Biomedical subjects

Chen Zhang

Publications and source records attributed to Chen Zhang.

9 recordsLinked to original sources

PubMed2026

Multidimensional GWAS analyses on longitudinal phenotypes reveal candidate genes regulating multi-stage egg production traits in Wannan yellow chicken.

Egg production performance directly determines the economic viability of indigenous chicken breeding. However, the genetic regulation of multi-stage egg production traits remains difficult to characterize due to their complex and dynamic nature. Here, we integrated a multidimensional GWAS framework, including single-trait GWAS, multi-trait GWAS (MTAG), and longitudinal trajectory-based GWAS (TrajGWAS), to identify stage-specific and shared genetic effects underlying egg production traits in Wannan yellow chickens (WNY). Whole-genome sequencing of 354 WNY hens (10× depth) and quality control yielded 14,253,816 SNPs for analysis. Selective sweep analyses comparing red jungle fowl, commercial layers, and WNY identified a genomic region containing IGF1 under significant selection pressure. Single-trait GWAS identified SNPs 4_57990480 (BMPR1B) and 17_370912 (LOC112531479) associated with egg production across three laying stages (21-30, 31-40, and 21-40 weeks). MTAG further identified loci 8_4336468 (FASLG) and 21_654726 (CHD5) with shared effects across the laying period, whereas TrajGWAS revealed longitudinal associations involving PRKG1 and identified dynamic loci associated with clutch traits, including GRID1. For clutch traits, stage-specific loci were detected for average clutch size (ACS) and maximum clutch size (MCS), including SNP 8_8542036 at 21-30 weeks, PROK1 at 31-40 weeks, and CUL5, ALKBH8 across the entire laying period. These results demonstrate that integrating complementary GWAS strategies improves the resolution of genetic architecture underlying egg production traits by capturing trait-specific, shared, and stage-dependent genetic effects. The identified GWAS loci and selective-sweep candidate regions provide insights into the genetic architecture of egg production traits and breed differentiation.

Egg production↗

PubMed2026

A Novel Homozygous Mutation in ARL2BP Causes Multiple Morphological Abnormalities of the Flagella and Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) and multiple morphological abnormalities of the sperm flagella (MMAF) frequently co-occur in male infertility. However, the genetic basis of this syndromic presentation remains unclear. Using whole-exome sequencing, we identified a novel homozygous ARL2BP splice-site mutation (c.294-2A>G) in a 23-year-old infertile male from a consanguineous family who presented with syndromic PCD and MMAF. This variant causes aberrant pre-mRNA splicing and triggers nonsense-mediated mRNA decay, resulting in the complete absence of ARL2BP protein expression. Transmission electron microscopy revealed extensive disorganization of flagellar axonemes with consistent central pair (CP) microtubule depletion and disorganization of peripheral doublets. Immunofluorescence confirmed a severe deficiency of the CP protein SPAG6 in the sperm flagella. Notably, the patient presented without retinal symptoms. Given that ARL2BP-related retinitis pigmentosa generally emerges during the third decade, long-term ophthalmological follow-up is essential to detect delayed-onset retinal degeneration. In conclusion, these findings confirm ARL2BP as a causative gene for both PCD and MMAF, expanding the genotypic and phenotypic spectrum of ciliopathies.

Humans↗

PubMed2026

Extensive pneumocephalus in a fatal central nervous system infection caused by NDM-1-producing carbapenem-resistant Klebsiella pneumoniae: a case report.

BACKGROUND: Central nervous system (CNS) infections caused by New Delhi metallo-β-lactamase-1 (NDM-1)-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) are rare but associated with extremely high mortality because of extensive antimicrobial resistance and poor blood-brain barrier (BBB) penetration. To the best of our knowledge, there have been no published reports of pneumocephalus associated with infection caused by NDM-1-producing K. pneumoniae. CASE PRESENTATION: We report an 18-year-old woman who developed bloodstream infection and metastatic CNS infection following severe thoracoabdominal crush injury. Serial cerebrospinal fluid (CSF) cultures repeatedly yielded NDM-1-producing CRKP despite multiple adjustments of antimicrobial therapy. Retrospective whole-genome sequencing demonstrated that blood and CSF isolates belonged to the same clonal lineage carrying the blaNDM-1 gene on an IncX3 plasmid, confirming hematogenous dissemination. Serial cranial computed tomography revealed progressive diffuse cerebral edema and extensive pneumocephalus in the absence of skull fracture or neurosurgical intervention. Persistent microbiological failure was mainly attributed to the combination of NDM-1-mediated multidrug resistance and inadequate CNS antibiotic exposure, which ultimately led to the patient's death. CONCLUSION: This case illustrates the devastating clinical course of NDM-1-producing CRKP CNS infection and identifies extensive pneumocephalus as a rare but potentially fatal complication. It emphasizes the importance of early molecular diagnosis, repeated CSF microbiological assessment, optimization of antimicrobial regimens with adequate CNS penetration, and implementation of effective infection-control strategies. The case also highlights the urgent need for novel therapeutic approaches against metallo-β-lactamase-producing pathogens.

blaNDM-1 gene↗

PubMed2026

A three-metabolite microbiota-associated signature for early risk stratification of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes and long-term metabolic and cardiovascular risk. However, oral glucose tolerance testing at 24-28 gestational weeks limits early risk stratification. Gut microbiota-associated metabolites may reflect early metabolic abnormalities, including those relevant to cardiometabolic health, but robust early-pregnancy biomarkers remain limited. METHODS: We conducted a multicenter nested case-control and prospective study involving 2,693 pregnant women. Untargeted metabolomics and metagenomics were integrated to identify GDM-associated metabolites and gut microbial alterations. Three consistently dysregulated metabolites, 3-hydroxydecanoic acid, γ-Glu-Leu, and propionic acid, were quantified by targeted LC-MS/MS. Candidate algorithms were compared using repeated 10-fold cross-validation, and a final generalized linear model was externally and prospectively validated. RESULTS: Women who later developed GDM showed an adverse early-pregnancy metabolic profile, including higher BMI, triglycerides, and platelet count. Untargeted metabolomics identified 14 persistently altered metabolites enriched in energy, oxidative stress, and amino acid metabolism pathways. Metagenomics revealed taxonomic restructuring and coordinated microbiota-metabolite associations. The three-metabolite model achieved AUCs of 0.838 (95% CI, 0.791-0.885) in training, 0.840 (95% CI, 0.769-0.911) in internal validation, 0.955 (95% CI, 0.925-0.985) and 0.917 (95% CI, 0.875-0.958) in two external cohorts, and 0.969 (95% CI, 0.937-1.000) in the prospective cohort. CONCLUSION: Early microbiota-associated metabolic dysregulation is detectable before routine GDM diagnosis. This compact three-metabolite panel may support early GDM risk stratification and provides metabolic evidence relevant to broader cardiometabolic risk assessment in pregnancy.

Humans↗

PubMed2026

Noncanonical bactericidal activity of teleost type I interferon is conferred by a membrane-targeting C-terminal peptide.

Type I interferons (IFNs) are indispensable antiviral cytokines in nonspecific immunity, yet they play dual roles in bacterial infections in mammals. Recent studies have revealed a subset of strongly cationic type I IFNs possessing potent antimicrobial properties across nonmammalian vertebrates. In this study, we identified a type I IFN gene, CaIFNi, from Cromileptes altivelis that is characterized by a unique triple-disulfide bond architecture. In Vibrio harveyi-challenged models, overexpression of CaIFNi potentiated bacterial clearance capacity in tissues, whereas its knockdown exacerbated bacterial colonization, highlighting its ability to protect the host against bacterial infection in vivo. In vitro assays further confirmed that CaIFNi directly binds to and kills both gram-negative (G-) and gram-positive (G+) bacteria, which first revealed the antibacterial function of new subgroup IFNi within teleost type I IFNs. Furthermore, the α-helical peptide CaIFNi-18 derived from CaIFNi was identified as a novel antimicrobial peptide (AMP) that has broad-spectrum antibacterial efficacy against G- and G+ bacteria and membrane-targeting ability. Further mechanistic studies revealed that CaIFNi has bactericidal effects on both G- and G+ bacteria through membrane depolarization and disruption, alteration of the bacterial ultrastructure, and in vitro binding to genomic DNA. In addition, CaIFNi-18 also has significant in vivo therapeutic efficacy against bacterial infection, highlighting its great potential as an antibacterial agent. Encouragingly, the loss of antibacterial activity in the truncation mutant (rCaIFNiΔ148-165) lacking the CaIFNi-18 segment suggests that this region is essential for the bactericidal function of the full-length protein and likely acts as its core domain. Further computational simulations revealed that the deletion of the CaIFNi-18 region attenuated the interaction between the protein and the bacterial membrane. These findings not only expand the functional scope of type I IFNs beyond their canonical antiviral role but also identify their derivative CaIFNi-18 as both a promising antimicrobial candidate and the essential bactericidal domain of CaIFNi, thereby offering novel therapeutic strategies against bacterial infections in the aquaculture industry and beyond.

Animals↗

PubMed2026

[State Changes and Stability Grading of Driver Genes in Non-small Cell Lung Cancer Based on Repeated NGS Testing].

BACKGROUND: Next-generation sequencing (NGS)-based driver gene testing has become a routine component of molecular subtyping and precision therapy for non-small cell lung cancer (NSCLC). Dynamic genomic monitoring facilitates early detection of resistance-related molecular alterations and informs timely therapeutic adjustments. However, standardized criteria for evaluating the stability of serial NGS testing are currently lacking, and the applicability of NGS using formalin-fixed paraffin-embedded (FFPE) specimens for dynamic monitoring remains poorly defined. This study aims to establish a stability grading system for driver gene status alterations based on repeated NGS testing, and to provide evidence-based support for clinical repeat biopsy strategies. METHODS: Data from 1232 patients with NSCLC who underwent two or more NGS tests on FFPE tissue specimens at Beijing Chest Hospital between June 2019 and April 2026 were collected retrospectively. Patients with an interval of ≥4 months between the initial and last tests were included to ensure the representativeness of temporal analysis, resulting in a main analysis cohort of 942 patients. The Kappa consistency test was used to evaluate the state stability of nine core driver genes [epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), mesenchymal‑epithelial transition factor (MET), rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), erb‑b2 receptor tyrosine kinase 2 (ERBB2), and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA)] and to construct a five‑level grading system. Paired variant allele frequency (VAF) differences were compared using the Wilcoxon signed‑rank test. Independent influencing factors for mutation accumulation were identified by binary Logistic regression. RESULTS: The state stability of the nine genes was classified into five levels: EGFR showed high stability (Kappa=0.838), ROS1/ALK/KRAS good stability, BRAF/PIK3CA/RET moderate stability, and ERBB2 low stability, and MET showed high instability. MET exhibited the highest rate of state change (9.3%) with a raw observed agreement of 90.7%. Its Kappa value (0.172) was influenced by the low prevalence (3.7%) compression effect and should therefore be interpreted alongside the observed agreement (90.7%) and the prevalence-adjusted and bias-adjusted Kappa (PABAK). The VAF of PIK3CA increased significantly (P=0.005). T790M positivity increased from 5.8% to 10.8%, and 30 new C797S mutations were detected at the last test (13 with T790M, 17 without). The overall rate of new driver gene variants in the main cohort was 18.0%. Binary Logistic regression showed that a lower number of initial mutated genes was the only independent predictor of new variants [odds ratio (OR)=0.399, P<0.001], while sex and detection interval showed no independent association. CONCLUSIONS: A five level stability grading system for state changes of driver genes in NSCLC based on repeated NGS testing has been established. MET showed the most frequent state changes, which should be interpreted in conjunction with the prevalence effect. The VAF increase of PIK3CA is an observational finding, and its clinical significance requires further prospective validation. A lower initial mutation burden may reflect tumor clonal complexity and was associated with a higher likelihood of subsequent acquisition of new variants. FFPE based NGS is applicable for repeated testing at clinical treatment decision nodes.

Humans↗

PubMed2025

Alternative spliceosomal protein Eftud2 mediated Kif3a exon skipping promotes SHH-subgroup medulloblastoma progression.

Alternative splicing plays a pivotal role in various facets of organogenesis, immune response, and tumorigenesis. Medulloblastoma represents a prevalent childhood brain tumor, with approximately one-third classified as the Sonic Hedgehog (SHH) subgroup. Nevertheless, the contribution of alternative splicing to medulloblastoma oncogenesis remains elusive. This investigation delineated an upregulation of the spliceosomal protein Eftud2 in the SHH-subgroup medulloblastoma mouse model and human medulloblastoma patients. Targeted ablation of Eftud2 in granule precursor cells (GNPs) within the cerebellum prolonged the survival of SHH-subgroup medulloblastoma mice, indicating a putative association between Eftud2 expression and medulloblastoma prognosis. Functional assays unveiled that EFTUD2 depletion in human medulloblastoma cells significantly curtailed cellular proliferation by impeding the activation of the SHH signaling pathway. Through multi-omics sequencing analysis, it was discerned that Eftud2 influences exons 10-11 skipping of Kif3a, a kinesin motor critical for primary cilia formation. Notably, exons 10-11 skipping in Kif3a augmented human medulloblastoma cell proliferation by potentiating the transcriptional activity of Gli2. These findings underscore a robust correlation between Eftud2 and SHH-subgroup medulloblastoma, emphasizing its regulatory role in modulating downstream transcription factors through the alternative splicing of pivotal genes within the SHH signaling pathway, thereby propelling the aggressive proliferation of SHH-subgroup medulloblastoma.

Medulloblastoma↗

PubMed2025

Identification of multicohort-based predictive signature for NMIBC recurrence reveals SDCBP as a novel oncogene in bladder cancer.

BACKGROUND: Despite surgical and intravesical chemotherapy interventions, non-muscle invasive bladder cancer (NMIBC) poses a high risk of recurrence, which significantly impacts patient survival. Traditional clinical characteristics alone are inadequate for accurately assessing the risk of NMIBC recurrence, necessitating the development of novel predictive tools. METHODS: We analyzed microarray data of NMIBC samples obtained from the ArrayExpress and GEO databases. LASSO regression was utilized to develop the predictive signature. We combined gene signature and clinicopathological factors to construct a clinical nomogram for estimating NMIBC recurrence in a local cohort. Finally. the biological functions and potential mechanisms of SDCBP in bladder cancer were investigated experimentally in vitro and in vivo. RESULTS: An 8-gene signature was developed, and its efficiency for predicting NMIBC recurrence was evaluated using Kaplan-Meier and time-dependent ROC curves in both training and validation datasets. Immunohistochemical testing revealed elevated levels of ACTN4 and SDCBP in recurrent NMIBC tissues. We integrated the two proteins with clinical factors to develop a nomogram model, which showed superior accuracy compared to individual parameters. Gene Set Variation Analysis and Gene Set Enrichment Analysis unveiled SDCBP exerted cancer-promoting biological processes, such as angiogenesis, EMT, metastasis and proliferation. Experimental procedures demonstrated that silencing SDCBP attenuated cell growth, glucose metabolism and extracellular acidification rate, accompanied by decreased expression of p-AKT, p-ERK1/2, LDHA and Vimentin. CONCLUSIONS: The established 8-gene signature holds promise as a tool for predicting NMIBC recurrence, while targeting SDCBP may represent a potential strategy for delaying disease relapse.

Urinary Bladder Neoplasms↗

PubMed2016

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking.

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data.

Biological Products↗