Biomedical subjects

Xiaoyu Zhang

Publications and source records attributed to Xiaoyu Zhang.

3 recordsLinked to original sources

PubMed2026

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96 h) and chronic (8 weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals↗

PubMed2026

Oncogenic SF3B1 mutations alter the splicing of mRNA noncoding regions to induce a novel therapeutic vulnerability.

Oncogenic mutations of SF3B1 are common in myeloid cancers, chronic lymphocytic leukemia (CLL), and select solid tumors. Their mechanistic basis for promoting oncogenesis has been investigated in detail, with the stereotyped missplicing of messenger RNA (mRNA) protein coding sequences most intensively studied. These changes, in genes such as MAP3K7, BRD9, and ABCB7, typically lead to loss of function, thus contributing to cancer pathogenesis. Here, we systematically analyzed the impact of mutant SF3B1 on noncoding regions of mRNA transcripts across disease types, in both cell lines and primary patient specimens. This identified numerous novel and highly reproducible splicing alterations in such regions. Studies of a target gene, DCAF16, revealed multiple complex mutation-induced alterations in its 5' and 3' untranslated regions (UTRs). Remarkably, these were mechanistically associated with increased DCAF16 protein levels in SF3B1-mutant cells, representing, to our knowledge, the first time that oncogenic SF3B1 has been found to increase levels of a target protein in a gain-of-function manner. DCAF16 is a substrate recognition adapter for the DDB1/CUL4 E3 ubiquitin ligase complex. Novel protein degrader small molecules that coopt DCAF16 to degrade BRD4 as a neosubstrate demonstrated preferential selectivity for SF3B1-mutant cancers and CLL primary patient specimens due to increased DCAF16 protein levels. In turn, this reveals the therapeutic relevance of mutant SF3B1 dysregulation of transcript UTRs and uncovers a novel strategy for the treatment of these important neoplasms.

Humans↗

PubMed2025

Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank.

BACKGROUND: Genetic factors may have a significant influence on the likelihood of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD). The present study was conducted to explore how single-nucleotide polymorphism (SNP) impacts the development of fibrosis in those suffering from NAFLD. MATERIALS AND METHODS: Utilizing the UK Biobank dataset, we conducted a nested case-control analysis among NAFLD participants, defining the case group as those with liver fibrosis and cirrhosis during follow-up. For our in vitro investigations, we employed the LX-2 human hepatic stellate cell line. Our procedures included cultivating these cells, employing SAMM50-rs2073080 plasmid techniques to enhance the expression of recently discovered SNPs, and conducting biochemical assays. To quantify gene expression, we used real-time PCR with fluorescence detection. RESULTS: The study analyzed data from 5467 participants (1094 cases and 4373 controls). Genome-wide association analysis identified nine significant loci, including the novel rs2073080 variant, strongly associated with NAFLD-associated hepatic fibrosis. In vitro TGF-β modeling revealed significant upregulation of α-SMA and COL1A1, confirming model effectiveness. Oxidative stress markers like elevated malondialdehyde (MDA) and reduced catalase (CAT) and superoxide dismutase (SOD) levels indicated liver damage in the TGF-β group. SAMM50-rs2073080 was upregulated in the NAFLD-associated fibrosis model. In vitro experiments on LX-2 cells showed that SAMM50-rs2073080 overexpression led to increased fibrosis, as indicated by higher cellular MDA levels and lower CAT and SOD levels, compared to the vector group. CONCLUSION: Our research highlights a significant association of SAMM50-rs2073080 with the progression of NAFLD to hepatic fibrosis, and the in vitro experiments further corroborated these findings.

Humans↗