Biomedical subjects

Yujie Wang

Publications and source records attributed to Yujie Wang.

8 recordsLinked to original sources

PubMed2026

Aqueous humour extracellular vesicle membrane protein profiling reveals pathological features of refractory macular edema.

BACKGROUND: Both diabetic macular edema (DME) and retinal vein occlusion-related macular edema (RVO-ME) can become refractory to anti-vascular endothelial growth factor (anti-VEGF) therapy, but the underlying mechanisms are unclear. Molecular discrimination of refractory disease could guide personalized treatment. This study examined whether aqueous humor-derived extracellular vesicle (EV) membrane proteins can characterize refractoriness and reveal etiology-specific pathways. METHODS: This prospective cohort study included 28 patients with DME or RVO-ME (14 each), further divided into treatment-naïve and refractory subgroups. Aqueous humour samples were collected before intravitreal anti-VEGF injection. EV membrane proteins were profiled using an EV Array chip targeting 435 antibodies. Differentially expressed proteins were analyzed by bioinformatics, including Gene Ontology, Kyoto encyclopaedia of genes and genomes (KEGG) pathway enrichment, Gene set enrichment analysis (GSEA), and cell-of-origin mapping using public single-cell RNA-seq data. RESULTS: VEGF/VEGFR2 were elevated in treatment-naïve DME and RVO-ME. Refractory DME showed upregulation of C5 and CD34 (complement/immune activation). Refractory RVO-ME exhibited increased CD68 and Annexin A1 with decreased PDGFR (chronic inflammation, vascular dysregulation). RANTES was commonly upregulated in refractory disease. Several EV proteins discriminated refractory cases with high accuracy (AUC 0.898-0.980). Cellular origin suggested immune cell-derived EVs in DME, retinal cell-derived EVs in RVO-ME. External validation confirmed key differences. CONCLUSION: Refractory ME involves distinct pathways: immune-inflammatory activation in DME versus chronic inflammation with vascular dysregulation in RVO-ME. EV membrane proteins from aqueous humor provide insights into therapeutic resistance and hold promise as biomarkers for personalized treatment decisions.

artificial intelligence↗

PubMed2026

Selenium nanoparticle synthesis in Stenotrophomonas maltophilia: Mutagenesis and molecular mechanisms.

Biosynthetic selenium nanoparticles (SeNPs) exhibit superior bioavailability and detoxification potential compared to inorganic selenium forms. In this study, the strain Stenotrophomonas maltophilia SE5, isolated from the feces of piglets (Duroc × Large White × Landrace), was utilized as the wild-type strain and subjected to atmospheric and room temperature plasma (ARTP) mutagenesis. A high-yielding mutant, Mu537, was successfully obtained, which exhibited an enhanced tolerance to sodium selenite, with its maximum tolerable concentration increasing from 1.0 g/L to 1.5 g/L. After 48 h of cultivation, Mu537 achieved an approximate 35% increase in SeNPs conversion rate and a 40% increase in SeNPs concentration relative to the parental strain. Integrated whole-genome sequencing and transcriptomic analysis revealed that pivotal genes associated with efficient SeNPs biosynthesis, including cysB, trxA, and sufE, were significantly up-regulated. These findings provide a systematic understanding of the potential molecular mechanisms driving enhanced SeNPs biosynthesis, offering both high-quality microbial resources and theoretical support for the industrial production of SeNPs.

Stenotrophomonas maltophilia↗

PubMed2026

Ovarian H3K27ac remodeling is associated with impaired follicular development in laying hens with fatty liver hemorrhagic syndrome.

Fatty liver hemorrhagic syndrome (FLHS) is a metabolic disease of laying hens that reduces egg production and is accompanied by reproductive impairment, but the ovarian regulatory mechanisms that connect nutritional stress to follicular dysfunction remain unclear. This study examined whether active chromatin remodeling in the ovary is associated with FLHS induced by a high-energy, low-protein (HELP) diet. Hy-Line Brown hens were assigned to a basal diet or HELP diet, and ovarian tissue was collected for histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing and RNA sequencing. The HELP diet reduced laying performance and the numbers of small yellow and hierarchical follicles, indicating compromised follicular development. Genome-wide H3K27ac profiling identified 2,111 regions with lower acetylation and 1,707 regions with higher acetylation in FLHS ovaries. Genes linked to differential H3K27ac regions were enriched in pathways related to oocyte meiosis, cell cycle control, FoxO signaling, gonadotropin-releasing hormone signaling, and steroid hormone biosynthesis. RNA sequencing identified 341 differentially expressed genes, with a predominance of downregulated genes. Integration of chromatin and transcriptome data highlighted folliculogenesis-related genes, including FGF1, FGF9, and MMP10, that showed reduced H3K27ac enrichment together with decreased expression. Super-enhancer analysis further identified 131 regions with reduced H3K27ac signal in FLHS ovaries, including regions located near PCNA and RAP1A, two genes involved in cellular proliferation and survival signaling. Motif enrichment of differential H3K27ac regions implicated Fos, SF-1/NR5A1, and GATA-4 as candidate transcriptional regulators. These findings indicate that HELP diet-induced FLHS is associated with broad attenuation of active ovarian regulatory elements and reduced expression of genes required for follicle growth, tissue remodeling, and steroidogenic function. The study provides an ovarian epigenomic framework for understanding reproductive decline in FLHS-affected laying hens.

Fatty liver hemorrhagic syndrome↗

PubMed2026

The Znf711-Phf8 complex functions as a transcriptional rheostat essential for neutrophil development.

Neutrophil differentiation is governed by a precise transcriptional and epigenetic program. Here, we identify the zinc finger protein 711 (Znf711) and its partner, the histone demethylase PHD finger protein 8 (Phf8), as essential regulators of terminal granulopoiesis. Contrary to their established role as a transcriptional activator-co-activator pair, we found that the Znf711- Phf8 complex operates through a repressive mechanism. Znf711 promotes neutrophil maturation in a DNA-binding-independent manner by sequestering Phf8. Upon loss of Znf711, Phf8 is recruited by the growth factor independent 1 transcription repressor (Gfi1aa) to the promoter of the master regulator c/ebpα, where SUMOylated Phf8 acts as a corepressor to inhibit its transcription. Furthermore, we delineate a positive feedback loop wherein C/ebpα directly activates znf711 expression, ensuring a high level of c/ebpα at the onset of differentiation. Our findings define the Znf711-Phf8 complex as a critical transcriptional rheostat in neutrophil development.

Humans↗

PubMed2026

Drug-resistant genes, virulence characteristics, and molecular typing of clindamycin-resistant Streptococcus agalactiae in late pregnancy.

BACKGROUND: Streptococcus agalactiae increases the risk of adverse pregnancy outcomes and neonatal infections. Clindamycin is a key alternative for intrapartum prophylaxis in penicillin-allergic women, but the prevalence of clindamycin-resistant S. agalactiae is increasing, posing a significant clinical challenge. METHODS: A total of 178 strains isolated from tertiary hospitals in Jinan and Qingdao, Shandong Province, China, were characterized using antimicrobial susceptibility testing, whole-genome sequencing, multilocus sequence typing, serotyping, and analysis of resistance and virulence genes. RESULTS: All strains were susceptible to penicillin, ampicillin, linezolid, vancomycin, and tigecycline. In contrast, resistance rates to erythromycin, levofloxacin, and tetracycline were 95.5%, 60.1%, and 56.7%, respectively. Six serotypes and 15 sequence types belonging to eight clonal complexes were identified. Notable regional differences were observed. The Ib-ST10-CC12 lineage dominated in Jinan, whereas V-ST529-CC327 was predominant in Qingdao. The resistance gene mreA was ubiquitous (100%), followed by ermB (80.3%). The key virulence genes cylE, hylB, and pavA, were detected in all strains. fbsA (99.4%), the alpha protein family (98.9%), cfb (98.3%), the Pilus Island gene cluster (94.9%), and lmb (92.7%) were also highly prevalent. The two major clindamycin resistance genes, erm and lnuB, exhibited distinctly different enrichment patterns among S. agalactiae clonal complexes, despite a certain overlap in CC19 and CC327. Specifically, erm was significantly enriched in CC12 (serotype Ib), CC19 (III/V), and CC327 (III/V). In contrast, lnuB was predominantly restricted to CC19 and CC327, where it defined a unique phylogenetic subcluster. Significant differences in resistance and virulence gene profiles were observed across different clonal complexes. CONCLUSION: Clindamycin-resistant S. agalactiae in late-pregnancy women in Shandong Province, China exhibits a broad resistance spectrum, diverse molecular types, and significant regional heterogeneity. These findings underscore the need for continued surveillance and region-specific strategies for preventing neonatal S. agalactiae infections.

Humans↗

PubMed2025

Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20 % of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.

Humans↗

PubMed2025

Viral hijacking of host DDX60 promotes Crimean-Congo haemorrhagic fever virus replication via G-quadruplex unwinding.

Crimean-Congo haemorrhagic fever virus (CCHFV) is the most prevalent tick-borne zoonotic bunyavirus, causing severe hemorrhagic fever and fatality in humans. Currently, the absence of approved vaccines or therapeutics for CCHFV infection necessitates the development of innovative therapeutic strategies. Here, we identify a guanine (G)-rich sequence located within the mRNA of the glycoprotein precursor in the medium (M) segment of the CCHFV genome, designated as M-PQS-1664(+). M-PQS-1664(+) can form stable G-quadruplex (G4) structure and functions as a negative regulatory element for viral replication. Host DDX60 is up-regulated in response to CCHFV infection, thereby it is hijacked to unwind M-PQS-1664(+) G4 for facilitating viral replication. The FDA-approved drug Cepharanthine (CEP), which competes with DDX60 to specifically stabilize M-PQS-1664(+) G4 without a global induction of host cellular G4s formation, exhibits remarkable antiviral activity in vitro and in vivo. More importantly, CEP possesses antiviral activity (50% inhibitory concentration ~ 0.2 μM) that having ~ 88 × the potency of ribavirin. Our findings underscore the CCHFV G4s as a promising target for drug development and highlight the significant potential of CEP in combating CCHFV.

Hemorrhagic Fever Virus, Crimean-Congo↗

PubMed2025

Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.

Female↗