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Xi Wang

Publications and source records attributed to Xi Wang.

4 recordsLinked to original sources
PubMed2026

A fitness advantage from the pLVPK plasmid fuels the global spread of a carbapenem-resistant hypervirulent Klebsiella pneumoniae high-risk clone: ST11-KL64.

BACKGROUND: The global emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), particularly the ST11-KL64 subclone acquiring pLVPK-like virulence plasmids, represents a critical public health threat. This study investigates the epidemiological dominance and molecular mechanisms underlying ST11-KL64's fitness advantage over KL47 variants. METHODS: We performed comparative genomic analysis on 43,722 K. pneumoniae genomes (2011-2022) from 112 countries, focusing on ST11-CRKP strains. Capsular typing (KL64 vs. KL47), virulence gene profiling (aerobactin, RmpADC), and plasmid stability analysis were conducted using Kleborate, RAST, and PlasmidFinder. Plasmid-chromosome interactions were characterized through hybrid assembly approaches. RESULTS: ST11-KL64 demonstrated rapid expansion post-2016, surpassing KL47 as China's dominant CRKP subtype (40.5% vs. 28.9%), with regional predominance in Zhejiang (62.3%) and Sichuan (58.7%) provinces. Notably, 94.8% of KL64 strains maintained intact pLVPK plasmids with high aerobactin carriage (60.5%), while KL47 exhibited frequent plasmid fusion (58.8% with IncFIB[pNDM-Mar]) or chromosomal integration (41.4%), resulting in lower virulence potential (27.3% aerobactin+). Genomic analysis revealed KL64's superior plasmid stability (71.2% gene retention vs. KL47's 43.6%) and clinical correlation with severe outcomes (OR = 2.34, 95%CI 1.67-3.28). CONCLUSION: The ST11-KL64 subclone's epidemiological success stems from stable pLVPK plasmid maintenance, enabling simultaneous carbapenem resistance and hypervirulence. These findings highlight the urgent need for genomic surveillance targeting plasmid-mediated virulence in CRKP outbreaks, particularly in critical care settings where horizontal gene transfer may accelerate strain evolution.

Klebsiella pneumonia↗
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

Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.

ADAR1 converts adenosine to inosine in endogenous double-stranded RNAs (dsRNAs) to prevent excessive MDA5-driven interferon-stimulated gene expression. The source of endogenous immunogenic dsRNAs remains enigmatic because only a small fraction of ADAR1 substrates activate MDA5, and cellular MDA5 filaments have not been isolated. Here, we couple affinity purification of cellular MDA5 filaments with RNA sequencing to define immunogenic endogenous dsRNAs. Greater than 84% of dsRNAs suppressed by combined DDX3X RNA helicase and ADAR1 base-editing activities were present in MDA5 filaments, compared to less than 1% of dsRNA substrates acted on by ADAR1 alone. Dual substrate dsRNAs consisted of inverted repeats embedded in 3'-UTRs with high base-pair complementarity and longer intervening sequences between repeats, with a minor contribution coming from intermolecular dsRNAs formed by sense and antisense transcripts. Moreover, the majority of dual substrate immunogenic dsRNAs were hyperedited in DDX3X mutant cancers. This reveals the identity of endogenous immunogenic dsRNAs and quality control mechanisms underlying their suppression.

Journal Article↗
PubMed2025

Causal association between 91 circulating inflammatory proteins and primary open-angle glaucoma: a bidirectional Mendelian randomization study.

BACKGROUND: Glaucoma, especially primary open-angle glaucoma (POAG), is a leading cause of irreversible vision loss. While elevated intraocular pressure is a major risk factor, the pathogenesis of POAG also involves genetics, oxidative stress, abnormal hemodynamics, and inflammatory factors. The role of systemic inflammation in POAG remains a subject of debate. This study aimed to investigate the causal relationships between circulating inflammatory proteins and POAG using a bidirectional Mendelian randomization (MR) approach. METHODS: A bidirectional two-sample MR analysis was conducted using genome-wide association study summary statistics. The primary stage involved 91 circulating inflammatory proteins and POAG, followed by a replication stage to verify significant findings using independent data and meta-analysis. The random-effects inverse-variance weighted model was employed as the primary method, complemented by multiple sensitivity analyses employed to ensure robustness, including multivariable MR to adjust for potential confounders. RESULTS: In the primary stage, 9 circulating inflammatory proteins were found to have significant causal effects on POAG. Specifically, the higher levels of Delta and Notch-like epidermal growth factor-related receptor (DNER) (OR: 1.12, 95 % CI: 1.04-1.21, P = 0.004), leukemia inhibitory factor (LIF) (OR: 1.20, 95 % CI: 1.06-1.36, P = 0.003), matrix metalloproteinase-10 (MMP-10) (OR: 1.08, 95 % CI: 1.02-1.16, P = 0.013), and stem cell factor (SCF) (OR: 1.09, 95 % CI: 1.03-1.15, P = 0.005) were positively associated with the risk of POAG. Conversely, the levels of fibroblast growth factor 19 (FGF-19) (OR: 0.88, 95 % CI: 0.82-0.95, P = 0.002), interleukin-18 (IL-18) (OR: 0.92, 95 % CI: 0.86-0.99, P = 0.019), IL-18 receptor 1 (IL-18R1) (OR: 0.96, 95 % CI: 0.92-1.00, P = 0.037), tumor necrosis factor ligand superfamily member 14 (TNFSF14) (OR: 0.91, 95 % CI: 0.86-0.97, P = 0.004), and tumor necrosis factor-related activation-induced cytokine (TRANCE) (OR: 0.94, 95 % CI: 0.88-1.00, P = 0.041) exhibited inverse associations with the risk of POAG. Multivariable MR analysis adjusting for confounders supported the roles of DNER, FGF-19, IL-18, IL18R1, LIF, and SCF. The replication stage confirmed the significant associations for FGF-19 (OR: 0.89, 95 % CI: 0.84-0.95, P = 4.63 × 10-4), IL-18 (OR: 0.93, 95 % CI: 0.89-0.97, P = 0.002), IL-18R1 (OR: 0.96, 95 % CI: 0.93-0.99, P = 0.023), and LIF (OR: 1.18, 95 % CI: 1.04-1.34, P = 0.013). Sensitivity analyses further supported the robustness of these findings. CONCLUSION: This study elucidated the causal relationships between circulating inflammatory proteins and POAG, highlighting FGF-19, IL-18, IL-18R1, and LIF as potential therapeutic targets. These findings provide new insights for the prevention and management of POAG, although further studies are needed to understand the precise biological mechanisms.

Humans↗