Biomedical subjects

Chen Wang

Publications and source records attributed to Chen Wang.

11 recordsLinked to original sources

PubMed2026

Clinical and genetic analysis of a family with 16p11.2 microduplication syndrome and variable multisystem manifestations.

16p11.2 microduplication syndrome (OMIM #614671) is a pathogenic recurrent copy-number gain at the 16p11.2 locus and is associated with variable expressivity across neurodevelopmental, growth, and medical phenotypes. Gastrointestinal symptoms have been reported in carrier cohorts, but detailed documentation of gastrointestinal motility and neuromuscular findings remains limited. We performed clinical and genetic analyses in a multigenerational family in which the proband (III1) presented with limb muscle pain, exercise intolerance, and chronic gastrointestinal symptoms. Next-generation sequencing (NGS), low-pass whole-genome sequencing (lpWGS)-based CNV analysis, Sanger sequencing, and qPCR validation identified a 0.8 Mb microduplication at 16p11.2 (BP4-BP5), involving 44 genes including TBX6, inherited from the mother (II2). The proband's clinical manifestations included developmental delay, pointed chin, low body mass index, gastrointestinal dysfunction (chronic abdominal pain, diarrhea, esophageal motility disorder, and rectal prolapse), forward-leaning gait, mild scoliosis, and limb muscle atrophy with inflammatory muscle involvement. Four family members (II2, III1, III2, and III4) carried the microduplication, but their available clinical features varied in severity and system involvement. The proband's twin brother (III2) had left ear deafness and epilepsy, individual II2 had blindness from cone-rod dystrophy, and III4 showed more pronounced scoliosis. This family provides a detailed clinical and genetic description of 16p11.2 microduplication carriers with prominent gastrointestinal motility and neuromuscular manifestations, thereby enriching the clinical characterization of this recurrent CNV and supporting substantial intrafamilial phenotypic heterogeneity.

16p11.2 microduplication syndrome↗

PubMed2026

Toward real-time quantification of driving risks: a systematic review and research agenda of risk field theory.

In complex traffic systems, driving risk often evolves in a continuous and progressive manner prior to crash occurrence. How to effectively represent and analyze such latent risk states remains a central challenge in traffic safety research. In recent years, risk field-based approaches have introduced spatial and spatiotemporal continuous modeling paradigms, providing new perspectives for characterizing the distribution of traffic risk and its dynamic evolution. Motivated by the rapid growth of this research area and the lack of a systematic synthesis, this paper presents a comprehensive review of studies applying risk field theory to driving safety and traffic risk analysis. Following the PRISMA guidelines, relevant literature was collected through multi-database searches and analyzed using a combination of bibliometric analysis and qualitative review. The review systematically summarizes the theoretical foundations, modeling elements, data sources, analytical methods, and application domains of risk field-related research. Particular attention is given to studies that conceptualize traffic risk as a continuous field, complemented by a broader review of traffic risk factor literature to identify key elements and analytical dimensions involved in risk field modeling. On this basis, the paper synthesizes research progress in major application areas, including traffic safety state representation, driving behavior analysis, traffic conflict assessment, and autonomous driving and human-machine cooperative systems. Differences and commonalities among existing studies are compared in terms of modeling strategies, data support, and application scenarios. Through this systematic review, the paper clarifies the main research themes and methodological trends of risk field-based studies, providing a structured framework for understanding the evolution and application of this approach and offering methodological insights for risk perception modeling and safety-oriented decision support in intelligent transportation systems (ITS).

Humans↗

PubMed2026

Inherited Susceptibility to Urinary Tract Infections from Kidney Papilla to Bladder.

Urinary tract infections (UTIs) are traditionally viewed as environmentally driven, yet their inherited susceptibility remains largely unexplored. We conducted a cross-biobank genome-wide association study of recurrent UTIs in 1,860,836 individuals (213,869 cases and 1,646,967 controls). We identified 36 genetic susceptibility loci and performed tissue-based multi-omic mapping to prioritize candidate causal genes. UTI risk alleles preferentially modulated epithelial gene expression in kidney and bladder, converging on urinary epithelia structure and function. PSCA, encoding a secreted epithelial surface protein, emerged as the strongest candidate under genetic control; the gene product is constitutively secreted into the urine from kidney papilla and bladder epithelia, binds uropathogenic E. coli, and inhibits bacterial growth in vitro. Our findings define the polygenic architecture of UTIs and highlight the critical role of uroepithelial surface defenses, providing a new framework for host-directed, non-antibiotic interventions.

Journal Article↗

PubMed2026

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I²=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I²=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I²=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I²=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans↗

PubMed2026

Insights into iron-enhanced denitrification coupled with antibiotic resistant genes control in biochar-based biofiltration systems.

In biofiltration (BF) systems, biochar can enhance pollutant removal by promoting biofilm formation. Its abundant pore structure can also sequester antibiotics away from microbial cells, thereby reducing its bioavailability and accumulation of antibiotic resistance genes (ARGs). However, dense biofilms favor horizontal ARG transfer, especially among denitrifying bacteria, which are prone to stress under low influent C/N conditions. In this study, a strategy combining iron minerals was proposed to alleviate the ARG accumulation in BF systems. Compared with magnetite, goethite and siderite released Fe2+ through microbial dissimilatory iron reduction and chemical dissolution respectively, thereby driving iron‑autotrophic denitrification and enhancing the activity of electron‑transfer mediators (cytochrome c and Fe-S proteins). As a result, the level of nitrosative stress was reduced with significant downregulation of related genes (hmp, hcp, norR, and etc.), which was a driving force for conjugative transfer of ARGs. Specifically, the excessive accumulation of tryptophan and shortage of methionine were thus alleviated, which contributed to the regulation of global repressor gene expression and the mitigation of ARG conjugative transfer. With the combination of goethite or siderite in BF systems, the abundance of resistance genome in biofilm exhibited a reduction of 52.68 ± 3.80% and 41.26 ± 4.20%, respectively, which could effectively reduce the environment-ecological risk of antibiotic and ARGs.

Denitrification↗

PubMed2026

ZrO₂@C-based colorimetric/photothermal dual-mode immunosensor coupled with a novel monoclonal antibody for quantification of Aspergillus ochraceus biomass.

Aspergillus ochraceus contaminates agricultural products and produces nephrotoxic, carcinogenic ochratoxin A (OTA), posing severe food safety hazards. A dual-signal lateral flow immunochromatographic assay (dLFIA) based on ZrO₂@C nanoprobes was established for quantitative detection of A. ochraceus biomass. A novel monoclonal antibody (mAb 4B4) was prepared as the capture antibody to immobilize A. ochraceus mycelial lysate antigen on the test line, and a rabbit polyclonal antibody (pAb G2801) as the detection antibody to modify ZrO₂@C composites (synthesized via UiO-66 pyrolysis) into 200 nm colorimetric/photothermal nanoprobes. This dLFIA achieved limits of detection of 0.164 μg/mL (colorimetric) and 0.517 μg/mL (photothermal). This efficient and reliable method allows quantitative analysis of A. ochraceus biomass, which is suitable for routine monitoring of fungal contamination in agro-food matrices.

Antibodies, Monoclonal↗

PubMed2026

Discovery and Engineering of a Rat Endogenous Retrovirus Reverse Transcriptase for Efficient Prime Editing.

CRISPR-based prime editors (PEs) install precise edits into genomic DNA without generating double-strand breaks. Their editing efficiency is highly dependent on reverse transcriptases (RTs), but efficient RT candidates remain limited. Here, we identified 19 novel active RTs by screening 558 candidates. Among them, RERV-RT, derived from Rattus norvegicus, exhibited the highest activity. Through structure-guided engineering and deep mutational scanning, we developed an optimized variant, enRERV-RT, which outperforms conventional M-MLV-RT-based PE systems by 1.20-fold in mammalian and plant cells, and by 1.88-fold at hard-to-edit loci, while enabling precise multiplex editing of functionally relevant genes. Additionally, we developed a high-throughput platform, TRAP-seq-PE, to systematically evaluate prime editor performance. Across diverse mutation types, we found that PE systems based on enRERV-RT exhibited higher editing efficiencies than those based on M-MLV-RT. Collectively, our work establishes a versatile, high-efficiency PE system, thereby facilitating advances in clinical gene therapy and precise crop breeding.

Animals↗

PubMed2026

Discovery and validation of a prognostic SPP1/PLAU signature in HPV-negative oropharyngeal squamous cell carcinoma.

BACKGROUND: This study aimed to identify and validate robust prognostic biomarkers for oropharyngeal squamous cell carcinoma (OPSCC), with a specific focus on the high-risk HPV-negative subtype. METHODS: Integrated bioinformatics analysis was performed on transcriptomic data from four GEO datasets (n = 418 samples). Differentially expressed genes (DEGs) were identified, and a protein-protein interaction (PPI) network was constructed for the most dysregulated genes. Key modules were analyzed via survival analysis and multivariate Cox regression. The top candidate genes were validated at the protein level using immunohistochemistry (IHC) in an independent cohort of 304 OPSCC patients. RESULTS: A 33-gene module related to extracellular matrix organization showed significant prognostic association. It stratified patients into high- and low-risk groups with markedly different overall survival (HR = 2.71, p < 0.001). From this module, SPP1 and PLAU were identified as independent prognostic factors through multi-step screening. Both genes were significantly overexpressed in tumors (approximately 20-fold and 10-fold, respectively, p < 0.001), with high expression strongly correlated with advanced tumor stage (p < 0.01) and, notably, the HPV-negative subtype (p < 0.001). In survival analysis, high expression of either SPP1 or PLAU was associated with poorer overall survival (SPP1: p < 0.001; PLAU: p < 0.001) and progression-free survival (p < 0.001). IHC validation confirmed high protein expression in 69.7% (SPP1) and 54.8% (PLAU) of cancer tissues. A prognostic nomogram integrating the SPP1/PLAU signature with clinical variables was constructed with strong predictive accuracy (C-index = 0.75). CONCLUSION: The SPP1/PLAU dual-gene signature is a robust and independent prognostic biomarker for OPSCC, with particular clinical utility for stratifying high-risk HPV-negative patients.

Humans↗

PubMed2025

Disassembly activates Retron-Septu for antiphage defense.

Retrons are antiphage defense systems that produce multicopy single-stranded DNA (msDNA) and hold promise for genome engineering. However, the mechanisms of defense remain unclear. The Retron-Septu system integrates retron and Septu antiphage defenses. Cryo-electron microscopy structures reveal asymmetric nucleoprotein complexes comprising a reverse transcriptase, msDNA (a hybrid of msdDNA and msrRNA), and two PtuAB copies. msdDNA and msrRNA are essential for assembling this complex, with msrRNA adopting a conserved lariat-like structure that regulates reverse transcription. Notably, the assembled Retron-Septu complex is inactive, with msdDNA occupying the PtuA DNA binding site. Activation occurs upon disassembly, releasing PtuAB, which degrades single-stranded DNA to restrict phage replication. This "arrest-and-release" mechanism underscores the dynamic regulatory roles of msDNA, advancing our understanding of antiphage defense strategies.

Cryoelectron Microscopy↗

PubMed2025

Comparative Genomic Screening Identifies Developmental Constraint Loci Underscoring the Phenotypic Evolution of Syngnathids.

Seahorses and their relatives (syngnathids) exhibit remarkable diversity in morphology and function, characterized by their distinctive body shapes and specialized feeding mechanisms. Despite recent advances in uncovering the genetic basis of some traits, the genotype-phenotype map in syngnathids remains incomplete. In this study, we employed forward-genomic approaches and developed a method to enrich for human disease amino acid loci at a genomic scale. Our aim was to identify genetic loci associated with fin size reduction, tooth loss, and spinal curvature in syngnathids. Intriguingly, we identified a convergent amino acid change in the lat4a gene shared by syngnathids and some flying fishes, with in vitro analysis confirming its role in fin size evolution in both lineages. While genes critical for tooth development are conserved in syngnathids, the absence of key regulatory elements, such as pitx2, likely contributes to tooth loss. Additionally, we implicated col6a3 in spinal curvature development in seadragons. These findings reveal novel genetic signatures and developmental constraints underlying syngnathid diversity, demonstrating the utility of comparative genomics and targeted gene enrichment in exploring vertebrate evolution.

Animals↗

PubMed2025

PSIA: A Comprehensive Knowledgebase of Plant Self-incompatibility.

Self-incompatibility (SI) is an important genetic mechanism in angiosperms that prevents inbreeding and promotes outcrossing, with significant implications for crop breeding, including genetic diversity, hybrid seed production, and yield optimization. In eudicots, SI is typically governed by a single S-locus containing tightly linked pistil and pollen S-determinant genes. Despite major advances in SI research, a centralized, comprehensive resource for SI-related genomic data remains lacking. To address this gap, we developed the Plant Self-Incompatibility Atlas (PSIA), a systematically curated knowledgebase providing an extensive compilation of plant SI, including genomic resources for SI species, S gene annotations, molecular mechanisms, phylogenetic relationships, and comparative genomic analyses. The current release of PSIA includes over 500 genome assemblies from 469 SI species. Using known S genes as queries, we manually identified and rigorously curated 3700 S genes. PSIA provides detailed S-locus information from assembled genomes of SI species and offers an interactive platform for browsing, BLAST searches, S gene analysis, and data retrieval. Additionally, PSIA serves as a unique platform for comparative genomic studies of S-loci, facilitating exploration of the dynamic processes underlying the origin, loss, and regain of SI. As a comprehensive and user-friendly resource, PSIA will greatly advance our understanding of angiosperm SI and serve as a valuable tool for crop breeding and hybrid seed production. PSIA is freely available at http://www.plantsi.cn.

Self-Incompatibility in Flowering Plants↗