Biomedical subjects

Yao Wang

Publications and source records attributed to Yao Wang.

4 recordsLinked to original sources

PubMed2026

CoxFormer enables spatial omics inference with multimodal generative modeling.

Gene co-expression maps transcriptome-wide gene-gene relationships, yet high-quality estimates cover less than half the genome. Meanwhile, spatial omics either profiles restricted in situ panels or lacks cellular resolution. Extending co-expression transcriptome-wide could overcome these limitations by inferring unassayed gene expression at subcellular resolution. Here we show that CoxFormer integrates literature-derived gene knowledge with co-expression networks from bulk tissues and large-scale single-cell atlases to learn 512-dimensional representations for 32,016 human genes. These embeddings capture functional gene relationships and serve as a generative prior for spatial inference across platforms and modalities. Without requiring a matched single-cell RNA-sequencing reference, CoxFormer supports four applications beyond measured genes: histology-based expression imputation, gene activity prediction from chromatin accessibility, subcellular super-resolution inference, and pathological region detection. Together, CoxFormer extends gene embedding from gene- and cell-level tasks to whole-transcriptome spatial inference, providing a unified framework for biological analysis beyond the limited gene coverage of current spatial omics technologies.

Humans↗

PubMed2026

Causal effects of cholelithiasis on hepatopancreatobiliary diseases: a multi-cohort Mendelian randomization study.

BACKGROUND: Cholelithiasis is commonly associated with multiple hepatopancreatobiliary diseases, yet whether these relationships reflect causal mechanisms or shared risk factors remains unclear. METHODS: We performed a phenome-oriented two-sample Mendelian randomization (MR) analysis to evaluate the causal impact of genetic liability to cholelithiasis across hepatopancreatobiliary outcomes. Independent genome-wide significant variants were selected as instrumental variables. Primary analyses used inverse variance weighting, complemented by sensitivity analyses, reverse MR, and multivariable MR adjusting for body mass index (BMI). RESULTS: Genetic predisposition to cholelithiasis was associated with increased risk of acute pancreatitis and extrahepatic cholangiocarcinoma (eCCA), with consistent directionality across datasets.The association with acute pancreatitis was interpreted as a positive control, whereas the null association with alcohol-induced acute pancreatitis served as a negative control. No causal association was observed for portal vein thrombosis. Sensitivity analyses, including MR-PRESSO and MR Steiger filtering, supported the robustness and directionality of the causal estimates. Reverse MR analyses showed no consistent evidence supporting reverse causality. Multivariable MR indicated that observed effects were not fully explained by BMI-related pathways. CONCLUSION: These findings suggest that cholelithiasis susceptibility may contribute to the broader hepatopancreatobiliary disease network, extending its clinical relevance beyond a localized biliary disorder.

Mendelian Randomization Analysis↗

PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗

PubMed2025

Therapeutic Targeting of Decr1 Ameliorates Cardiomyopathy by Suppressing Mitochondrial Fatty Acid Oxidation in Diabetic Mice.

BACKGROUND: A significant increase in mitochondrial fatty acid oxidation (FAO) is now increasingly recognized as one of the metabolic alterations in diabetic cardiomyopathy (DCM). However, the molecular mechanisms underlying mitochondrial FAO impairment in DCM remain to be fully elucidated. METHODS: A type 2 diabetes (T2D) mouse model was established by a combination of high-fat diet (HFD) and streptozotocin (STZ) injection. Neonatal rat cardiomyocytes were treated with high glucose (HG) and palmitic acid (HP) to simulate diabetic cardiac injury. Gain- and loss-of-function approaches and RNA sequencing were utilized to investigate the role and mechanism of 2,4-dienoyl-CoA reductase 1 (Decr1) in DCM. RESULTS: By integrating the genomic data available in the Gene Expression Omnibus (GEO) with DCM rodents, we found that the transcriptional level of Decr1 was consistently upregulated in DCM (+255% for diabetic heart, p < 0.0001; +281% for diabetic cells, p < 0.0001). Cardiomyocytes-specific knockdown of Decr1 preserved cardiac function (+41% for EF, p < 0.0001; +24% for FS, p = 0.0052), inhibited cardiac hypertrophy (-34%, p < 0.0001), fibrosis (-69%, p < 0.0001), apoptosis (-56%, p < 0.0001) and oxidative damage (-59%, p < 0.0001) in DCM mice, while cardiomyocytes-specific overexpression of Decr1 aggravated DCM (-28% for EF, p = 0.0347; -17% for FS, p = 0.0014). Deletion of Decr1 prevented high glucose/palmitate (HG/HP)-induced hypertrophy (-22%, p = 0.0006), mitochondrial dysfunction and apoptosis (-74%, p < 0.0001) in cultured cardiomyocytes. Furthermore, RNA sequencing and functional analysis showed that Decr1 interacted with and upregulated pyruvate dehydrogenase kinase 4 (PDK4) in injured cardiomyocytes, and overexpression of PDK4 eliminated the benefits of Decr1 downregulation in DCM (-20% for EF, p = 0.0071; -28% for FS, p = 0.0022). Mechanistically, PDK4 acted as a kinase that induced phosphorylation and mitochondrial translocation of HDAC3. In the mitochondria, HDAC3 mediated the deacetylation of dehydrogenase trifunctional multienzyme complex α subunit (HADHA), contributing to excessive mitochondrial FAO and subsequent cardiac injury. From a screening of 256 natural products, we identified Atranorin and Kurarinone as potential inhibitors of Decr1, both demonstrating protective effects against DCM (Atranorin, +21% for EF, p = 0.0134; +24% for FS, p = 0.0006; Kurarinone, +20% for EF, p = 0.0183; +27% for FS, p = 0.0001). CONCLUSIONS: Our study delineates a molecular mechanism by which Decr1 potentiated higher mitochondrial lipid oxidation and cardiac damage by enhancing HADHA deacetylation through the PDK4/HDAC3 signalling pathway.

Animals↗