Biomedical subjects

Qian Wang

Publications and source records attributed to Qian Wang.

8 recordsLinked to original sources

PubMed2026

TET2 promotes monocyte inflammatory activation in asthma via ALKBH5-m6A regulation and PI3K signaling: evidence from m6A-SNP and single-cell analyses.

Asthma is a complex inflammatory airway disease with strong genetic determinants, yet the functional relevance of most asthma-associated non-coding variants remains unclear. Emerging evidence suggests that N6-methyladenosine (m6A) modification may serve as a critical epitranscriptomic link between genetic variation and immune regulation. In this study, we aimed to systematically identify functionally relevant m6A-regulated genes in asthma by integrating large-scale GWAS data, m6A-SNP annotations, and single-cell transcriptomic analyses, and to investigate their roles in monocyte-driven airway inflammation. We identified TET2 as a key m6A-regulated gene associated with both asthma and lung function, which was selectively upregulated in monocytes during asthma and accompanied by activation of inflammatory and PI3K signaling pathways. Mechanistic experiments further demonstrated that inflammatory stimulation induced ALKBH5 expression, reduced m6A modification of TET2 mRNA, and increased TET2 protein levels, thereby promoting PI3K/AKT signaling and pro-inflammatory cytokine production, whereas inhibition of TET2 or ALKBH5 attenuated these effects. Collectively, these findings demonstrate that ALKBH5-mediated m6A regulation of TET2 enhances PI3K/AKT signaling in monocytes, thereby promoting inflammatory responses in asthma. Our study establishes TET2 as a key m6A-regulated gene linking genetic susceptibility to monocyte-driven inflammation, and highlights the ALKBH5-m6A-TET2 axis as a potential therapeutic target for modulating aberrant immune responses in asthma.

Humans↗

PubMed2026

Joint Effects of Long-Term Obesity and Genetic Susceptibility on Sex-Specific Brain Aging.

OBJECTIVE: This study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging. METHODS: We analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females). Sex-specific XGBoost models estimated multimodal brain age. We derived 16-year longitudinal obesity trajectories from repeatedly collected anthropometric measurements. Polygenic risk scores were constructed based on 55 independent genetic loci. Multivariable logistic regression examined associations of obesity trajectories and genetic risk with brain age acceleration. RESULTS: A total of 8198 (49.73%) males and 9089 (48.84%) females had accelerated brain aging. High genetic risk significantly increased brain age acceleration odds (males: OR = 1.39; females: OR = 1.34). Crucially, the high-stable obesity trajectory exerted a stronger effect in males (OR = 1.90, 95% CI: 1.64-2.21) than in females (OR = 1.25, 95% CI: 1.12-1.40), with the joint presence of high genetic risk and high-stable obesity amplifying risk to an OR of 2.78 in males and 1.57 in females. Conversely, shifting from obesity to non-obesity reduced risk by 30% in males and 18% in females. CONCLUSIONS: These findings underscore long-term obesity as a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.

brain aging↗

PubMed2026

Rapid transcriptional reprogramming underlies Fusarium wilt resistance in strawberry: insights from comparative physiological and transcriptomic analyses.

INTRODUCTION: Fusarium wilt caused by Fusarium oxysporum f. sp. fragariae (Fof) severely constrains strawberry production, yet the underlying resistance mechanisms remain unclear. METHODS: A total of 64 strawberry germplasm accessions were evaluated for Fusarium wilt resistance. Integrated physiological and transcriptomic analyses were subsequently performed using the highly resistant cultivar 'Akihime' (ZJ) and the highly susceptible cultivar 'Ning Yu' (NY). RESULTS: Resistant resources were abundant, particularly among wild strawberry accessions. Compared with NY, ZJ exhibited higher soluble sugar accumulation, reduced oxidative damage, and increased peroxidase (POD) and phenylalanine ammonia-lyase (PAL) activities. Transcriptomic analyses revealed distinct temporal response patterns: ZJ underwent rapid and extensive transcriptional reprogramming at 24 h post-inoculation, whereas NY showed limited early responses but pronounced changes at 120 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that the early response of ZJ was mainly associated with stress-related processes, jasmonic acid-mediated signaling, transmembrane transport, plant-pathogen interaction, mitogen-activated protein kinase (MAPK) signaling, glutathione metabolism, plant hormone signal transduction, and secondary metabolism. Quantitative real-time polymerase chain reaction (qRT-PCR) validation supported the RNA-seq results and identified candidate genes associated with pathogen recognition, signaling, redox regulation, and protein homeostasis. DISCUSSION: These results indicate that rapid early immune activation and coordinated physiological and metabolic reprogramming are closely associated with strawberry resistance to Fof and provide useful germplasm and candidate genes for future functional validation and resistance breeding.

Fusarium oxysporum f. sp. fragariae↗

PubMed2026

Repeated Cross-Sectional Surveillance and ORF5-Based Molecular Epidemiology of Porcine Reproductive and Respiratory Syndrome Virus in Anhui Province, China, 2019-2024.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major threat to swine production, and its circulation after the African swine fever outbreak requires continued surveillance. This study investigated the temporal, regional, and genetic characteristics of PRRSV in Anhui Province from September 2019 to November 2024. Ten rounds of repeated cross-sectional surveillance were conducted at 147 slaughterhouses and 21 rendering plants. Tissue samples were collected by random, cluster, or risk-based sampling, pooled in groups of five, and tested by RT-qPCR. Representative positive samples with Ct values < 25 underwent ORF5 amplification, Sanger sequencing, and phylogenetic analysis. A total of 994 site visits yielded 18,733 tissue samples. No positive samples were detected in autumn 2020 or spring 2021, whereas PRRSV was detected again from autumn 2021 and subsequently fluctuated. The highest site-level positivity was 41.18% in autumn 2023, and the highest estimated individual-level positivity was 4.66% in spring 2023. Regional differences were statistically significant, with the highest site-level positivity in northern Anhui, and pooled-sample positivity was higher in rendering plants than in slaughterhouses. All 24 ORF5 sequences belonged to PRRSV-2 and mainly clustered with NADC30-like, NADC34-like, or MLV/classical strains. These findings demonstrate temporal fluctuations and lineage coexistence, supporting continued multisource surveillance and broader genomic and antigenic evaluation.

NADC30-like↗

PubMed2026

Intramuscular patient-derived xenografts achieve high engraftment rates in gastric cancer: implications for pharmacodynamic testing and genomic biomarker discovery.

BACKGROUND: Gastric cancer (GC) exhibits marked inter-patient heterogeneity, limiting empirical chemotherapy efficacy. Patient-derived xenograft (PDX) models preserve the molecular features of parental tumors and can serve as pharmacodynamic surrogates, but conventional subcutaneous PDX suffers from low engraftment rates. This study evaluated an optimized intramuscular PDX platform for individualized drug testing in GC and applied whole exome sequencing (WES) for biomarker identification (Clinical trial registry: ChiCTR-OOC-17012731). MATERIALS AND METHODS: Ninety-eight treatment-naive GC patients were enrolled between April 2018 and December 2020. Fresh tumor tissues were engrafted into NCG mice by intramuscular transplantation. Drug efficacy was evaluated using tumor cell necrosis rate and Ki-67 expression. WES was performed on 32 engrafted tumorgrafts to characterize driver mutations in fast- and slow-growing subgroups. RESULTS: An engraftment rate of 71.7% (43/60) was achieved, substantially exceeding rates reported in prior studies. Clinical characteristics were independent of engraftment success and outgrowth time (all p > 0.05). Fast- and slow-growing tumorgrafts diverged in frequently altered genes: KMT2C, APOB, CDK12 and MSH2 predominated in fast-growing grafts, whereas TP53, CHD3 and TET2 were enriched in slow-growing grafts. Slow-growing tumorgrafts correlated with longer progression-free survival (p = 0.02). PDX-guided treatment was associated with improved prognosis. CONCLUSIONS: Intramuscular transplantation into NCG mice yields high engraftment rates for GC PDX. PDX-guided chemotherapy selection is associated with favorable outcomes. Driver mutation divergence between fast- and slow-growing tumorgrafts provides candidate prognostic biomarkers.

Animals↗

PubMed2026

The psychosocial supports and interventions accessed by family members of patients with developmental and epileptic encephalopathies: A systematic review.

AIM: Family members of patients with developmental and epileptic encephalopathies (DEEs) face profound emotional, social and practical challenges, yet little is known about how they access psychosocial support. We synthesised the literature on the psychosocial support accessed by family members of patients with DEEs, including evidence-based interventions. METHOD: Four databases were searched. Two reviewers independently screened and extracted data, appraised study quality (QualSyst Tool), and determined certainty of evidence (GRADE-CERQual Framework). Data were synthesised using inductive thematic analysis. RESULTS: 28 papers comprising 27 unique studies were included and methodological quality was high overall (median = 0.91, IQR = 0.85-1.00). Most studies focused on parent experiences; only two included siblings' perspectives. Families reported high psychological needs which were rarely met by psychological support. Clinicians rarely provided adequate information, quality communication or addressed mental health. Families valued respite care, but experienced barriers to access. Peer support was the most common and valued resource. Three studies tested interventions and appeared feasible and acceptable for parents. However, evidence for intervention effectiveness is preliminary and limited to small, uncontrolled pilot studies. INTERPRETATION: Gaps exist in psychosocial support provision for families of patients with DEEs, including insufficient research on siblings' and grandparents' needs, and lack of evidence-based interventions. We propose evidence-informed research and implementation strategies to address these gaps.

Humans↗

PubMed2026

Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) and type 2 diabetes (T2D) have a more severe cardiac phenotype and worse clinical course than non‑diabetic patients. To identify how T2D aggravates the disease and whether the most abundant cardiac protein, myosin, is involved, we combined functional, structural and mass spectrometry analyses of human samples. METHODS: Left ventricular septal myectomy samples from genotype‑negative (G-) HCM patients without T2D (G- , N = 19) and with T2D (G-T2D, N = 15) were analyzed mainly using fluorescent ATP chase experiments, small‑angle X‑ray diffraction and targeted myosin heavy chain proteomics. RESULTS: Mant‑ATP chase measurements showed a lower fraction of myosin heads in the energy‑conserving super‑relaxed (SRX) state in G-T2D compared to non-diabetic myocardium. In parallel, X‑ray diffraction showed trends toward structural alterations in myosin organization in G-T2D tissue, consistent with altered OFF/ON state equilibrium. Targeted mass spectrometry identified hyperacetylation of several myosin lysine residues in G-T2D, including K847 within the S2 region. All‑atom molecular dynamics simulations indicated that K847 acetylation disrupts stabilizing electrostatic interactions in the interacting‑heads motif, which is associated with the OFF state. CONCLUSIONS: Disruption of myosin super‑relaxation emerges as a central cellular defect in G-T2D HCM myocardium and can be mechanistically linked to site‑specific myosin hyperacetylation at K847, providing a potential therapeutic target for genotype‑negative HCM with T2D.

Humans↗

PubMed2026

The evolution of Ca2+-ATPases across plants with profiles in Rhododendron and the function of key members in alleviating high calcium stress.

Ca2+-ATPase (CAP) is a key Ca2+ efflux protein in plants. Our previous research suggests that CAPs may play a crucial role in the adaptation of rhododendrons to high calcium environments. However, the evolution, variation, characteristic expression, and subfunctionalization of this gene family in Rhododendron remain unknown. Through the analysis of pan-genomes and pan-transcriptomes, we elucidated the systematic evolution of CAPs in plants, as well as their characteristic expression patterns in Rhododendron. During the evolutionary process from lower to higher plants, CAPs can be divided into six clades and exhibit structural conservation. CAPs have emerged and differentiated in lower plants such as algae, and they have undergone significant amplification in Eudicots plants like rhododendrons. Three Rhododendron species (Rhododendron bailiense, R. delavayi, and R. irroratum) located in the karst province of Guizhou in Southwest China exhibit the highest copies of CAPs, suggesting a strong association between CAP copy number variation and habitat, particularly in high calcium environments. Through multiple transcriptome analyses, we revealed that CAPs are induced under various environmental/developmental conditions (e.g. karst environments, high altitude, early flower development, hormones, etc.). Co-expression network analysis highlighted key members of calcineurin B-like protein (CBL) and CBL-interacting protein kinases (CIPK) that are associated with the high expression of CAPs. Experimental validation demonstrated that CAPb1 and CAPd1 significantly alleviate high calcium stress, and the CAPb1-CIPK1-CBL1 and CAPd1-CIPK2-CBL1 modules can further enhance the alleviation. These findings provide new insights into the evolution, characteristic expression, and function of CAPs, as well as new perspectives on the high calcium adaptability of rhododendrons.

Journal Article↗