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Chao Wang

Publications and source records attributed to Chao Wang.

14 recordsLinked to original sources
PubMed2026

Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome.

BACKGROUND: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. METHODS: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. RESULTS: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10  - ⁴), adipose tissue (pCauchy = 1.5366 × 10 - ⁴), and liver (pCauchy = 1.0167 × 10 - ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 - ⁴), with no significant liver or epidermal enrichment. CONCLUSION: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.

Psoriasis↗
PubMed2026

Allelic variation and light-responsive regulation of FaMYB10-2 underlie tissue-specific anthocyanin accumulation in strawberry.

Anthocyanins critically determine fruit color, nutrition, and stress resilience in cultivated strawberry (Fragaria × ananassa), directly influencing consumer preference. Despite complex genetic and environmental regulation of their biosynthesis, the basis for tissue-specific pigmentation, notably the widespread occurrence of red skin and pale flesh, remains poorly understood. We integrated genomic, transcriptomic, and functional analyses across 200 cultivars to dissect receptacle pigmentation regulation. Approaches included FaMYB10-2 allele mining, promoter structural variant (SV) identification, expression profiling, regulatory interaction assays, and characterization of upstream light-responsive factors. FaMYB10-2 was identified as the key R2R3-MYB regulator of fruit anthocyanin biosynthesis. Alleles FaMYB10-2.2 and FaMYB10-2.3 encode truncated proteins retaining bHLH-binding capacity but lacking activation domains, functioning as dominant-negative repressors. A promoter SV 986 bp upstream of FaMYB10-2 was associated with reduced pale fruit due to cis-regulatory divergence. The SV (Alt) allele is prevalent in Asian cultivars, while the Ref allele is enriched in Western germplasm. Crucially, a light-responsive FaHYH-FaWRKY71 cascade activates FaMYB10-2 and structural genes haplotype-dependently, compensating for weak MYB activity in the skin. Our findings reveal a multilayered regulatory system integrating allelic variation, cis-regulatory divergence, and environmental signals, advancing anthocyanin understanding and providing engineering targets for polyploid crop color improvement.

Fragaria↗
PubMed2026

Genome-Wide Identification and Expression Pattern of the ANK Gene Family in Sorghum bicolor Under Salt Stress.

The Ankyrin-repeat proteins (ANKs) play a key role in plant development and in response to abiotic stress. This research identified family members of the ANK genes in Sorghum bicolor at the whole-genome level, analyzed their sequence characteristics, evolutionary relationships, and expression patterns, and provided a scientific basis for elucidating the functionality of SbANK genes and for salt-tolerant breeding. Using bioinformatics methods, this study conducted a comprehensive identification of the SbANK gene family, analyzing its physicochemical properties, domain composition, chromosomal distribution, colinearity relationships, promoter cis-acting elements, and conserved protein motifs. Transcriptomic data and qRT-PCR were used to detect changes in their expression under salt stress. A total of 186 ANK family members were identified in the Sorghum bicolor genome, classified into 13 subfamilies and unevenly distributed across 10 chromosomes. Intra-species colinearity analysis revealed 7 pairs of duplicated genes, while inter-species colinearity analysis showed that S. bicolor and Oryza sativa share 88 pairs of orthologs, far exceeding the number found in Arabidopsis thaliana (11 pairs). Promoter analysis indicated that SbANK genes are enriched with cis-acting elements associated with hormone responses (particularly MeJA elements, accounting for 51.7%) and stress responses (particularly anaerobic-inducible elements, accounting for 60.9%). Transcriptomic expression analysis revealed that SbANK genes exhibit distinct tissue specificity, with the ANK-IQ subfamily highly expressed in leaves and the ANK-M subfamily showing the most widespread response under salt stress. Expression levels of the 10 candidate genes showing the most significant responses to salt stress were analyzed using qRT-PCR. The results indicated that SbANK91, SbANK135, and SbANK136 were significantly upregulated under 200 mmol/L NaCl treatment. The SbANK family is distinguished by a large number of member genes and structural diversity, with the ANK-M subfamily being the primary group responding to salt stress. SbANK91, SbANK135, and SbANK136 are identified as putative candidate genes for salt stress responses.

Sorghum↗
PubMed2026

Development and validation of a serum peptidomic signature for early detection of asymptomatic ovarian cancer: A multi-center prospective study.

Early detection of asymptomatic ovarian cancer (asym-OC) remains a critical challenge, the failure of which underlies its high mortality. Performing serum peptidomic profiling of 843 participants in the cohort SOCFCP, we distill 1,081 initial features into a 7-marker panel for asym-OC detection via a biology-informed machine-learning (ML)-based feature selection strategy. Three markers significantly revert toward non-OC levels after surgery. Integrating the panel with age, CA125, and HE4, we develop and externally validate (n = 159) a LightGBM model, ProMS+. For early-stage OC detection, ProMS+ shows a specificity of 92.6% at 95.0% sensitivity, outperforming CA125 (44.7%), HE4 (11.2%), and Risk of Ovarian Malignancy Algorithm (ROMA) (24.0%), with an area under the curve (AUC) of 0.993. In a simulated high-risk population (n = 100,000; OC prevalence = 1%), ProMS+ yields a high AUC (0.983) and a higher positive predictive value than CA125, HE4, and Age + CA125 + HE4 combined model (0.201 vs. 0.027, 0.090, and 0.064). ProMS+ offers a promising, non-invasive, and interpretable approach for the early detection of asym-OC.

Humans↗
PubMed2026

Fate of antibiotic resistance genes during rural domestic wastewater treatment: Anaerobic unit as enrichment hotspot versus aerobic unit as attenuation zone.

Rural domestic wastewater treatment systems are important but understudied reservoirs for antibiotic resistance genes (ARGs), whose full-process migration mechanisms remain unclear. Herein, the contribution of each treatment unit of ARGs was investigated using metagenomic methods across two seasons in typical rural domestic wastewater treatment systems. Although a removal efficiency (69 % in winter and 22 % in summer) was observed for ARGs, higher antibiotic residues and temperature dramatically induced ARG occurrence in wastewater and horizontal gene transfer (HGT) risk during wastewater treatment. The ARG abundances in the anaerobic unit increased by 1.6-2.1 fold compared to the regulating pool, primarily driven by elevated mobile genetic element (MGE) activity. In sharp contrast, ARG reduction was achieved through ARG host removal and suppressed HGT potential in the aerobic unit. Notably, mobile ARGs were dominated by tetracycline resistance genes in winter and co-dominated by tetracycline and sulfonamide genes in summer, with most flanked by transposases. Key pathogenic hosts, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa carrying ARG-MGE complexes, were primarily concentrated in the regulating pool and the influent, forming high-risk upstream sources of dissemination. Partial least-squares path model highlighted MGEs as the primary drivers, and variance partitioning analysis indicated that MGEs account for 31 % of the explained variation in ARGs during wastewater treatment. In summary, the anaerobic unit was an ARG enrichment hotspot, while the aerobic unit as ARG attenuation zone during wastewater treatment. These findings provide crucial evidence to optimize rural wastewater treatment processes and to target the control of antibiotic resistance.

Wastewater↗
PubMed2026

Identification and formation pathways of oxidation products of chlorinated paraffins during ozonation in municipal wastewater.

Chlorinated paraffins (CPs) cannot be efficiently removed by conventional water treatment processes and are continually discharged into the aqueous environment. Ozonation can effectively remove lipophilic and persistent pollutants. However, the degradation behaviors of short-chain CPs (SCCPs), medium-chain CPs (MCCPs), and long-chain CPs (LCCPs) in wastewater during the ozonation process remained unknown. In this study, ozonation treatment achieved removal efficiencies of 61 % for SCCPs, 66 % for MCCPs, and 51 % for LCCPs from wastewater within 30 min. Approximately 147 oxidative products of SCCPs, MCCPs, and LCCPs were non-targeted identified through Ph4PCl-enhanced ionization with ultra-high performance liquid chromatography-Orbitrap mass spectrometry. These oxidation products were structurally classified into three categories: carbon chain breakage (53 products), HCl-elimination (27 products), and hydroxylation (67 products). Twenty-three di-hydroxylated CPs were newly identified among the products. Hydroxylation was the predominant pathway for SCCPs, producing di-hydroxylated SCCPs ((OH)₂-SCCPs) with a higher generation rate constant (KG = 22.28 × 10⁻² min⁻¹) compared to other products. MCCPs and LCCPs mainly underwent carbon chain breakage and hydroxylation, generating shorter carbon chain congeners, (OH)2-SCCPs, and di-hydroxylated MCCPs ((OH)2-MCCPs). The KG values of (OH)2-SCCPs (10.56 × 10-2 min-1) and (OH)2-MCCPs (12.05 × 10-2 min-1) generated from the MCCPs were the highest, and the KG values of MCCPs (6.49 × 10-2 min-1), SCCPs (6.27 × 10-2 min-1), and (OH)2-SCCPs (4.74 × 10-2 min-1) generated from the LCCPs were higher than those of other products. These results comprehensively clarify the oxidation efficiencies and pathways of CPs during ozonation. Future studies must explore the potential risks associated with the oxidation products.

Water Pollutants, Chemical↗
PubMed2026

Long-Term Warming Reduces Bacterial Diversity and Functional Potential in Temperate Forest Soil.

Soil microbes are key regulators of forest carbon cycling, yet how their diversity and functional potential respond to long-term warming remains poorly understood. Here, we report a five-year in situ warming experiment in a temperate forest, combining ten repeated measurements of microbial diversity and functional gene potential, as well as continuous monitoring of soil CO2 flux. We found that warming progressively reduced bacterial diversity and induced phylogenetically conserved community reorganization. Under warming, community composition shifted in a phylogenetically conserved manner. Warming generally reduced the abundance of microbial functional genes across most carbon-, nitrogen-, and phosphorus-cycling gene categories, except for genes associated with starch decomposition. Warming also altered the factors associated with soil CO2 flux: microbial diversity showed a stronger association with soil CO2 flux under long-term warming, whereas soil moisture was the dominant predictor in the control treatment. This warming-enhanced biodiversity control over soil CO2 flux was associated with shifts in microbial functional potential, particularly increases in starch-degrading genes and microbial biomass production potential. Together, our results suggest that warming can restructure microbial communities in ways that strengthen biodiversity-dependent regulation of soil carbon cycling, with implications for climate-carbon feedbacks.

Soil Microbiology↗
PubMed2026

The Association of Allergic Rhinitis with Chronic Adenotonsillar Diseases and Chronic Rhinosinusitis: A Mendelian Randomization Study.

INTRODUCTION: Allergic rhinitis (AR) has long been considered to be associated with chronic adenotonsillar disease (CATD). However, their causal relationship remains unclear. This study aims to investigate the causal relationship between AR and CATD and to examine the mediating role of chronic rhinosinusitis (CRS) in this association. METHODS: This study employed a two-sample Mendelian randomization (MR) design using genetic instrumental variable analysis. Data for allergic rhinitis (AR) were obtained from the MRC IEU OpenGWAS data infrastructure, data for chronic adenotonsillar disease (CATD) from the FinnGen biobank, and data for chronic rhinosinusitis (CRS) from the GWAS Catalog. Several MR methods were applied. In addition, a two-step MR approach was used to investigate the mediating role of CRS in the relationship between AR and CATD. RESULTS: MR analysis identified a positive correlation between AR and CATD. IVW and weighted median analyses showed significant causal effects (beta = 0.55, 95% CI: 0.26 to 0.84); p <0.001). No causal association was found between CATD and AR. AR and CRS showed a positive correlation (beta = 1.38, 95% CI: 0.78 to 1.98; p = 6.5 &#xd7; 10-6). CRS had a beta value of 0.15 (95% CI: 0.06 to 0.24; p = 0.001) for CATD. CRS mediates 37.6% of the AR to CATD pathway (mediation effect = 0.20, 95% CI: 0.04 to 0.37; p = 0.013). DISCUSSION: These findings indicate that AR may contribute to CATD risk through CRS, highlighting the need for further research to explore underlying biological mechanisms and validate these findings. CONCLUSIONS: This study suggests a positive causal relationship between AR and CATD, with CRS acting as a mediator.

Mendelian Randomization Analysis↗
PubMed2025

STT3A is essential for Wnt signaling and represents a target for cancers driven by RNF43 deficiency.

Abnormalities in the Wnt pathway are major drivers of cancer. RNF43 loss-of-function mutations are frequently detected in aggressive cancers lacking targeted therapies, underscoring the need to uncover key regulators and targets of this pathway. Using a double death trap (DDT) Wnt reporter and genome-wide CRISPR screen, we identified STT3A as an essential regulator of Wnt signaling. Genetic and pharmacological inhibition of STT3A suppressed aberrant Wnt activity caused by RNF43/ZNRF3 loss. Importantly, suppression of STT3A blocked the growth of RNF43-deficient cancer cell lines, patient-derived organoids, and spontaneous tumors. Mechanistically, STT3A regulates Wnt/&#x3b2;-catenin signaling via LRP6, but not LRP5. Glycosylation of LRP6 by STT3A is required for Wnt ligand binding. Notably, STT3A depletion displayed milder effects on bone homeostasis, as supported by phenotypes in STT3A-deficient patients. Together, this study established STT3A as a critical Wnt regulator through LRP6 glycosylation and a therapeutic target for RNF43-deficient cancers.

Humans↗
PubMed2025

The relationship between vitamin D levels and depression: a genetically informed study.

BACKGROUND: Low vitamin D (vitD) levels are consistently associated with an increased risk of depression. However, the biological mechanisms underlying this relationship and potential shared genetic overlap remain elusive. METHODS: We investigated the genetic overlap and causal relationships between depression (N&#x2009;=&#x2009;589,356) and vitD levels (N&#x2009;=&#x2009;417,580) using genome-wide association study (GWAS) summary statistics. We performed genome-wide and local genetic correlation analyses, followed by quantification of polygenic overlap variants. Shared genetic loci were identified and mapped to genes, which were further analyzed through gene expression and lifespan brain expression trajectory analyses. Bidirectional causal relationships were examined using multiple Mendelian randomization approaches. RESULTS: We observed significant negative genetic correlations (rg = -0.079) and identified genetic overlap (N&#x2009;=&#x2009;410 variants). Genes mapped to the 13 shared loci showed opposing expression patterns. Tissue- and cell-specific functional enrichment analyses revealed significant signals related to brain development, with distinct patterns emerging between fetal development and adulthood. Shared genes (TRMT61A, ITIH4, RASGRP1, CTNND1, HERC1, IP6K1, FURIN ESR1, ZMYND and GRM5) exhibited notable expression variation in the brian throughout the lifespan, aligning with functional enrichment findings. CONCLUSIONS: Our findings elucidate the shared biological mechanisms underlying the relationship between vitD and depression, suggesting that vitD play an important role in the development of depression through altered early neurodevelopmental processes.

Humans↗
PubMed2025

Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy.

Young human de novo genes, recently emerging from non-coding regions, are expected to contribute to human-specific traits and diseases. However, systematic explorations of this connection have been lacking. Here, we report 37 recently originated de novo genes in humans, with their evolution and characteristics defined within an updated genomic context. The expression of these genes is significantly upregulated and temporospatially expanded in tumors, partially associated with extrachromosomal DNA amplification. Depletion of 57.1% of these genes suppresses tumor cell proliferation, underscoring their roles in tumorigenesis. As a proof of concept, we developed mRNA vaccines expressing ELFN1-AS1 and TYMSOS-young genes specifically expressed during early development but reactivated exclusively in tumors. In humanized mice, these vaccines triggered specific T cell activation and inhibited tumor growth. The antigens derived from these genes are immunogenic and capable of eliciting antigen-specific T cell activation in colorectal cancer patients. These findings underscore young human de novo genes as neoantigens in cancer immunotherapy.

Humans↗
PubMed2025

Genome-Wide Silencer Screening Reveals Key Silencer Modulating Reprogramming Efficiency in Mouse Induced Pluripotent Stem Cells.

The majority of the mouse genome is composed of non-coding regions, which harbor numerous regulatory sequences essential for gene regulation. While extensive research focuses on enhancers that activate gene expression, the role of silencers that repress gene expression remains less explored. In this study, the first genome-wide identification of silencers in the mouse genome is conducted. In mouse embryonic fibroblasts (MEFs) and embryonic stem cells (mESCs), 89&#xa0;596 and 115&#xa0;165 silencers are identified, respectively. These silencers are ubiquitously distributed across the genome and are predominantly associated with low-expression genes. Additionally, these silencers are mainly cell-specific and function by binding to repressive transcription factors (TFs). Further, these silencers are notably enriched with the histone modification H3K9me3. It is observed that the transformation between dual-function silencers and enhancers is correlated with intracellular transcription factor concentrations, accompanied by changes in epigenetic modifications. In terms of biological effects, we have identified silencers that can enhance the induction efficiency of MEFs and influence the pluripotency of mESCs. Collectively, this work offers the first comprehensive silencer landscape in the mouse genome and provides strong evidence for the role of silencers in the induction of induced pluripotent stem cells (iPSCs).

Animals↗
PubMed2024

Diverse phenotypes and fertility outcomes of patients with androgen insensitivity syndrome in a Chinese family harboring identical AR gene variant.

BACKGROUND: Androgen insensitivity syndrome (AIS) is a rare genetic disorder characterized by resistance to androgens, mainly due to mutations in the androgen receptor (AR) gene. It can manifest as complete AIS, partial AIS and mild AIS. While there have been studies linking specific AR gene mutations to AIS phenotypes, different clinical AIS phenotypes are also reported in patients with the same AR gene mutation. So far, the precise correlations between phenotypes and genotypes remain incompletely understood. METHODS: We conducted a thorough investigation involving four patients diagnosed with different types of AIS from a single Chinese family. Clinical manifestations, laboratory examinations, and fertility outcomes were well-documented. Furthermore, we performed genetic sequencing to detect possible pathogenetic variants. RESULTS: Whole exome sequencing identified a hemizygous missense variant (c.2263T&#x2009;>&#x2009;C; p.Phe755Leu) of AR gene in all four affected patients with different degrees of undermasculinisation and heterogeneous spermatogenesis. The proband, diagnosed with partial AIS, opted for treatment with donated sperm due to non-obstructive azoospermia, while their older sibling, diagnosed with complete AIS, was raised as a girl. His two maternal uncles were both diagnosed with mild AIS, the older uncle fathered two girls naturally, whereas the younger uncle utilized assisted reproductive technology to conceive a boy because of severe oligoasthenozoospermia. CONCLUSION: Our study first identified the same AR variant (c.2263T&#x2009;>&#x2009;C;p.Phe755Leu) in four affected patients displaying highly diverse phenotypes of AIS and fertility outcomes, thereby significantly expanding the phenotypic spectrum of AIS. Notably, we presented a clear insight into different fertility outcomes of AIS patients with identical AR (c.2263T&#x2009;>&#x2009;C;p.Phe755Leu) variant, which provided reliable evidence that males harboring this variant may obtain biological offspring naturally or in combination with assisted reproductive technology. Furthermore, our study underscored the potential role of androgen concentration in shaping the phenotypic diversity of AIS, warranting further investigation.

Adult↗