Biomedical subjects

Yanan Zhang

Publications and source records attributed to Yanan Zhang.

5 recordsLinked to original sources

PubMed2026

A rare germline TXNIP missense mutation may contribute to the genesis of familial ovarian mature teratoma in human.

Ovarian mature teratoma (OT) is a common ovarian germ cell tumor, and its early onset, multifocality, recurrence and familial aggregation suggest that genetic susceptibility contributes to a subset of cases. Whole-exome sequencing was used to identify candidate susceptibility variants in a family with recurrent and multifocal OT. A rare heterozygous germline TXNIP variant, NM_006472.6:c.1049C > T (p.Pro350Leu), was identified and confirmed by Sanger sequencing. p.Pro350Leu TXNIP showed lower steady-state abundance, faster cycloheximide-chase decay, and greater K48-linked polyubiquitination than wild-type TXNIP. Familial OT specimens also showed weaker TXNIP staining and stronger GLUT1 staining than sporadic OT specimens. TXNIP depletion increased plasma-membrane GLUT1, glucose uptake, lactate production and hyperactivated the PI3K/mTOR pathway, and familial tissues reproduced this PI3K/mTOR-dominant state. To our knowledge, this is the first genomic and functional investigation of a germline susceptibility mechanism for human familial ovarian mature teratoma. These findings establish TXNIP as the first functional candidate susceptibility gene for this phenotype and connect inherited susceptibility to ubiquitin-dependent protein turnover, GLUT1-driven metabolic reprogramming, and PI3K/mTOR-dominant follicular signaling.

Missense mutation↗

PubMed2026

The transcription factor PavERF28 promotes fruit softening by regulating cell wall degradation in sweet cherry (Prunus avium L.).

Fruit softening is a critical determinant of shelf life and marketability in sweet cherry (Prunus avium L.). This process is predominantly driven by cell wall disassembly, which is tightly regulated by transcription factors. Despite evidence for ethylene's role in sweet cherry softening, how these signals are transduced to regulate the expression of cell wall-modifying genes is unclear. Here, we identified the ethylene-responsive transcription factor PavERF28 as a key regulator in this process. Overexpression of PavERF28 significantly upregulated the transcriptional levels of genes involved in pectin degradation (including genes encoding polygalacturonase, pectin methylesterase inhibitor, and pectate lyase), thus effectively enhancing fruit softening. Moreover, heterologous overexpression of PavERF28 in tomato confirmed its function in promoting fruit softening. At the molecular level, PavERF28 was shown to directly activate the expression of two polygalacturonase genes (PavPG1 and PavPL5) by binding to their promoters, which catalyze pectin depolymerization and thus drive softening. Collectively, our work provides an in-depth elucidation of the regulatory mechanism by which ERF family members control fruit softening in sweet cherry and offers potential targets for the manipulation of fruit ripening, especially softening.

Cell Wall↗

PubMed2026

Yorkie/Scalloped-OVOL-Rac1 axis controls insect wing development by promoting cell proliferation.

The regulation of organ size is a fundamental question in developmental biology, and insect wings provide a powerful model for elucidating the genetic mechanisms underlying morphogenesis. Although the conserved Hippo signaling pathway plays a central role in controlling tissue growth, its precise regulatory network during wing development remains incompletely understood. Here, we identify the zinc finger transcription factor OVOL as a critical mediator of Hippo signaling in insect wing development. We indicate that OVOL is essential for normal wing formation in both Locusta migratoria and Drosophila melanogaster, regulating cell proliferation and trichome patterning. Through transcriptomic analysis and functional validation, we further identify the small GTPase Rac1 as a key downstream effector of OVOL that promotes proliferative growth. Moreover, we find that OVOL expression is directly activated by the Yorkie/Scalloped (Yki/Sd) complex, the core transcriptional effector of the Hippo pathway, without forming a feedback loop. This regulation is mediated through a specific Sd-binding motif (GATAA) within the OVOL promoter. Importantly, Yki/Sd-induced Rac1 expression is dependent on OVOL. Collectively, our findings establish the Yorkie/Sd-OVOL-Rac1 pathway that governs insect wing development by promoting cell proliferation, providing mechanistic insights into organ size regulation in animals.

Cell proliferation↗

PubMed2026

Glycolysis-dependent reactive oxygen species mediate desmopressin acetate-induced rescue of platelet dysfunction caused by antiplatelet therapy.

Antiplatelet therapy is extensively used in the prevention and treatment of cardiovascular and cerebrovascular diseases; however, life-threatening hemorrhage requires urgent reversal of platelet dysfunction. Desmopressin acetate has been proposed as a rescue strategy, yet its efficacy and underlying mechanisms remain incompletely understood, particularly regarding redox regulation. A mouse carotid artery blood flow injury model was employed to evaluate the effects of desmopressin acetate on platelet and coagulation dysfunction induced by antiplatelet therapy. Proteomic analyses were performed in both patients and mice to identify differentially expressed proteins. Genetic knockout and pharmacological inhibition approaches were used to investigate the mechanistic pathways involved. Desmopressin acetate effectively restored platelet function and coagulation capacity in antiplatelet-treated mice. Proteomic profiling identified peroxiredoxin-5, a key antioxidant enzyme, as significantly upregulated following antiplatelet therapy but markedly downregulated after desmopressin acetate administration; these findings were validated in plasma samples from 10 patients who received dual antiplatelet therapy for unruptured intracranial aneurysms. Functional studies demonstrated that proteomic profiling identified peroxiredoxin-5 supplementation impaired platelet function, whereas proteomic profiling identified peroxiredoxin-5 knockout or inhibition significantly improved platelet activity. Notably, desmopressin acetate primarily suppressed liver-derived proteomic profiling identified peroxiredoxin-5 expression. Mechanistically, desmopressin acetate enhanced platelet glycolysis via phosphofructokinase-2/fructose-2,6-bisphosphatase 3 activation, leading to increased intracellular reactive oxygen species levels. Inhibition of phosphofructokinase-2/fructose-2,6-bisphosphatase 3 attenuated glycolysis, reduced reactive oxygen species generation, and restored proteomic profiling identified peroxiredoxin-5 expression, thereby abolishing the platelet-rescuing effects of desmopressin acetate. Desmopressin acetate rescued platelet dysfunction induced by antiplatelet therapy through a glycolysis-reactive oxygen species-proteomic profiling identified peroxiredoxin-5 axis, in which glycolysis-driven reactive oxygen species generation plays a central regulatory role. These findings indicate redox modulation as a critical mechanism underlying desmopressin acetate-mediated platelet rescue and suggest a potential therapeutic strategy for managing severe bleeding associated with antiplatelet therapy.

Animals↗

PubMed2025

Mendel randomization confirmed gastroesophageal reflux disease may increase the risk of mental disorders.

BACKGROUND: The potential causal relationship between gastroesophageal reflux disease (GERD) and mental disorder was analyzed using the mendelian randomization (MR) method. METHODS: Data are derived from genome-wide association study (GWAS) summary data, using gastroesophageal reflux disease (GERD) as the exposure factor. Single nucleotide polymorphisms (SNPs) significantly associated with GERD were selected as instrumental variables (IVs), and mental disorders (bipolar disorder, major depression, Alzheimer's disease, anorexia nervosa, anxiety, and obsessive-compulsive disorder) were used as outcome variables. The inverse variance weighted (IVW) method is used as the main analysis method, and MR-Egger regression, weighted median (WM) method, simple mode and weighted mode are used as supplementary methods for Mendelian randomization (MR) analysis. Cochran's Q test and P value are used to quantify heterogeneity, MR-Egger regression was used to evaluate the multilevel effect test of SNPs, and leave-one-out method to determine whether there are potential SNPs, and to evaluate the stability of the results. Odds ratio (OR) and 95% confidence interval (CI) were used as effect indicators to evaluate whether there is a causal relationship between GERD and mental disorders. RESULTS: IVW demonstrated a causal relationship between GERD and bipolar disorder (OR = 1.70, 95%CI = 1.39-2.09, P < 0.05) and anorexia nervosa (OR = 0.71, 95%CI = 0.52-0.99, P < 0.05). Furthermore, there is a weak causal relationship between GERD and major depression (OR = 1.01, 95%CI = 1.01-1.02, P < 0.05) and anxiety (OR = 1.01, 95%CI = 1.01-1.01, P < 0.05). Similarly, there is no evidence of a causal relationship between GERD and Alzheimer's disease (OR = 0.95, 95%CI = 0.87-1.03, P > 0.05) or obsessive-compulsive disorder (OR = 0.95, 95%CI = 0.67-1.36, P > 0.05). Cochran's Q test for heterogeneity shows that there is no significant heterogeneity (P > 0.05) for bipolar disorder, anxiety, and obsessive-compulsive disorder. However, major depression, Alzheimer's disease, and anorexia nervosa have some degree of heterogeneity (P < 0.05). Horizontal pleiotropic analysis showed that the P values for six mental disorders (0.750, 0.296, 0.154, 0.798, 0.893, 0.451) were all greater than 0.05. Leave-one-out analysis and funnel plot showed that MR analysis results can be considered relatively stable. All F are > 10, indicating no weak IVs bias. CONCLUSION: GERD can obviously increase the risk of bipolar disorder; the increased risk of anxiety disorder is very slight. There is no clear evidence to support the causal relationship between GERD and four other mental disorders, including major depression, Alzheimer's disease, anorexia nervosa, and obsessive-compulsive disorder.

Humans↗