Biomedical subjects

Meng Wang

Publications and source records attributed to Meng Wang.

11 recordsLinked to original sources

PubMed2026

Genome-wide identification of CHY zinc finger and RING finger (CHYR) genes in pepper and functional characterization of CaCHYR5 in response to Phytophthora capsici infection.

CHY zinc finger and RING finger (CHYR) proteins play crucial roles in the growth and development, as well as stress response. To date, no systematic or comprehensive analysis of the CHYR gene family has been performed in pepper (Capsicum annuum L.). In this study, we identified 8 CaCHYR genes (CaCHYR1-CaCHYR8), which were classified into 3 groups based on phylogenetic relationships. CaCHYR members within the same group exhibited similar distributions of conserved motifs and exon-intron structures. Chromosomal localization analysis showed that 8 CaCHYR genes were unevenly distributed on 6 chromosomes. Segmental duplication, rather than tandem duplication, was found to be the major contributor to the expansion of this gene family. CaCHYR genes feature a variety of cis-elements involved in developmental processes, phytohormone responses, and stress adaptation. Expression analysis based on RNA-seq data revealed that CaCHYR genes exhibited distinct spatial expression patterns across different tissues and in response to Phytophthora capsici infection (PCI), and quantitative real-time PCR (qRT-PCR) further confirmed that three of them (CaCHYR2, CaCHYR3, and CaCHYR5) exhibited altered expression under PCI. Furthermore, transient overexpression of CaCHYR5 in pepper leaves increased susceptibility to PCI, suggesting its potential negative regulatory role in pepper defense against P. capsici. Collectively, these findings reveal the expression patterns and regulatory functions of pepper CHYR genes in growth and development, laying a groundwork for breeding pepper cultivars tolerant to PCI.

Phytophthora capsici infection (PCI)↗

PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗

PubMed2026

Genome-Wide Characterization of the ZIP Transporter Family in Sea Island Cotton (Gossypium barbadense L.) and Expression Profiling Under Heavy Metal and Pathogen Stresses.

G. barbadense represents an indispensable germplasm resource for high-quality textile fiber and disease resistance; nevertheless, systematic information regarding its ZRT/IRT-like protein (ZIP) gene family remains limited. Here, a total of 46 GbZIP genes were identified across the G. barbadense genome. Comprehensive bioinformatic investigations revealed uneven chromosomal distribution and confirmed that segmental/whole-genome duplications, supplemented by localized tandem duplications, drove family expansion. Members clustered within the same phylogenetic clades shared conserved motif organization and gene architecture, while promoter regions harbored abundant cis-acting elements associated with phytohormone and stress signaling. Transcriptome profiling indicated distinct expression patterns across vegetative/reproductive tissues, fiber and ovule developmental stages, and diverse abiotic stress conditions (cold, hot, drought, and salt). Quantitative Real-Time PCR (qRT-PCR) further validated that several GbZIP candidates exhibited temporal expression variations upon exposure to cadmium toxicity, V. dahliae infection, and combined Cd-V. dahliae stress. Specifically, GbZIP13, GbZIP18, GbZIP27, and GbZIP36 displayed prominent broad-spectrum responses to all three stress conditions, whereas GbZIP16, GbZIP29, and GbZIP30 showed stress-specific regulatory divergence. Overall, this study aims to systematically analyze the evolutionary characteristics and expression patterns of the GbZIP family, and to specifically evaluate the response differences under Cd stress, V. dahliae stress, and combined stress, in order to identify potential key candidate genes.

Gossypium barbadense↗

PubMed2026

Hypertensive mt. tRNAIle4263A>G mutation orchestrates vascular senescence and apoptosis by activation of mitochondria-ER interplay.

The pathogenic mechanism underlying diseases caused by mitochondrial DNA (mtDNA) mutation, including hypertension, persists as an unresolved global challenge. Although mutation-induced mitochondrial defects have been well characterized, how these mito-perturbations are converted into critical intermediary signaling cascades and contribute to diseases remain unknown. Here, using human induced pluripotent stem cell (hiPSC)-derived vascular organoids (VOs) and vascular cells, the hypertensive mt. tRNAIle4263A > G mutation was identified to induce vascular senescence, apoptosis and vascular-specific dysfunction through mitochondria-endoplasmic reticulum (ER) interaction. For the first time, this study mapped the transcriptional reprogramming landscape of human VOs carrying this mutation. Through systematic screening and functional validation, ER stress was screened out, together with downstream mitochondria-associated ER membranes-mitochondrial Ca2+ overload resulting in vascular abnormality. Pathological reactive oxygen species (ROS) elevation, driven by tRNAIle destabilization and bioenergetic failure, acts as the primary instigator of maladaptive ER stress activation in this cascade. Pharmacological targeting of this axis-using mito-Tempol (a mitochondria-targeted ROS scavenger), Tauro Ursodeoxycholic Acid (an ER stress inhibitor), or RU265 (a highly-selective mitochondrial calcium uniporter inhibitor)-rescues vascular abnormality. This study highlights mt. tRNAIle4263A > G mutation orchestrates vascular pathology through ROS induced activation of inter-organelle communication, resolving a long-standing knowledge gap between mtDNA mutations and diseases and establishing therapeutic nexuses for mtDNA mutation-related cardiovascular diseases.

Hypertension↗

PubMed2026

Complete Genome Sequence of Atractylodes virus A, a Novel Carlavirus Infecting Atractylodes lancea.

Atractylodes lancea is an important medicinal crop, but viral diseases have become increasingly severe in recent years. Viruses in the genus Carlavirus are common plant pathogens that are primarily transmitted by aphids and can cause stunted growth and reduced yields in their host plants. In this study, a novel carlavirus, tentatively named Atractylodes virus A (AVA), was identified from A. lancea plants exhibiting virus-like symptoms. The full-length genome of AVA is 8,817 nt in length and contains six open reading frames, displaying the typical genomic organization of the genus Carlavirus. The replicase and CP exhibit 53.43% and 56.72% amino acid identity, respectively, with those of previously characterized carlaviruses, indicating that AVA represents a novel species in the genus Carlavirus. This study expands our understanding of viral diversity in A. lancea and provides a scientific foundation for the prevention and control of viral diseases as well as for resistance breeding.

Genome, Viral↗

PubMed2026

Excess folate elevates formaldehyde genotoxicity in cell lines but not in mice or humans.

Folate metabolites are chemically unstable: spontaneous decomposition releases formaldehyde, a genotoxin in blood stem cells and a human carcinogen. Despite this, folic acid consumption frequently exceeds the Recommended Dietary Allowance and is prescribed at high doses for patients with blood disorders. However, the impact of excess folate on endogenous formaldehyde genotoxicity in vivo has not been studied. We find that excess tetrahydrofolate (THF) treatment of cell lines elevates formaldehyde-DNA adducts and genotoxicity. To test this in vivo, we fed a high-folic acid diet (10-fold above standard) to mice with heightened sensitivity to formaldehyde: detoxification-impaired Adh5-/- mice, and Fanconi anemia DNA repair mutants Fanca-/- and Fancj-/-. In contrast to cell lines, elevated tissue THF was not associated with increased formaldehyde-DNA adducts nor blood stem cell attrition. Finally, in cancer patients, high-dose folic acid therapy elevated plasma folic acid but did not increase formaldehyde-DNA adducts in peripheral blood mononuclear cells. In conclusion, increased folate in vivo does not elevate endogenous formaldehyde genotoxicity in sensitized mouse models or humans.

Animals↗

PubMed2026

Spatially confined electrochemical strategy with DNA-assembled nanogaps for SNP detection.

Accurate detection of low-abundance single nucleotide polymorphisms (SNPs) against a large excess of homologous wild-type sequences requires both selective molecular recognition and effective transduction of small sequence differences into measurable signals. Here, we report a spatially confined electrochemical strategy that couples sequence-selective recognition with size-dependent mass-transport gating. DNA-hybridization-driven self-assembly of gold nanoparticles (AuNPs) forms a three-dimensional self-assembled electrode (3D-SAE) with a DNA-defined interparticle architecture. Competitive probes (SP/WP) convert single-base recognition into distinct molecular-size states: the SNP-associated pathway preferentially triggers a hybridization chain reaction (HCR), generating bulky AuNP-anchored HCR/methylene blue complexes (Au@HCR/MB) with reduced electrochemical accessibility through the porous 3D-SAE, whereas the wild-type pathway does not trigger HCR and maintains a high-current response from more readily accessible MB-containing species. Thus, sequence recognition is translated into a molecular-size difference and subsequently into an electrochemical signal through differential mass transport. Under buffer conditions, the platform achieved a statistically estimated detection limit of ∼0.47 fM and a quantitative range of 1 fM-100 pM. It discriminated a 0.1% mutant abundance in a fragmented genomic-DNA background. The downstream signal-transduction chemistry is enzyme-free and isothermal. This work establishes a mechanistical recognition-size-conversion-mass-transport-gating architecture for electrochemical nucleic acid analysis.

Polymorphism, Single Nucleotide↗

PubMed2026

Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.

End-stage renal disease (ESRD) remains a major clinical challenge with high morbidity and mortality, and its molecular mechanisms, particularly those shared among diverse primary kidney diseases during progression to ESRD, have not been studied. Here we conduct a large-scale two-stage epigenome-wide association study of ESRD in two independent cohorts consisting of 704 controls and 1031 ESRD cases. We identify 52 ESRD-associated differentially methylated CpG positions (ESRD DMPs) showing consistent association between the two cohorts and across diverse kidney diseases, implicating 144 candidate genes enriched in inflammatory and immune pathways. Five of the 52 DMPs are associated with ESRD complications, and seven with renal function decline in early-stage chronic kidney disease, demonstrating their potential as prognostic biomarkers for ESRD and its complications. Our findings highlight inflammation, immune dysregulation, and renal fibrosis as shared epigenetic drivers of ESRD progression, and identify biomarkers with potential utility for risk stratification and therapeutic intervention.

Humans↗

PubMed2026

ARISE: RNA-anchored shared-edge topology and hierarchical fusion for spatial multi-omics integration.

MOTIVATION: Spatial multi-omics technologies jointly profile transcriptomes, proteins and chromatin accessibility in situ, enabling integrative analysis of tissue organization across molecular layers. However, most existing graph-based integration methods rely on independently constructed modality-specific k-nearest-neighbor graphs. When auxiliary modalities are sparse or noisy, these graphs can become topologically discordant, propagate spurious edges, weaken cross-modal alignment, and reduce spatial domain resolution. RESULTS: We present Anchored RNA for Integrated Spatial Embedding (ARISE), an RNA expression anchored framework for spatial multi-omics integration. ARISE defines a shared-edge topology by intersecting RNA feature-similarity and spatial-proximity graphs, encodes auxiliary modalities on this common scaffold, and integrates them through inside-out hierarchical fusion. We further show theoretically that graph intersection minimizes false-positive edges within a broad class of k-of-r graph fusion rules, providing a principled basis for topology anchoring. Across various spatial multi-omics benchmarks spanning simulated and real datasets in bi-modal and tri-modal settings, ARISE improves spatial domain identification, cross-modal consistency, and preservation of tissue structure relative to existing methods. Furthermore, the learned representation supports biologically meaningful downstream analyses, including marker-based domain annotation, pathway enrichment, and cis-regulatory inference, indicating that ARISE yields a robust and interpretable framework for spatial multi-omics integration. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/XiangxiangWang-code/ARISE. The archived version used in this study is available at https://doi.org/10.6084/m9.figshare.32686137.v2.

Multiomics↗

PubMed2026

A divide and conquer strategy for recapitulating whole genome 3D structure using Hi-C data.

The three dimensional (3D) spatial organization of the genome is closely linked to biological functions and can be captured by Hi-C assays through interrogating genome-wide chromatin interactions. Methodologies for inferring 3D structures from Hi-C data summarized as a two-dimensional (2D) contact matrix can be broadly placed within the paradigms of optimization-based and sampling-based. Many optimization-based methods are capable of constructing whole genome 3D structures but do not account for spatial dependency in the 2D data matrix nor cell heterogeneity in bulk Hi-C data, which provide an average over millions of cells. Sampling-based methods, on the other hand, are probabilistic model-based and can account for not only dependency, heterogeneity, but also other features inherent in Hi-C data, such as over-dispersion and sparsity. However, whole-genome 3D structure recapitulation is too computationally expensive for sampling-based methods, while chromosome-by-chromosome strategies for sampling-based methods ignore important information on inter-chromosomal contacts. To address these issues, we propose the truncated Random effect EXpression-cut and paste (tREX-cap) method, which applies the tREX model within a divide and conquer strategy. The resulting method inherits the good data-feature-cognizant properties of tREX and, in the meantime, can efficiently infer the whole genome 3D structure. We demonstrate the performance of tREX-cap through an extensive simulation study and analyses of a Hi-C lymphoblastoid dataset and a Hi-C IMR90 dataset.

Humans↗

PubMed2026

Exploring Causal Links Between 91 Circulating Inflammatory Proteins and Hashimoto's Thyroiditis: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Increasing evidence has linked inflammation to Hashimoto's thyroiditis (HT) etiology. However, the causal role of circulating inflammatory proteins in HT remains uncertain. To investigate this, we conducted a bidirectional Mendelian randomization (MR) study. METHODS: Genetic data for 91 inflammatory proteins and HT were sourced from publicly available GWAS databases. The PhenoScanner database was then searched for pleiotropic SNPs associated with potential confounders. Inverse variance weighted (IVW) analysis was used as the primary analysis, simultaneously supplemented by five sensitivity analyses to strengthen the results. RESULTS: The results revealed that, after false discovery rate (FDR) correction, interleukin (IL)-12p40 was causally associated with increased risk of HT (OR [95% CI] = 1.295 [1.172, 1.431], p = 3.66 × 10-7, PFDR = 3.33×10-5). Conversely, none of the inflammatory proteins was a consequence of HT. CONCLUSION: This study suggests that IL-12p40 is probably one of the factors correlated with HT etiology, contributing to a better understanding of the pathogenesis of HT and underscoring the potential for therapeutic interventions targeting inflammatory proteins.

Humans↗