driven Signature (CMLS). The signature's spatial and cellular origins were decoded using spatial transcriptomics (ST) and a 140,000-cell scRNA-seq atlas. Expression of key genes was experimentally validated via RT-qPCR in 17 paired ccRCC clinical tissues. We identified two molecular subtypes with distinct clinical and epigenetic profiles. SuperPC optimization yielded a 24-gene CMLS serving as an independent prognostic factor. scRNA-seq and ST deconvolution revealed these signals predominantly originate from cancer-associated fibroblasts (CAFs) and malignant epithelial cells, which collaborate to drive spatial immune exclusion. RT-qPCR confirmed significant overexpression of five core CMLS genes in ccRCC versus adjacent normal tissues. Low CMLS scores correlated with enhanced ICB responsiveness, whereas high-CMLS tumors demonstrated specific vulnerability to dasatinib and dabrafenib. The CMLS translates spatial immune-exclusion dynamics into a quantifiable metric, outperforming tumor mutational burden in predicting ICB benefits, providing a robust tool for patient stratification in ccRCC.

Humans↗

PubMed2026

The complete genomic sequence of a novel member of the genus Caulimovirus isolated from Dregea volubilis.

A novel caulimovirus was identified from diseased leaves of Dregea volubilis exhibiting yellowing and vein-associated chlorosis in Yuanjiang County, Yunnan Province, China. The virus was tentatively named Dregea volubilis caulimovirus 1 (DVCaV1). The complete genome sequence of DVCaV1, determined by de novo assembly of high-throughput sequencing data, comprises 8,160 bp of circular double-stranded DNA containing two intergenic regions and seven open reading frames (ORFs). These ORFs encode (in order) a movement protein (MP), an aphid transmission factor (ATF), a virion-associated protein (VAP), a coat protein (CP), a polymerase polyprotein (Pol, containing protease, reverse transcriptase, and RNase H domains), a transactivator/viroplasmin (TAV) protein, and a hypothetical protein of unknown function. Sequence comparisons revealed the highest nucleotide similarity with strawberry vein banding virus (SVBV; NC_001725). Phylogenetic analysis confirmed DVCaV1 as a member of the genus Caulimovirus, with SVBV as its closest known relative. According to current ICTV species demarcation criteria for the genus Caulimovirus (host range and > 20% nucleotide sequence divergence in the polymerase region), DVCaV1 represents a novel species. This is, to our knowledge, the first report of a caulimovirus detected in naturally symptomatic Dregea volubilis.

Genome, Viral↗

PubMed2026

The metastatic spectrum in functional and non-functional NENs: mechanistic insights from multi-omics.

Neuroendocrine neoplasms (NENs) are biologically heterogeneous tumors in which differentiation/grade and hormonal functionality are intersecting but non-equivalent axes. This review focuses on functional and non-functional well-differentiated neuroendocrine tumors (NETs), principally gastroenteropancreatic and pancreatic NETs, and critically evaluates how site, lineage, stage, tumor burden, genomic and epigenetic alterations, immune-stromal remodeling, metabolic adaptation, microbiome-associated signals, and treatment pressure converge on metastasis and recurrence. Apparent outcome differences by functionality are inconsistent after clinicopathological adjustment: non-functional presentation is often enriched for delayed diagnosis and adverse features, whereas functional subtypes range from typically indolent insulinomas to clinically aggressive hormone-producing tumors. We reconcile these observations through a layered model in which lineage-defining alterations and chromatin/telomere programs establish cellular state; signaling and metabolic plasticity enable stress adaptation; and hypoxia, angiogenesis, immune cells, fibroblasts, extracellular matrix, and therapy create selective niches for dissemination and relapse. We also define computational strategies for heterogeneous multi-omics integration and a staged biomarker-validation pathway. Evidence remains dominated by pancreatic NETs, and causal support is weakest for microbiome-functionality relationships and several proposed cross-omic links. A spectrum-based framework is therefore most useful when it generates testable, site- and grade-specific hypotheses rather than treating functionality as an isolated prognostic variable.

Humans↗

PubMed2026

Metagenomic insights into biogeochemical functional potential and resistome dynamics of PM2.5 microbial communities.

Atmospheric particulate matter harbors diverse microorganisms, yet their functional potential in biogeochemical cycling and the associated risks of resistome remain poorly understood. Here, we performed metagenomic sequencing on PM2.5 samples collected across four months to unravel the microbial genetic repertoire involved in methane, nitrogen, phosphorus, and sulfur cycling, as well as the resistome, and pathogen composition. A broad range of functional genes was detected for each biogeochemical cycle, with more than 65% of gene subtypes shared across all months, indicating conserved functional signatures. In contrast, more than 80% of the resistome showed temporal variation in abundance, with the lowest richness observed in March. Temporal shifts were also observed in resistome composition, with several resistance determinants reaching higher abundances in April and May. Network analysis indicated frequent co-occurrence among several pathogenic and opportunistic taxa. Contig-based profiling identified 51 potential pathogenic taxa, including 32 human- or animal-associated taxa. In addition, both PM10 and PM2.5 concentrations were associated with pathogen abundance and functional gene richness (e.g., antibiotic resistance genes and virulence factors). Together, this metagenomic survey suggests contrasting temporal patterns between conserved biogeochemical functional potential and more variable resistome-related traits in PM2.5 microbial communities. While constrained by limited temporal coverage and sample size, this study provides preliminary insights into the ecological and potential public health relevance of airborne microbial communities in urban environments.

Particulate Matter↗

PubMed2026

Genome-wide identification and expression analysis of the UGT gene family in honeysuckle.

BACKGROUND: The UGT gene family plays critical roles in regulating plant growth, development, stress responses, and secondary metabolite synthesis. Although UGT proteins have been studied in numerous plant species, research on the UGT family in honeysuckle (Lonicera japonica Thunb.) remains limited. RESULTS: In this study, a comprehensive genome-wide analysis of the UGT gene family was performed in honeysuckle. A total of 224 unique LjUGT genes were identified and classified into 21 distinct subfamilies (T71-T92 without T77) based on the phylogenetic analysis. These genes were unevenly distributed on the 9 chromosomes. Eighteen segmental duplication events and 61 tandem duplications were identified, of which only 3 were positive selection. Integrated analysis of promoter cis-acting elements, transcription factors, targeted miRNAs, and interacting proteins suggested that the expression and function of the LjUGT genes may be regulated by transcription factors and proteins through binding to the various binding sites and cis-acting elements, thereby putatively participating in diverse biological processes, including hormone signaling, stress response, and metabolism. The expression pattern analysis of LjUGTs in different tissues and under stress conditions indicated that Lj2A1135G32, Lj5A236T61, Lj6A350T83, and Lj7A737T47 emerged as candidate genes potentially associated with development, 46 genes showed expression changes under all 6 abiotic stresses, suggesting broad stress responsiveness. Additionally, there 7 genes were identified as candidate hub genes that may correlate with the low temperature stress tolerance in honeysuckle according to the WGCNA results, and further verification by qRT-PCR confirmed that Lj4A99G61 and Lj9A591T82 can be regarded as key candidate genes for in-depth research. CONCLUSIONS: This study systematically identified 224 LjUGT genes in honeysuckle for the first time and characterized their physicochemical properties, phylogenetic relationship, and expression patterns. These findings provide a foundational resource for hypothesis-driven investigations into the functions and action mechanisms of LjUGTs.

Lonicera↗

PubMed2026

Assessing the Safety and Probiotic Potential of Bifidobacterium longum subsp. infantis BI45: A Comprehensive Study from Genomic Analysis to Randomized Controlled Clinical Trial in Healthy Adults.

While probiotics are increasingly consumed for health benefits, comprehensive safety assessments, particularly for novel strains, are imperative. This study aimed to conduct a holistic safety and efficacy assessment of Bifidobacterium longum subsp. infantis (B. infantis) BI45, spanning genomic analysis, in vitro tests, In vivo toxicity test, and a clinical trial. The safety of B. infantis BI45 was evaluated through: (1) whole-genome sequencing for antibiotic resistance and virulence genes; (2) in vitro phenotyping (hemolysis, cytotoxicity, gastrointestinal tolerance and antibiotic susceptibility); (3) an acute oral toxicity study in mice; and (4) a randomized, double-blind, placebo-controlled clinical trial. Forty-eight healthy adults were recruited and randomly assigned to receive either B. infantis BI45 or a placebo (n = 24/group) for 8 weeks. Hematological, biochemical, immunological, and gut microbiota parameters were assessed. Genomic analysis identified no transferable antibiotic resistance or virulence genes. In vitro assays confirmed the absence of hemolytic and cytotoxic activity, alongside high gastrointestinal tolerance. Antibiotic susceptibility testing showed that B. infantis BI45 is sensitive to a range of antibiotics. No adverse effects were observed in the murine toxicity study at 2 × 10¹⁰ CFU/kg. Importantly, the clinical intervention revealed no adverse events or significant alterations in hematological, hepatic, or renal function markers in the B. infantis BI45 group, demonstrating an excellent safety profile. Furthermore, B. infantis BI45 supplementation significantly increased serum levels of immunomodulatory markers Immunoglobulin A (IgA) and antimicrobial peptide LL-37 compared to the placebo (p < 0.05) and modulated the gut microbiota by enriching beneficial short-chain fatty acid producers. The multi-tiered evidence demonstrates that B. infantis BI45 is a safe probiotic strain that does not induce adverse reactions in healthy adults. Its consumption positively modulates host immunity and the gut microbiota.Trial Registration Number: NCT06863415 (ClinicalTrials.gov).

Adult↗

PubMed2026

Microbiota-gut-muscle axis shapes fish muscle texture by regulating collagen synthesis.

BACKGROUND: Increasing studies have emphasized the communication network between the gut microbiome and host organs, revealing that such interactions significantly influence host physiological performances. However, whether a gut-muscle axis exists to regulate muscle quality in animal production is unknown. RESULTS: In two independent cohorts, the muscle hardness of tilapia subjected to a long-term faba bean diet exhibited significant inter-individual variation. RNA-Seq analyses of the high-hardness (H) and low-hardness (L) groups pointed to collagen-based extracellular matrix as a possible factor driving muscle hardness development. Transplantation of gut microbiota from the H donor resulted in enhanced collagen synthesis in gnotobiotic zebrafish. Muscular collagen deposition was featured with an increased abundance of gut Cetobacterium. Gnotobiotic models colonized with live C. somerae exhibited enhanced collagen synthesis. Integrated analyses of microbiome function, bacterial genome, and metabolic profiles identified acetate as a key effector of C. somerae. Acetate incubation upregulated collagen I expression in TGF-β-activated fibroblasts in an acetylation-dependent manner. Mechanistically, acetate promoted the acetylation of SMAD2/3, enhancing its nuclear transport and stability, which ultimately increased collagen expression. An acetate-supplemented feeding experiment corroborated these findings. CONCLUSION: The comprehensive results provided evidences that gut microbes regulated tilapia muscle texture through SMAD2/3 acetylation-driven collagen synthesis. This study expands our understanding of the multifaceted role of the gut-muscle axis in muscle physiology. Furthermore, our findings highlight that targeting gut microbiota and the downstream collagen synthesis pathway could be promising for manipulating muscle quality in animal production. Video Abstract.

Animals↗

PubMed2026

Genome-Guided Discovery of Antimalarial 4-Amino-2,4-Pentadienoate-Containing Cyclolipodepsipeptides.

4-Amino-2,4-pentadienoate-containing cyclolipodepsipeptides (APD-CLDs) represent a structurally distinctive family of natural products known for their selective activity against hypoxic cancer cells. To explore the structural diversity of APD-CLDs, we have identified and prioritized cryptic APD-CLD biosynthetic gene clusters (BGCs) for compound discovery. Using a combination of genetic and chemical methods, we successfully activated three dormant BGCs, leading to the discovery of 12 new APD-CLDs. These newly discovered metabolites significantly expanded the diversity of the APD-CLD family, with chloromalamides and arabimalamides representing the first halogenated and glycosylated members, respectively. Unexpectedly, chloromalamides and arabimalamides exhibited potent antiplasmodial activity, with IC50 values in the 25-161 nM range against drug-sensitive and multidrug-resistant Plasmodium falciparum strains. Phenotypic studies revealed arabimalamide B halted parasite development during the asexual blood stage life cycle, resulting in enlarged digestive vacuoles, dispersed hemozoin, and ultimately reduced reinvasion efficiency. These phenotypes are reminiscent of the effect of chloroquine and other 4-aminoquinoline drugs, suggesting that arabimalamides may disrupt the parasite's heme detoxification mechanism. Biosynthetic studies identified key scaffold-forming and modifying enzymes, including a rare membrane glycosyltransferase in arabimalamide biosynthesis. Together, these findings unveil APD-CLDs as new antimalarial lead scaffolds and set the stage for structural diversification and optimization.

Antimalarials↗

PubMed2025

Cetobacterium somerae ZNN-1 promotes goblet cell differentiation through glutamine-mediated Notch signaling suppression.

INTRODUCTION: The gut microbiota acts as a crucial mediator in the interaction between the diet components and the host metabolism. However, the molecular mechanism by which the gut microbiota adapts to dietary components and subsequently regulates host physiological responses remains unclear. OBJECTIVES: This study aimed to investigate the response of gut microbiota to a plant-based protein diet (soybean meal, SM) and the effects of gut microbiota on host intestinal barrier function, along with the underlying mechanisms in a fish model. METHODS: Histopathological examination, and transepithelial electrical resistance test were used to evaluate the effects of Cetobacterium somerae on intestinal barrier function. Potential molecular mechanisms were validated by integrating whole-genome sequencing, microbiota composition sequencing, transcriptomics, and metabolomics, and utilizing in vitro cell models and mouse-derived organoid models. RESULTS: The results revealed that the SM diet significantly increased the abundance of Cetobacterium somerae in fish. Administration of C.somerae ZNN-1, a dominant strain isolated from the intestine of fish fed with the SM diet, enhanced the intestinal barrier function, particularly increasing the number of goblet cells in the intestine. Whole genome analysis of C. somerae ZNN-1 showed carbohydrate metabolism-associated genes were the most abundant in its metabolic modules. C.somerae ZNN-1 supplementation significantly inhibited the Notch signaling pathway in fish intestine. Metabolomics analysis revealed that administration of C.somerae ZNN-1 increased the glutamine level in fish gut. In vitro experiments demonstrated that glutamine regulated the differentiation of goblet cell by inhibiting the Notch signaling pathway in both human intestinal epithelial cell model and mouse intestinal organoid model. CONCLUSION: C. somerae served as a key bacterium adapted to soybean meal-derived carbohydrates, and it promoted goblet cell differentiation by inhibiting the Notch pathway. This study provides a new perspective for unraveling the interaction mechanisms among diet components, intestinal microbiota and host health.

Animals↗

PubMed2025

An integrated multiscale air quality modelling framework for industrial park pollution: Linking local emissions to regional transport.

Capturing the spatiotemporal distribution of pollutants in industrial parks remains challenging for regional air quality models because of their coarse resolution (3 km), resulting in uncertainties in local emission quantification. To address this, we developed the Integrated Multiscale Air Quality Modelling System for Industry (IAQMS-Industry), coupling the regional Nested Air Quality Prediction Modelling System (NAQPMS) with a city-scale chemical transport model. This framework integrates point-source locations and Gaussian plume dispersion to simulate particulate matter with a diameter smaller than 2.5 micrometres (PM2.5) at 100 m resolution. Applied to the Beijing Yi Zhuang and Tangshan industrial parks and evaluated against observations. The coupled model achieved a normalized mean bias (NMB) ranging from 3.1 % to 6.2 %, improving upon NAQPMS (-16.9 % to -7.7 %). Spatial analysis revealed that coarse regional grids underestimated the PM2.5 concentrations at industrial sites by smoothing gradients, whereas IAQMS-Industry successfully resolved spatial patterns. Industrial point emissions accounted for 22.9 %-26.4 % of PM2.5 in the coupled model, which was significantly greater than the regional model estimates of 1.6 %-13.7 %. These findings indicate that regional models overestimate pollutant dispersion processes in industrial parks while underestimating local industrial impacts. By explicitly resolving point-source dynamics and linking them to regional transport, IAQMS-Industry provides a robust tool for designing targeted emission controls in industrial cities and balancing local air quality improvements with minimized regional pollution outflow. This study underscores the necessity of multiscale modelling for accurate source apportionment and informed environmental governance in industrial zones.

Air Pollution↗

PubMed2025

Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.

BACKGROUND: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability. RESULTS: Here, we conduct the largest meta-analysis of whole genome sequencing for low-density lipoprotein cholesterol (LDL-C), a therapeutic target for coronary artery disease, analyzing data from 246 K participants and integrating 1.23B variants from the UK Biobank and the Trans-Omics for Precision Medicine (TOPMed) program. We identify numerous rare coding and non-coding gene associations related to LDL-C, with replication across 86 K participants in All of Us. Our findings are based on single-variant analyses, rare coding and non-coding variant aggregation tests, and sliding window approaches. Through this comprehensive analysis, we identify 704 novel single-variant associations, 25 novel rare coding variant aggregates, 28 novel rare non-coding variant aggregates, and one novel sliding window aggregate. CONCLUSIONS: This study provides a meta-analysis framework for large-scale whole genome sequence association analyses from diverse population groups, yielding novel rare non-coding variant associations.

Humans↗

PubMed2025

Structure-activity relationships study on inhibition of CRISPR-Cas9 by glycosaminoglycans.

The CRISPR-Cas9 system is a revolutionary genome editing system known for its precision, simplicity and efficiency, playing a crucial role in gene-editing. It has enabled applications ranging from biomedicine to agriculture. However, the uncontrollable activity of Cas9 has raised significant safety concerns in clinical settings, limiting its broader application. Consequently, regulating CRISPR-Cas9 activity holds substantial promise for enhancing the safety and efficacy of gene-editing technologies. In this study, we demonstrated that sulfated glycosaminoglycans (GAGs) exhibit inhibitory effects of Cas9. Specifically, both chondroitin sulfate (CS) and heparin (HP) can inhibit CRISPR/Cas9 activity, with heparin showing a stronger inhibitory effect that correlates positively with its concentration. Molecular dynamics simulations indicate that sulfated heparin residues might inhibit Cas9 function by binding to essential DNA-binding sites, which are crucial for functional interactions, potentially impairing activity. Additionally, higher molecular weight GAGs exhibit enhanced inhibitory effects under the same sulphation. Notably, the sulfation site also influenced activity. C6-sulfation of chondroitin sulfate is more favorable for Cas9 inhibition, and N-sulfation of heparin enhances its inhibitory effect on Cas9 activity. These findings provide valuable insights into the development of carbohydrate-based inhibitors for CRISPR-Cas9, offering a foundation for further exploration in this field.

CRISPR-Cas Systems↗

PubMed2024

Comprehensive Proteomic Analysis Reveals Distinct Features and a Diagnostic Biomarker Panel for Early Pregnancy Loss in Histological Subtypes.

Early pregnancy loss (EPL) is a common event in human reproduction and is classified into histological subtypes such as hydropic abortion (HA) and hydatidiform moles, including complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs). However, accurate diagnosis and improved patient management remain challenging due to high rates of misdiagnosis and diverse prognostic risks. Therefore, diagnostic biomarkers for EPL are urgently needed. Our study aimed to identify biomarkers for EPL through comprehensive proteomic analysis. Ten CHMs, six PHMs, ten HAs, and 10 normal control products of conception were used to obtain a proteomic portrait. Parallel reaction monitoring-targeted proteomic and regression analyses were used to verify and select the diagnostic signatures. Finally, 14 proteins were selected and a panel of diagnostic classifiers (DLK1, SPTB/COL21A1, and SAR1A) was built to represent the CHM, PHM, and normal control groups (area under the receiver operating characteristic curve = 0.900, 0.804/0.885, and 0.991, respectively). This high diagnostic power was further validated in another independent cohort (n = 148) by immunohistochemistry (n = 120) and Western blot analyses (n = 28). The protein SPTB was selected for further biological behavior experiments in vitro. Our data suggest that SPTB maintains trophoblast cell proliferation, angiogenesis, cell motility, and the cytoskeleton network. This study provides a comprehensive proteomic portrait and identifies potential diagnostic biomarkers. These findings enhance our understanding of EPL pathogenesis and offer novel targets for diagnosis and therapeutic interventions.

Humans↗