Biomedical subjects

Xinyue Zhang

Publications and source records attributed to Xinyue Zhang.

7 recordsLinked to original sources

PubMed2026

Gut microbiota-driven indole-3-propionic acid and kynurenine production is associated with improved metabolic adaptation in periparturient dairy cows.

BACKGROUND: Gastrointestinal microbes convert tryptophan into various bioactive metabolites that influence host energy metabolism; however, these mechanisms are not well understood in periparturient dairy cows, which experience marked metabolic challenges during this period. RESULTS: In this study, we used periparturient dairy cows with rumen and ileal cannulas as in vivo models. Blood, rumen fluid, ileal digesta, and fecal samples were collected at four time points during the periparturient period. By combining metagenome-assembled genomes (MAGs) and targeted metabolite quantification, we characterized microbial tryptophan metabolism and associated metabolite profiles during the periparturient period. The results showed that postpartum cows exhibited significantly increased serum concentrations of triglyceride (TG), aspartate aminotransferase (AST), β-hydroxybutyrate (BHBA), and total bilirubin (T-Bil) compared with prepartum cows, together with decreased levels of several tryptophan metabolites, including indole-3-propionic acid (IPA) and kynurenine (KYN), indicating that tryptophan deficiency might aggravate metabolic disturbances. Metagenomic analysis identified 578 high-quality MAGs, of which 461 contained genes involved in microbial tryptophan metabolic pathways. Among these, the ruminal taxon CAG-791 harbors acdA and contributes to IPA production, whereas the hindgut taxon Treponema_D harbors kynB and promotes KYN formation. Decreases in both taxa were consistent with the reduced levels of these metabolites observed above. In a follow-up in vivo trial with tryptophan supplementation, the abundance of CAG-791 and Treponema_D increased, along with tryptophan-derived metabolites (IPA and KYN), which further partially mitigated metabolic disturbances. CONCLUSIONS: These findings characterize spatial and temporal changes in tryptophan metabolites and gut microbial features in periparturient dairy cows, and provide integrated evidence that alterations in tryptophan metabolism are associated with postpartum metabolic adaptation, thereby supporting the potential of tryptophan-targeted nutritional strategies to improve metabolic health in dairy cows.

Gastrointestinal microbiome↗

PubMed2026

Genome-wide epigenomic atlas and multi-omics responses of Eriocheir sinensis to natural extreme heat.

BACKGROUND: Global climate warming has led to increasingly frequent and prolonged extreme summer heat events, posing severe environmental challenges to aquaculture systems. Extreme summer heat can disrupt the performance of pond-cultured ectotherms. The Chinese mitten crab (Eriocheir sinensis) is an economically important freshwater crustacean, but coordinated molecular differences following contrasting natural summers remain incompletely characterized. RESULTS: We performed a comprehensive multi-omics analysis integrating meteorological monitoring, mRNA/lncRNA transcriptomics, small-RNA profiling of miRNAs, DNA methylomics, and LC-MS metabolomics in E. sinensis populations collected from Yancheng, China, between 2020 and 2024. Across the ten farms, survival was significantly lower in 2024, whereas yield and the proportion of large individuals showed nonsignificant downward trends. Gene-set analyses showed negative enrichment of cellular heat-response, protein-folding, oxidative-phosphorylation, and mitochondrial ATP-production terms in the 2024 cohort at the time of sampling. The integrated transcript annotation contained 72,240 lncRNAs and 63,833 mRNAs, and CpG was the predominant methylation context. Differential methylation analysis identified 73 regions and 185 cytosines, with hypomethylated events predominating within the significant subset. Metabolomic profiles differed between annual cohorts and mapped to carbohydrate, lipid, and amino-acid pathways. Cross-omics integration prioritized eight candidate genes-ADCY9, UNC79, UBN1, IFT52, ACO2, LOC126986070, LOC127001126, and LOC126997895-and qPCR reproduced the reported directions of expression for selected RNAs. CONCLUSION: This study provides the first integrative multi-omics framework for understanding chronic heat adaptation in E. sinensis. By linking transcriptomic, epigenomic, and metabolic remodeling, we elucidate the molecular mechanisms underlying energy imbalance, epigenetic reprogramming, and immune dysregulation during prolonged thermal stress. These findings offer valuable insights and genomic resources for breeding heat-tolerant crab strains and improving aquaculture resilience under ongoing climate change.

DNA methylation↗

PubMed2026

MET-Aberrant non-small cell lung cancer: from kinase dependence to cell-surface targetability-mechanistic basis and biomarker framework for bispecific antibodies and antibody-drug conjugates.

MET-aberrant non-small cell lung cancer (NSCLC) is not a uniform therapeutic entity. Its biology, diagnostic pathways, and treatment sensitivity differ across MET exon 14 skipping alteration (METex14), MET amplification, and MET overexpression. This heterogeneity cannot be fully explained by conventional event-based classification and is reflected in the distinct clinical activity of MET tyrosine kinase inhibitors (MET-TKIs), bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). With the emergence of antibody-based therapies, MET has evolved from a signaling driver to a cell-surface target for receptor modulation and payload delivery. We therefore propose a clinically anchored two-dimensional framework for interpreting therapeutic relevance in MET-aberrant NSCLC: kinase dependence and cell-surface targetability. Neither dimension should be regarded as a directly measurable binary variable. Kinase dependence is inferred from genomic and treatment-contextual proxies, most strongly METex14 and, more conditionally, high-level focal MET amplification. Cell-surface targetability is approximated by drug-specific IHC assessment of assay-defined c-MET protein expression; however, receptor internalization, intracellular trafficking, and payload delivery capacity remain incompletely measurable in routine clinical practice. Within this framework, MET-TKIs have the most evidence-supported established role in tumors with evidence of MET-driven kinase dependence. EGFR × MET BsAbs have demonstrated clinical activity in broad post-osimertinib EGFR-mutant NSCLC, while EGFR/MET co-dependence or MET-mediated bypass activation provides a mechanistic rationale for their use; MET-defined preferential benefit remains to be prospectively established. MET-directed antibody-drug conjugates (MET-ADCs) are supported in drug- and assay-defined populations with high c-MET protein overexpression, although the predictive relevance of delivery-related factors remains hypothesis-generating. Accordingly, MET testing should shift from single-event detection to platform-oriented stratification: next-generation sequencing (NGS) for driver alterations and resistance profiles, fluorescence in situ hybridization (FISH) for high-level focal amplification, and immunohistochemistry (IHC) for surface expression relevant to antibody-based therapies. This framework is intended to organize current biological and clinical evidence rather than to replace drug-specific companion diagnostics, regulatory indications, or prospectively validated treatment-selection algorithms. Precision treatment of MET-aberrant NSCLC is thus moving from event-based drug selection toward mechanism-based therapeutic matching. Future priorities include standardizing biomarkers, defining optimal target populations, and aligning biological subtypes, diagnostic strategies, and therapeutic platforms.

Antibody-drug conjugate↗

PubMed2026

Isolation and identification of a highly oncogenic subgroup J avian leukosis virus strain from Chinese black chickens.

Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is a highly contagious pathogen that induces myelocytomas, hemangiomas, and other neoplastic diseases in chickens. Recently, ALV-J infection in Chinese local chicken breeds has increased, with enhanced pathogenicity, posing a severe threat to the local poultry industry. In March 2024, a tumor outbreak occurred on a Chinese black chicken farm in Heze City, China, causing lethargy, emaciation, and tumorigenesis in the eyes and legs of affected chickens. Necropsy revealed extensive yellow-white neoplasms disseminated across the sternum, ribs, vertebrae, and visceral organs. Pathological examinations revealed multiple tumor types, including myelocytomas, hemangiomas, fibromas, and reticulosarcomas in the affected chickens. In this study, nine ALV-J isolates were isolated and designated HZ0319-1 to HZ0319-9. All isolates possessed an identical full-genome length of 7,687 bp and exhibited high nucleotide sequence similarity, ranging from 99.8% to 99.9%, suggesting that they were closely related variants from the same outbreak. Nucleotide sequence analysis identified unique deletions and mutations in the gag, pol, and gp85 genes, leading to predicted conformational changes in the P2, P10, and SU proteins. In addition, HZ0319 showed deletions in the r-TM region and a large 125-nt deletion in the E element of the 3' untranslated region, leaving only a short conserved fragment. The representative isolate HZ0319-1 showed stronger replication capacity than the reference strain NX0101 in DF-1 cells. In experimentally infected chicks, HZ0319-1 induced myelocytomas and hemangiomas and produced high viral load in multiple tissues. Notably, viral load analysis revealed that the liver showed the highest viral load at 1 day of age, whereas most other tissues reached peak viral load at 21 days of age, suggesting early hepatic replication followed by systemic dissemination. Furthermore, HZ0319-1infection significantly upregulated tumor-related host genes, including p53, c-Myc, c-Fos, and ZIC1, in tumor-associated tissues. These results demonstrate that the HZ0319-1 isolate has enhanced tumorigenicity and replication ability. Nucleotide mutations and deletions in both coding and non-coding regions of the viral genome may alter the viral tissue tropism and oncogenic potential. This study provides novel insights into the molecular characteristics and pathogenicity of ALV-J in local Chinese chickens, and provides a foundation for the prevention and eradication of ALV-J in the local poultry industry.

Avian leukosis virus subgroup J↗

PubMed2026

Development of an Efficient Regeneration and Agrobacterium-Mediated Transformation Protocol for Hosta 'Light Star' Using the RUBY Reporter Gene.

Hosta plantaginea is a perennial shade-tolerant herb of the Liliaceae family, with high ornamental and urban greening value. Hosta 'Light Star' is a newly developed ornamental cultivar with yellow-margined leaves and lilac flowers, but no efficient in vitro regeneration or genetic transformation system has been established for this cultivar to date. In this study, we established a highly efficient in vitro regeneration system for Hosta 'Light Star,' and developed an Agrobacterium-mediated genetic transformation protocol using the RUBY visual reporter gene for non-invasive screening of positive transformants. The optimal callus induction medium was MS + 2 mg/L 6-BA + 0.3 mg/L NAA + 0.05 mg/L 2, 4-D, with a callus induction rate of 53.33% for leaf explants (the optimal explant for sterile seedlings). The optimal adventitious bud proliferation medium was MS + 2 mg/L 6-BA + 0.1 mg/L NAA, with a proliferation coefficient of 5.87. The optimal rooting medium was 1/2 MS + 0.5 mg/L NAA + 0.5 mg/L IBA, with a 100% rooting rate. The optimal transplant substrate was perlite:vermiculite = 2:1, with a 100% transplant survival rate after acclimatization. For Agrobacterium-mediated transformation, the optimal infection parameters were as follows: Agrobacterium suspension OD600 = 0.6, infection time of 10 min, and 200 μM acetosyringone; the optimal selection conditions were 300 mg/L cefotaxime for bacteriostasis and 30 mg/L hygromycin for transformant screening. The final stable transformation efficiency was 2.50% (95% CI 1.23-3.77%), with an escape rate of 16.13%. Transgenic plants showed distinct purplish-red coloration in roots, stems, and leaves, with significantly higher betacyanin accumulation than wild-type plants (p < 0.05). Stable integration and expression of the RUBY gene were confirmed by PCR, RT-PCR, and RT-qPCR. This study establishes the first efficient regeneration and Agrobacterium-mediated transformation system for Hosta 'Light Star,' and validates the feasibility of the RUBY reporter gene as a visual marker for Hosta transformation. This system provides a solid technical platform for functional genomic studies, CRISPR/Cas9-mediated gene editing, and molecular breeding of ornamental traits in Hosta.

Transformation, Genetic↗

PubMed2025

Structure-activity relationships study on inhibition of CRISPR-Cas9 by glycosaminoglycans.

The CRISPR-Cas9 system is a revolutionary genome editing system known for its precision, simplicity and efficiency, playing a crucial role in gene-editing. It has enabled applications ranging from biomedicine to agriculture. However, the uncontrollable activity of Cas9 has raised significant safety concerns in clinical settings, limiting its broader application. Consequently, regulating CRISPR-Cas9 activity holds substantial promise for enhancing the safety and efficacy of gene-editing technologies. In this study, we demonstrated that sulfated glycosaminoglycans (GAGs) exhibit inhibitory effects of Cas9. Specifically, both chondroitin sulfate (CS) and heparin (HP) can inhibit CRISPR/Cas9 activity, with heparin showing a stronger inhibitory effect that correlates positively with its concentration. Molecular dynamics simulations indicate that sulfated heparin residues might inhibit Cas9 function by binding to essential DNA-binding sites, which are crucial for functional interactions, potentially impairing activity. Additionally, higher molecular weight GAGs exhibit enhanced inhibitory effects under the same sulphation. Notably, the sulfation site also influenced activity. C6-sulfation of chondroitin sulfate is more favorable for Cas9 inhibition, and N-sulfation of heparin enhances its inhibitory effect on Cas9 activity. These findings provide valuable insights into the development of carbohydrate-based inhibitors for CRISPR-Cas9, offering a foundation for further exploration in this field.

CRISPR-Cas Systems↗

PubMed2025

Exploring diagnostic m6A regulators in primary open-angle glaucoma: insight from gene signature and possible mechanisms by which key genes function.

PURPOSE: The purpose of this study was to interrogate the potential role of N6-methyladenosine (m6A) regulators in the process of trabecular meshwork (TM) tissue damage in patients with primary open-angle glaucoma (POAG). METHODS: Firstly, the expression profile of m6A regulators in TM tissues of POAG patients was comprehensively analyzed by bioinformatics analysis; Plasmid transfection and siRNA gene interference were used to enhance or weaken the expression levels of YTHDC2 in human trabecular meshwork cells (HTMCs); Cell migration ability was detected by transwell chamber assay; Immunofluorescence staining assay was used to evaluate the expression of extracellular matrix (ECM) related proteins. RESULTS: Through the analysis of GSE27276 database, 5 m6A regulators with different expression in POAG were screened out. The results of random forest model showed that these 5 m6A regulators exhibited diagnostic potential and were characteristic genes of POAG. All POAG samples could be effectively divided into two groups based on the expression levels of these 5 hub m6A regulators. Immune cell infiltration analysis indicated that the levels of activated CD8+ T cells and regulatory T cells were different in the two subtypes. HTMC oxidative stress cell model and TGF-β2 stimulation cell model were further constructed to verify the expression of the aforementioned hub m6A regulators, and it was found that YTHDC2 mRNA showed the same expression trend in both models. The silencing of YTHDC2 enhanced the migration ability of HTMCs and increased the synthesis ability of ECM. However, when YTHDC2ΔYTH, which lacks the YTH domain, is overexpressed in HTMCs, there is no significant change in the ECM synthesis ability. CONCLUSIONS: The differentially expressed m6A regulators in TM tissues may serve as potential diagnostic biomarkers for POAG. And, in HTMCs, the expression level of YTHDC2 mRNA was changed under oxidative stress or TGF-β2 intervention, and then exerted its regulation on cell migration and ECM synthesis capability through m6A modification, which may be an important part of the disease process of POAG.

Humans↗