Biomedical subjects

Xu Liu

Publications and source records attributed to Xu Liu.

7 recordsLinked to original sources

PubMed2026

Temporal shifts in K-locus composition and expansion of dual-carbapenemase-producing ST11-KL62 Klebsiella pneumoniae: a retrospective genomic surveillance study.

OBJECTIVES: To characterize longitudinal changes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the recent increase in dual-carbapenemase-producing ST11-KL62 isolates. METHODS: We retrospectively analysed 1,239 non-duplicate CRKP isolates recovered at a tertiary hospital in China during 2018-2025. Antimicrobial susceptibility testing, whole-genome sequencing, K-locus and resistance/virulence gene profiling, core-genome single-nucleotide polymorphism analysis, reference-guided plasmid comparison, conjugation and stability assays, and a murine lethality model were used. RESULTS: ST11 accounted for 936/1,239 isolates (75.5%). KL47 declined from 39/151 (25.8%) in 2018-2019 to 45/755 (6.0%) in 2024-2025, whereas KL62 increased from 3/151 (2.0%) to 147/755 (19.5%). Among 148 ST11-KL62 isolates, 13/148 (8.8%) co-harboured blaKPC-2 and blaNDM-1, of which 12/13 (92.3%) met the study's molecular definition of hypervirulent CRKP. Pairwise single-nucleotide polymorphism distances among local ST11-KL62 isolates ranged from 0 to 43 (median, 14), suggesting that clonal expansion may have contributed to their increase. Complete genome analysis of ZD872 located blaKPC-2, blaNDM-1, and major virulence-associated genes on distinct plasmids; related plasmid backbones were predicted in other isolates using short-read comparisons. ZD872 exhibited a hypervirulent phenotype in the murine model. CONCLUSIONS: The ST11 CRKP population underwent temporal shifts in K-locus composition, including expansion of a closely related ST11-KL62 subset carrying dual carbapenemases and hypervirulence-associated markers. These findings support integrating longitudinal genomic surveillance with local transmission analysis.

Carbapenem-resistant Klebsiella pneumoniae↗

PubMed2026

Serum Olink Proteomics Reveals Novel Biomarkers for Early Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor in China, and early diagnosis critically affects the prognosis. Current imaging and pathological biopsy techniques have limitations, including high invasiveness and limited accessibility, while the insufficient sensitivity of serum biomarkers (such as AFP) restricts their use in early screening. In this study, using the Olink proteomics platform based on the proximity extension assay (PEA), we screened for hepatocellular carcinoma-related differentially expressed proteins (DEPs) and constructed a multiprotein diagnostic model. In the discovery cohort, we included 15 patients with newly diagnosed HCCs and 16 healthy controls. DEPs were identified using Olink, and their diagnostic performance was analyzed to identify the candidate biomarkers. In an independent validation cohort, including 116 HCC patients (50 early stage, 66 late stage) and 83 healthy controls, we further validated the expression levels and diagnostic performance of identified proteins─C1QA and GFER. The C1QA and GFER expression levels were significantly higher in the serum of patients with early and late HCC stages compared to healthy controls. By constructing a multiprotein diagnostic model, we identified C1QA, GFER, and AFP as the optimal diagnostic combination, demonstrating a combined diagnostic AUC of 0.92 and 0.99 for early-stage and advanced-stage HCC, respectively.

Humans↗

PubMed2026

Causal relationship between asthma and hernia risk: A Mendelian randomization study.

Epidemiological associations between asthma and various hernia subtypes have been reported, but the causality and direction remain unclear. This study employs a two‑sample Mendelian randomization (MR) approach to systematically assess the causal associations between asthma and 6 hernia subtypes. Using publicly available summary data of genome-wide association studies, asthma was selected as the exposure, and diaphragmatic hernia, umbilical hernia, femoral hernia, hiatus hernia, inguinal hernia, and ventral hernia were selected as outcomes. Instrumental variables were strictly screened (F-statistic > 10). The inverse‑variance weighted method was used as the primary analytical approach, supplemented with MR Egger and weighted median methods. Sensitivity analyses included heterogeneity tests, horizontal pleiotropy tests, Steiger directionality tests, leave‑one‑out analyses, and Radial MR. Reverse MR was performed for validation. Forward MR analyses revealed a significant positive causal effect of asthma on diaphragmatic hernia (odds ratio [OR] = 1.19, 95% confidence interval [CI]: 1.08-1.31, P < .001) and a suggestive association with umbilical hernia (OR = 1.19, 95% CI: 1.05-1.34, P = .007). The umbilical hernia association was significant only by the inverse‑variance weighted method; weighted median (P = .102) and MR-Egger (P = .210) estimates were not statistically significant, and the estimate attenuated after outlier removal (confirmatory OR = 1.13, 95% CI: 1.01-1.26, P = .028). Sensitivity analyses showed no significant heterogeneity or pleiotropy. Reverse MR did not identify significant causal effects of hernias on asthma, although power limitations for certain hernia subtypes should be considered. No significant associations were observed between asthma and the other hernia subtypes, although the null findings for femoral and ventral hernias should be interpreted with caution due to limited statistical power. This study provides genetic evidence supporting asthma as a causal risk factor for diaphragmatic hernia, with a suggestive association for umbilical hernia. The diaphragmatic hernia finding was robust across multiple sensitivity analyses, whereas the umbilical hernia association was less consistent and requires further confirmation. These findings contribute to a deeper understanding of the mechanistic links between asthma and specific hernia subtypes.

Mendelian Randomization Analysis↗

PubMed2026

Distinct spatial immune microenvironment features of different EGFR mutation subtypes in early-stage lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinoma (LUAD), yet their influence on the spatial tumor immune microenvironment (TIME) in early-stage disease remains unclear. We characterized the spatial TIME in 144 treatment-naïve, early-stage LUADs using integrated genomic sequencing and multiplex immunohistochemistry (mIHC). Although EGFR-mutant tumors overall displayed reduced CD8 + T-cell infiltration compared with EGFR-wild-type tumors, substantial heterogeneity was observed among EGFR subtypes. Specifically, L858R and rare-variant subtypes exhibited higher tumor mutational burden, greater CD8 + T-cell density, and enrichment of T-cell-dominant cellular neighborhoods relative to 19del subtype, consistent with a comparatively immune-infiltrated phenotype. In contrast, 19del tumors showed lower T-cell infiltration. TP53 co-mutation was also associated with enhanced CD8 + T-cell infiltration. These cross-sectional findings identify hypothesis-generating spatial immune phenotypes across EGFR-mutant LUAD subtypes; their potential relevance to perioperative treatment selection requires prospective validation in outcome-annotated treatment cohorts.

Humans↗

PubMed2025

O-GlcNAcylation of nuclear proteins in the mouse liver exhibit daily oscillations that are influenced by meal timing.

The liver circadian clock and hepatic transcriptome are highly responsive to metabolic signals generated from feeding-fasting rhythm. Previous studies have identified a number of nutrient-sensitive signaling pathways that could interpret metabolic input to regulate rhythmic hepatic biology. Here, we investigated the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) in mediating metabolic regulation of rhythmic biology in the liver. We observe daily oscillation of global nuclear protein O-GlcNAcylation in the liver of mice subjected to night-restricted feeding (NRF) using label-free global O-GlcNAc proteomics. Additional site-specific O-GlcNAc analysis by tandem mass tag mass spectrometry further supports temporal differences in O-GlcNAcylation by revealing day-night differences. Proteins involved in gene expression are enriched among rhythmically O-GlcNAcylated proteins, suggesting rhythmic O-GlcNAcylation may directly regulate the hepatic transcriptome. We show that rhythmic O-GlcNAcylation can also indirectly modulate nuclear proteins by interacting with phosphorylation. Several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. Specifically, we show that O-GlcNAcylation occurs at a phospho-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), thus regulating its stability and transcriptional output. Finally, we report that day-restricted feeding (DRF) in the nocturnal mouse significantly alters O-GlcNAcylation pattern. Whereas global O-GlcNAcylation analysis indicates dampening of global O-GlcNAcylation rhythm in mice fed under DRF, site-specific analysis reveals differential responses of O-GlcNAc sites when timing of food intake is altered. Notably, a substantial number of O-GlcNAcylation sites exhibit inverted day-night profiles when mice are subjected to DRF. This suggests the dysregulation of daily nuclear protein O-GlcNAcylation rhythm may contribute to the disruption in liver transcriptome previously observed in DRF condition. In summary, our results provide new mechanistic insights into metabolic regulation of hepatic transcriptional regulators via interplay between O-GlcNAcylation and phosphorylation and shed light on the deleterious effects of improper mealtimes.

Animals↗

PubMed2024

Metagenomic analysis demonstrates distinct changes in the gut microbiome of Kawasaki diseases children.

BACKGROUND: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. METHODS: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. RESULTS: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions. CONCLUSION: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD.

Humans↗

PubMed2020

Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses.

OBJECTIVE: Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS: Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS: As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION: Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

Bayes Theorem↗