Biomedical subjects

Xin Yang

Publications and source records attributed to Xin Yang.

11 recordsLinked to original sources

PubMed2026

Phylogeographic epidemiology of Dabie bandavirus in East Asia: divergent transmission networks and genotype‑linked clinical severity.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (SFTSV), exhibits geographically decoupled incidence and fatality patterns across East Asia. We aimed to elucidate the distinct ecological drivers and phylogeographic dynamics underlying this inland-coastal epidemiological divergence. METHODS: Integrating 1820 high-quality global genomes of SFTSV with well-characterized clinical cohorts (936 patients) and nationwide surveillance data (27,457 cases) from China, we constructed a comprehensive analytical framework. Ecological modeling, Bayesian phylogeography, and genotype-phenotype association analyses were employed to trace the evolutionary trajectories and clinical implications of the virus. RESULTS: A pronounced "inland-high-incidence vs. coastal-high-fatality" pattern of SFTS was identified. The incidence of SFTS exhibited divergent sensitivities to meteorological factors; inland transmission was sensitive to thermal fluctuations, whereas coastal dynamics were constrained by a sunshine threshold (> 200 h/month). In contrast, spatial divergence in clinical severity correlated with the distribution of regional viral genetic structures. Inland regions mainly co-circulated genotypes A, C, and D, while coastal regions were dominated by genotype B. Zhejiang province was identified as a genetic hub with significantly higher recombination frequencies than inland regions (11.0% vs. 3.5%, P < 0.001). Bayesian phylogeographic inference indicated frequent lineage exchange of Zhejiang province in China with the Republic of Korea and Japan. Clinically, genotypes B and D were associated with elevated mortality in coastal and inland regions, respectively, suggesting that the severe coastal phenotype is shaped by its genotype B-dominated structure. Additionally, the RdRp-N828S mutation emerged as a robust molecular correlate of fatal outcomes, warranting further functional validation. CONCLUSIONS: Divergent meteorological factors and plausible maritime transmission networks may underlie the geographically decoupled epidemiology of SFTS. These findings highlight that risk assessment must extend beyond incidence alone and provide a phylogeographically informed framework for targeted surveillance and genotype-specific interventions in high-risk hotspots.

Humans↗

PubMed2026

Mechanism of Action of Hedyotis diffusa Extract in a Rat Model of Acute Lung Injury Based on Transcriptomic Analysis.

OBJECTIVE: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF-α interleukin-1β IL-1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of -14.74, -14.92, -17.58, -23.04, and -16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively. CONCLUSIONS: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.

Hedyotis diffusa↗

PubMed2026

Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke.

Stroke remains a leading cause of long-term neurological disability worldwide, largely due to irreversible neuronal loss and the limited regenerative capacity of the adult mammalian brain. Neural stem cells (NSCs) in the adult brain possess the potential to generate new neurons after injury, yet the molecular mechanisms regulating their neuronal differentiation following ischemic insult remain incompletely understood. Here, integrating single-cell multi-omics analyses with spatial transcriptomics, we systematically delineated cell type-specific spatiotemporal dynamics in the striatum of a mouse model of ischemia-reperfusion injury. We identified Neurensin 1 (Nrsn1) as a gene markedly upregulated during NSC-derived neuronal differentiation in the recovery phase. Mechanistically, Foxa2 directly activates Nrsn1 transcription, whereas Nrsn1 promotes neuronal differentiation by facilitating the nuclear translocation of the chromatin-remodeling factor Smarcc1 in vitro. In vivo, both endogenous NSCs and transplanted NSCs overexpressing Nrsn1 significantly enhanced neuronal regeneration and improved functional recovery in mice subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Collectively, these findings identify Nrsn1 as a key regulator of NSC neuronal differentiation and uncover a Nrsn1-Smarcc1 coupling mechanism that promotes neural regeneration after ischemic brain injury, highlighting a potential molecular target for strategies aimed at enhancing post-stroke recovery.

Foxa2↗

PubMed2026

Ocular Nystagmus as the Initial Presenting Feature in a Patient with Complete CLTC Deletion: Expanding the Genotype-Phenotype Spectrum of CLTC-Related Disorder.

Background: CLTC-related neurodevelopmental disorder is a rare condition primarily characterized by global developmental delay (GDD) and intellectual disability (ID). To date, approximately 41 cases involving CLTC gene alterations have been reported. We present the first individual with a complete deletion of the CLTC gene. Methods: The proband is a male from a non-consanguineous family, presenting with congenital nystagmus, hypotonia, GDD, and autism spectrum disorder (ASD). Chromosomal microarray analysis and trio exome sequencing were performed. A systematic review of previously reported CLTC variant cases was conducted to delineate the phenotypic spectrum. Results: A de novo 363-kb heterozygous deletion at 17q23.1 spanning the entire CLTC gene was identified. The systematic review confirmed GDD/ID as core features and revealed various ocular abnormalities in a subset of cases. These findings indicate that the clinical phenotype extends beyond neurodevelopment, with multi-system involvement. Conclusions: The phenotypic heterogeneity of CLTC-related disorders underscores the need for comprehensive physical examination to identify extra-neurological manifestations. Accurate diagnosis relies on integrating detailed clinical phenotyping with comprehensive genomic testing. Early, precise diagnosis facilitates multidisciplinary management, informed genetic counseling, and the establishment of long-term surveillance protocols.

Humans↗

PubMed2026

Rashless varicella-zoster virus encephalitis diagnosed by metagenomic next-generation sequencing: two case reports.

BACKGROUND: Varicella-zoster virus (VZV) can cause a range of central nervous system (CNS) infections, but early diagnosis is difficult when typical skin rash is absent. Rashless VZV encephalitis may present with nonspecific clinical, cerebrospinal fluid (CSF), and neuroimaging findings and can mimic autoimmune encephalitis, primary central nervous system lymphoma, or other disorders. We report two cases of rashless VZV encephalitis diagnosed by CSF metagenomic next-generation sequencing (mNGS), with subsequent neurological complications. CASE PRESENTATION: Case 1 was a 68-year-old man admitted with fever, seizures, and impaired consciousness. Brain magnetic resonance imaging (MRI) showed multifocal abnormal signals. CSF analysis revealed marked pleocytosis and elevated protein levels, and CSF cytology showed suspected atypical lymphocytes, leading to early consideration of autoimmune encephalitis and primary central nervous system lymphoma. CSF mNGS detected VZV, and rashless VZV encephalitis was diagnosed. The patient improved after intravenous acyclovir combined with a short course of dexamethasone. On day 45 after disease onset, follow-up MRI showed a new acute cerebral infarction adjacent to the posterior horn of the left lateral ventricle. Recurrent CSF pleocytosis and persistent protein elevation suggested possible VZV-associated vasculopathy. After repeated antiviral treatment, he improved again, and no recurrence was observed during more than 3 years of follow-up. Case 2 was a 74-year-old man admitted with fever, low back pain, vomiting, and impaired consciousness. Brain MRI showed multifocal abnormal signals, and CSF analysis revealed marked inflammatory changes. CSF mNGS detected VZV, supporting the etiological diagnosis of rashless VZV encephalitis. The patient improved after intravenous acyclovir combined with a short course of dexamethasone. On day 14 after disease onset, he developed urinary retention, impaired defecation sensation, and bilateral lower-limb weakness, suggesting possible lumbosacral nerve root or cauda equina involvement. Suspected VZV-related Elsberg syndrome was considered. His urinary and bowel dysfunction recovered at 2 months after disease onset. CONCLUSIONS: Rashless VZV encephalitis may be diagnostically challenging because early clinical, CSF, and neuroimaging findings are nonspecific. CSF mNGS can support etiological diagnosis, and careful follow-up is needed to detect delayed vascular and lumbosacral nerve root complications.

Humans↗

PubMed2026

Systematic profiling of nudivirus-like genes reveals conserved and differentiated roles in a domesticated endogenous virus.

Cotesia vestalis bracovirus (CvBV) is a type of domesticated endogenous virus (DEV) derived from ancestral nudiviruses that is integrated into the genome of the parasitoid wasp Cotesia vestalis. The CvBV proviral genome is composed of two distinct components: one encoding genes associated with virion morphogenesis and assembly, and the other harboring virulence genes that are excised, circularized, and packaged into virions. CvBV replication and particle assembly occur exclusively in the ovaries of female wasps. While prior studies have largely focused on the function of virulence genes during parasitization, the molecular mechanisms underlying CvBV replication and assembly remain poorly understood. Here, we identified 71 nudivirus-like genes in the C. vestalis genome through integrated transcriptomic and proteomic analyses. Using gene silencing and microscopy-based imaging approaches, we functionally characterized 24 key genes involved in DNA replication (helicase, integrase-1, and integrase-2), transcriptional regulation (p47, lef-5, and lef-9), capsid formation (vp39, PmV, HzNVorf9-1, HzNVorf9-2, HzNVorf106, 38k, 27b, and K425_459), envelope formation (11k, 17a-1, 35a-1, 35a-2, and K425_461), virion assembly (vlf-1, HzNVorf140-1, and HzNVorf140-2), and viral infectivity (pif-0 and vp91). Although the functions of most nudivirus-like genes are generally conserved among baculoviruses, nudiviruses, and bracoviruses, lef-5, K425_459, 11k, and vp91 appear to have undergone functional divergence relative to their homologs in baculoviruses, nudiviruses, and Microplitis demolitor bracovirus, highlighting lineage-specific adaptations in CvBV. Collectively, our work provides a molecular framework for understanding CvBV assembly and serves as a valuable resource for investigating bracovirus evolution.

Animals↗

PubMed2026

DeepPlaque: a scalable multimodal platform for Aβ pathology and cell analysis in Alzheimer's disease.

Histological analysis is essential for understanding disease pathology and the microenvironment, particularly in Alzheimer's disease (AD), characterized by beta-amyloid (Aβ) plaques that exist as diffuse, fibrillar, and core species, with distinct toxicity levels. However, accurate classification of Aβ plaque types in postmortem brain tissues and profiling of surrounding cells present significant challenges. To address these challenges, we developed "DeepPlaque", an integrated system featuring "PlaqueNet", a deep learning model for automated classification of Aβ plaque species from diverse imaging platforms. DeepPlaque includes automated workflows for cellular phenotyping and proteomic profiling through targeted laser microdissection. PlaqueNet achieves expert-level accuracy (AUC > 90%) in classifying the 3 major Aβ plaque species, supporting consistent and large-scale annotation. By integrating spatial cellular phenotyping with laser microdissection, DeepPlaque enables high-throughput proteomic analysis of Aβ plaque niches, revealing that microglia are more abundant around core and fibrillar Aβ plaques, with increased expression of apolipoprotein E and amyloid precursor protein in core Aβ plaques. This customizable platform enhances the molecular and cellular characterization of Aβ plaque-associated environments, providing critical insights into AD pathology.

Alzheimer Disease↗

PubMed2026

Changes of DNA methylation and gene expression profile in placental villi and chorioamniotic membranes under preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication with elusive pathogenesis. Although epigenetic dysregulation is implicated, its layer-specific placental roles are poorly defined. This study aimed to identify shared and layer-specific epigenetic alterations in PE by profiling DNA methylation and gene expression in placental villi (PV) and chorioamniotic membranes (CAM). RESEARCH DESIGN AND METHODS: PV and CAM samples were collected from 7 normal and 8 PE pregnancies, and three public DNA methylation datasets (GSE98224, GSE44667, GSE75196) were integrated. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified based on whole-genome methylation and transcriptome sequencing. Layer-specific and shared gene sets were identified by cross-analysis, with functional annotation using Gene Ontology (GO). RESULTS: EM-seq revealed a hypermethylation-dominant, tissue-specific methylation landscape in PE placentas. Cross-tissue comparison identified shared DMGs between the two layers, including nine key genes consistently altered in public datasets. Integrated analysis in PV further identified 22 co-dysregulated genes, enriched in thermoregulation, maternal-fetal immunity, signal transduction, and cell differentiation. CONCLUSIONS: This study elucidates the shared and layer-specific dysregulation of gene networks at methylomic and transcriptomic levels in PE placenta. Comparing PV and CAM highlights placental epigenetic heterogeneity and dysfunction, offering novel clues for mechanistic research and layer-targeted therapies.

Humans↗

PubMed2026

KLF5 promotes proliferation, migration, and autophagy-/EMT‑associated molecular changes in lens epithelial cells via transcriptional activation of THBS1 in traumatic cataract.

PURPOSE: Traumatic cataract is a common blinding eye disease after ocular trauma, and its pathogenesis is closely related to lens epithelial cell dysfunction, while the definite molecular regulatory mechanism between upstream transcription factor and downstream target gene remains poorly clarified. This study aimed to clarify the role and molecular mechanism of the krüppel-like factor 5 (KLF5)/ thrombosponin 1 (THBS1) axis in regulating proliferation, migration, epithelial-mesenchymal transition and autophagy of lens epithelial cells in traumatic cataract, and to explore its potential clinical therapeutic value. METHODS: The GSE295383 dataset in the gene expression omnibus (GEO) database was downloaded, and the differentially expressed genes (DEGs) were screened by linear models for microarray data (limma) package of R language. Combined with Weighted gene co-expression network analysis (WGCNA), the gene co-expression network was constructed and the key modules were screened. Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) combined with human transcription factor target (hTFtarget) and JASPAR databases were used to predict the upstream transcription factors of THBS1. Subsequently, SRA01/04 cells were induced with transforming growth factor-beta 2 (TGF-β2) to construct a cataract cell model. RESULTS: THBS1 and KLF5 were highly expressed in LECs exposed to TGF-β2. KLF5 could activate THBS1 transcription by binding to THBS1 promoter - 174 to -165 sites. Knockdown of THBS1 inhibited TGF-β2-induced viability, proliferation, migration, and altered the expression of epithelial-mesenchymal transition (EMT)- and autophagy-related markers in LECs. Knockdown of KLF5 downregulated THBS1 expression and produced a similar inhibitory effect, while overexpression of THBS1 reversed the effect of KLF5 knockdown. CONCLUSIONS: This study demonstrated that KLF5 promoted the proliferation, migration, and EMT‑associated molecular changes of LECs in traumatic cataract through transcriptional activation of THBS1, and regulated the expression of autophagy‑related markers in LECs, suggesting that KLF5/THBS1 axis might be a potential target for the treatment of traumatic cataract.

Cataract↗

PubMed2025

Coordinated regulation of glutathione S-transferases confers metabolic flexibility in multi-insecticide-resistant Frankliniella occidentalis (Pergande).

INTRODUCTION: The evolution of multi-insecticide resistance in insect pests threatens global food security. Although glutathione S-transferases (GSTs) are implicated in detoxification, the coordinated mechanism by which specific gene subfamilies interact to confer broad-spectrum resistance remains inadequately characterized. OBJECTIVE: To dissect the functional allocation and cooperation of GST subfamilies in multi-insecticide-resistant strains of Frankliniella occidentalis. METHODS: We integrated comparative genomics (20 GST genes cloned), transcriptomics (qRT-PCR), RNAi-mediated silencing, molecular docking (AutoDock Vina), and in vitro metabolism assays (UPLC-MS/MS) across susceptible and resistant thrips strains. RESULTS: The two resistant strains (NIL-R and FS-R) exhibited moderate to high resistance to five insecticides (chlorfenapyr, emamectin benzoate, spinetoram, spinosad, and thiamethoxam), accompanied by significantly elevated GSTs activity. Phylogenetic analysis indicates that GSTs include 10 conserved delta and 7 diverse sigma members. The sigma subfamily has undergone a marked expansion due to gene duplication. Delta (FoGSTd1, d4, and d9) and sigma (FoGSTs1, s2, and s6) genes were significantly up-regulated in the resistant strains. RNAi showed specialized functional allocation among GSTs: delta GSTs mediated resistance to spinosad and chlorfenapyr, sigma GSTs were responsible for thiamethoxam resistance, and notably, cooperation between these subfamilies contributed to resistance against emamectin benzoate and spinetoram. Molecular docking and in vitro metabolism assays of FoGSTd9 and FoGSTs1 proteins further supported the functional allocation and cooperative roles of GST subfamilies. CONCLUSION: Our results indicate that F. occidentalis may coordinate GST subfamilies to achieve metabolic flexibility in response to multi-insecticide pressure. This survival strategy, mediated by mechanistic functional allocation and cooperative interactions among subfamilies, may contribute to energy conservation and reduced adaptive costs. Disruption of this coordinated mechanism represents a potential approach for overcoming resistance in agricultural pest populations.

Animals↗

PubMed2025

A One Health perspective: Genomic insights into temporal trends of antimicrobial resistance and zoonotic transmission risks in Escherichia coli from human and swine.

Antimicrobial resistance (AMR) poses a significant challenge within the One Health framework. By integrating genomic data from 824 E. coli isolates obtained from 22 swine farms in southwestern China with 8432 publicly available genomes from human and swine sources, this study provides comprehensive insights into the temporal trends and divergence of AMR in human and swine E. coli populations, the risk of AMR transmission from swine to human, and the evolutionary mechanisms underlying the human adaptation of ST2 strains. The results revealed an overall increase in AMR until approximately 2016, followed by a subsequent decline. However, resistance to tetracyclines, quinolones, and phenicols continues to exhibit an upward trend, highlighting the urgency of enhancing regulatory measures targeting these drugs. Horizontal gene transfer play pivotal roles in shaping distinct AMR profiles in human and swine strains. ST2 E. coli was identified as a major carrier of AMR in both human and swine, and also served as the primary reservoir of blaNDM-5 within the human-associated lineage. During evolution, ST2 E. coli underwent significant genetic changes, including the enrichment of blaNDM-5 and remodeling of virulence factors, facilitating its transition from a generalist lineage colonizing both human and swine to a human-adapted lineage.

Humans↗