Biomedical subjects

Xinyi Zhang

Publications and source records attributed to Xinyi Zhang.

5 recordsLinked to original sources

PubMed2026

Spatial isoform sequencing at single-cell resolution reveals cell-type-specific spatial isoform variability in multiple brain cell types.

Spatial long-read technologies are increasingly common but usually lack single-cell resolution. This leaves unanswered whether spatially variable isoforms reflect variability within one cell type or differences in region-specific cell-type composition. Here, we developed Spl-ISO-Seq2 (500-nm resolution) and accompanying software, Spl-IsoQuant-2 and Spl-IsoFind, enabling long-read sequencing of >450 million barcodes versus 80,000 previously. Applying this to the adult mouse brain, we compared differential isoform abundance between known regions and spatial isoform patterns independent of predefined regions. Both identified overlapping hits, for example, Rps24 in oligodendrocytes. For known Snap25 spatial isoform variation, we show that it occurs in excitatory neurons. The region-agnostic approach also uncovered patterns missed by region-based comparisons, for example, for Ighm. Notably, many spatial isoform signals are not driven by cell-type composition alone. Finally, our software is applicable to many spatial and single-cell protocols, demonstrating reproducibility between platforms (for example, Visium HD/Stereo-seq). Overall, our experimental/analytical methods enable a submicron-resolution-isoform view and open avenues for spatial isoform disease research.

Animals↗

PubMed2026

Mulberry-derived endophytic Bacillus velezensis suppresses gray mold and promotes mulberry growth via reshaping the root metabolism and microbiome.

INTRODUCTION: Gray mold is an important fungal disease caused by Botrytis cinerea which threatens global agriculture. As chemical control faces limitations, biological control using Bacillus has gained attention for its environmental friendliness and growth promotion. However, their ecological basis and application potential in mulberry gray mold control remain insufficiently understood. OBJECTIVE: This study aimed to evaluate the biocontrol efficacy of the mulberry derived endophytic strain Bacillus velezensis ZJU_268 and to investigate its associated effects on plant growth, root-associated microbiomes, and metabolic profiles. METHODS: Greenhouse assays were combined with genomic and comparative genomic analyses, amplicon sequencing, non-targeted metabolomics, and functional validation of isolated microbes and metabolites to assess the effects of ZJU_268 and its cell free supernatant (CFS) on mulberry seedlings. RESULTS: This study isolated a mulberry derived endophytic bacterium, B. velezensis ZJU_268, which exhibits strong antifungal activity and reduces the incidence of gray mold in mulberry seedlings. Whole-genome sequencing and comparative genomic analyses revealed strain-specific regions and genes associated with root colonization, stress adaptation, and antimicrobial biosynthesis. Both live cells and CFS significantly promoted seed germination, seedling growth, and biomass accumulation in a dose dependent manner. Amplicon sequencing showed that ZJU_268 and its supernatant reshaped the mulberry root microbiome, enriching beneficial bacterial and fungal taxa while reducing potentially pathogenic members. Cultivable members of the enriched microbiota displayed strong antifungal activity against B. cinerea and promoted mulberry growth. Metabolomic profiling further showed that ZJU_268 and its supernatant were associated with marked metabolic shifts in mulberry roots, accompanied by the accumulation of selected metabolites that supported the growth of representative enriched isolates. CONCLUSIONS: This study demonstrates that ZJU_268 suppresses gray mold and promotes mulberry growth in association with direct antagonistic activity, microbiome restructuring, and holobiont-level metabolic shifts, providing a promising biological strategy for sustainable mulberry disease management.

Bacillusvelezensis↗

PubMed2026

Association between the interleukin 17F rs763780 polymorphism and immune thrombocytopenia risk: A systematic review and meta-analysis.

The literature on the Interleukin 17F (IL-17F) rs763780 polymorphism and its association with immune thrombocytopenia (ITP) risk remains inconsistent and controversial. These uncertainties underscore the urgent need for a meta-analysis to objectively synthesize the heterogeneous findings, mitigate bias, and improve statistical power. This study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines. A systematic literature search for original studies was conducted across the CNKI, Wanfang Data, Cochrane Library, Web of Science, and PubMed databases, covering publications up to April 5, 2026. Odds ratios and corresponding 95% confidence intervals were calculated to assess the association. STATA 14.2 software was used to synthesize the pooled estimates. A total of eight case-control studies consisting of 805 ITP cases and 841 controls were included. The summarized statistics suggested the detrimental effect of the A allele in the homozygote and recessive models. In the sensitivity analysis, the results that were initially non-significant in the allele, heterozygote, and dominant models became significant after excluding a single dataset, which was also identified as the source of heterogeneity. Region-stratified analyses revealed statistical significance in the Chinese/Japanese and Egyptian subgroups under specific analytic contrasts. When stratified according to age, the children subgroup showed significant associations in a subset of genetic models, while the adult counterpart demonstrated significance across all models. In conclusion, the pooled estimates of the homozygote and recessive models suggested that the rs763780 polymorphism is associated with ITP risk, but this finding requires further validation through large-scale studies.

Humans↗

PubMed2026

Proteogenomic features define subtypes of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. Although genomics and transcriptomics have delineated parts of the MCL disease spectrum, proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 patients with MCL and 4 healthy donors to investigate the translational and posttranslational dimensions of MCL. Our study identified 1296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed immunoglobulin heavy chain variable mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multiomics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared with single-omics models (concordance index, 0.83 vs 0.74). This study provides, to our knowledge, the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.

Humans↗

PubMed2026

Combinatorial base editing couples disease correction with lineage amplification in hematopoietic stem and progenitor cells.

First-generation genome editing therapies have largely focused on correcting or compensating for pathogenic variants. However, as these approaches enter the clinic, emerging biological constraints limit maximal therapeutic impact. Because globin genes are activated late during erythroid differentiation, genome-corrected hematopoietic stem and progenitor cells (HSPCs) gain little selective advantage in the bone marrow. Here, we establish a strategy that links therapeutic genome edits to an erythroid fitness-enhancing allele to amplify the output of clinically relevant cells. We develop a multiplex base editing strategy that couples fetal hemoglobin (HbF) reactivation with erythroid lineage expansion. Introduction of a naturally occurring erythropoietin receptor truncation (tEPOR) associated with benign erythrocytosis increased erythroid cell production without impairing viability or differentiation. Combinatorial editing of tEPOR together with the BCL11A erythroid enhancer and HBG1/2 promoters in healthy donor, sickle cell disease, and β-thalassemia HSPCs synergistically increased erythroid proliferation and HbF expression beyond single base-edited or Casgevy-treated controls. Multiplex base-edited HSPCs retained long-term lineage repopulation and engraftment capacity in vivo, establishing a modular strategy that pairs disease correction with lineage amplification to improve therapeutic potency.

Journal Article↗