Biomedical subjects

Xiang Zhang

Publications and source records attributed to Xiang Zhang.

8 recordsLinked to original sources

PubMed2026

Single-cell and spatial transcriptomics define a progenitor subpopulation and fibroinflammatory niche at the leading edge of parathyroid carcinoma.

Parathyroid carcinoma (PC) is a rare but clinically aggressive endocrine malignancy with limited treatment options and a poorly defined tumor microenvironment (TME). To elucidate its cellular heterogeneity and spatial architecture, we integrated single-cell and spatial transcriptomic profiling with whole-exome sequencing and multiplex immunohistochemistry on eight parathyroid neoplasm specimens, including PC, parathyroid adenoma, and atypical parathyroid tumor. We identified a distinct progenitor-like endocrine subpopulation (Ca-1) enriched in CDC73-mutant PC, exhibiting stem-like properties, elevated cell cycle activity, and pronounced genomic instability. Spatial mapping revealed that Ca-1 cells preferentially localize at the leading edge, forming a fibroinflammatory niche characterized by the enrichment of inflammatory cancer-associated fibroblasts (iCAFs) and SPP1+ macrophages. Within this niche, the dipeptidyl peptidase 4 (DPP4) is selectively expressed in Ca-1 cells and iCAFs, implicating a potential paracrine axis driving stromal remodeling and immunosuppression. These findings suggest that a spatially organized ecosystem may promote PC progression through TME remodeling and highlight the DPP4-CXCL2 axis as a candidate pathway for future investigation in aggressive parathyroid neoplasms.

Humans↗

PubMed2026

Bilateral Conversion Risk in Unilateral Retinoblastoma Using Age and Genetic Testing.

IMPORTANCE: Metachronous bilateral conversion in initially unilateral retinoblastoma is uncommon but clinically consequential, potentially requiring intensified treatment and carrying worse prognosis. Clarifying how age at diagnosis refines genetic-risk stratification could enable safer, more efficient surveillance protocols. OBJECTIVE: To estimate the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma and assess whether age at diagnosis and RB1 testing are associated with bilateral conversion risk. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study at a tertiary center in Shanghai, China, including 1108 consecutive children with initially unilateral retinoblastoma diagnosed from July 2010 to October 2024 (after exclusions for short follow-up [n = 139], missing data [n = 53], or synchronous bilateral disease [n = 10]). The median (IQR) follow-up was 43.4 (24.2-67.6) months. EXPOSURES: Age at diagnosis and RB1 genetic status/subtypes assessed by next-generation sequencing and multiplex ligation-dependent probe amplification, including penetrance class (high vs low) and mosaic vs germline categorization. MAIN OUTCOMES AND MEASURES: Time to metachronous bilateral conversion; cumulative incidence functions with death as a competing risk; spatial distribution of fellow-eye tumors. RESULTS: Among 1108 patients (median [IQR] age at diagnosis, 22.2 [12.0-31.4] months; 591 [53.3%] male), 24 (2.2%) developed metachronous bilateral disease. At 24 months, cumulative incidence was 2.2% (95% CI, 1.3-3.1) overall. By genetic status, the 24-month cumulative incidence was 24.8% (95% CI, 13.8-35.9) in RB1 variant-positive vs 1.6% (95% CI, 0.0-3.1) in RB1 variant-negative patients. Among RB1 variant-positive patients, risk clustered among those diagnosed before 9 months, whereas no conversions were observed among those diagnosed at older than 9 months. Four RB1 variant-negative patients who were initially diagnosed at notably late ages (20.9, 42.7, 79.6, and 118 months) subsequently converted; these cases likely represent undetected low-level mosaicism, somatic variants below detection thresholds, or rare genomic events not captured by standard sequencing panels. Fellow-eye tumors did not involve macula and showed a nasal-predominant distribution. CONCLUSIONS AND RELEVANCE: The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.

Humans↗

PubMed2026

CaMYB121-CaABF2 negative feedback loop modulates CaNHX2 expression to confer salt tolerance in pepper.

Salt stress is a major abiotic factor that severely restricts pepper (Capsicum annuum) production. Although abscisic acid (ABA) is vital for salt tolerance, the transcriptional regulatory networks governing ABA-mediated salt defense remain largely unknown. Here, we uncovered a negative feedback loop between CaMYB121 and CaABF2.1/2 that modulates the expression of CaNHX2.1/2/3, thereby enhancing salt tolerance in pepper plants. RNA-seq analysis revealed that CaMYB121 displayed an expression pattern consistent with that of CaNHX2 after salt treatment. Silencing CaMYB121 markedly reduced salt tolerance and inhibited root growth. Mechanistically, CaMYB121 directly binds to the CaNHX2 promoter to activate transcription, thereby promoting salt resilience. Salt stress also robustly triggered ABA signaling genes, with CaABF2.1/2 displaying expression patterns closely mirroring those of CaMYB121. Transient silencing of CaABF2.1/2 results in phenotypes similar to those observed with CaMYB121 suppression. Notably, CaMYB121 activates CaABF2.1/2 transcription by binding to its promoters, whereas CaABF2.1/2 represses CaMYB121 expression by directly targeting its promoter, forming a self-regulating feedback loop that prevents excessive defense activation. Collectively, our findings reveal a CaMYB121-CaABF2 feedback circuit that dynamically balances growth and defense to optimize salt tolerance in pepper plants.

Salt Tolerance↗

PubMed2025

Rat somatic genome editing enables ER+ breast cancer modeling.

Genetically engineered mouse models have advanced cancer research but often fail to capture key features of certain human tumors. Rats, with distinct physiology and tumor biology, offer a powerful alternative, yet their use has been constrained by technical barriers to genome editing. Here, we report efficient somatic genome editing in rats, enabling both Indel and substitution mutations. We then apply this approach to model estrogen receptor (ER)-positive breast cancer, which accounts for ~70% of human cases but remains poorly represented in mice. The resulting rat tumors reproduce hallmarks of human ER+ breast cancer, including ductal histology, hormone responsiveness, and immune-microenvironmental features. By contrast, identical genetic alterations in mice failed to yield ER+ tumors, underscoring critical species differences in tumorigenesis. Together, this work establishes a versatile platform for rapid generation of clinically relevant rat tumor models, opening new avenues to dissect tumor biology, therapeutic response, and immune interactions in previously inaccessible cancer subtypes.

Journal Article↗

PubMed2025

Streptomyces huangiella sp. nov., an endophytic actinomycete isolated from Pheretima aspergillum, a promising candidate for biological pathogen control.

UNLABELLED: Pheretima aspergillum (E. Perrier) is an annelid of the genus Pheretima in the family Megascolecidae, a species of earthworm, whose dried body (Guang Dilong) is a traditional Chinese animal medicine. A new actinobacterium strain, named HD1123-B1T, was isolated from the gut contents of Pheretima aspergillum caught in the wild in Guangzhou, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain was primarily identified as a member of the genus Streptomyces, sharing more than 98% sequence identity to Streptomyces endocoffeicus CA3R110T (98.80%), Streptomyces coffeae CA1R205T (98.47%), and Streptomyces iranensis HM35T (97.93%). The whole genome size of strain HD1123-B1T was approximately 8.9 Mbp, with 7,464 predicted genes and 71.42 mol% DNA C+G content. Comparative genomic analyses based on digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values revealed that strain HD1123-B1T represents a novel species within the genus Streptomyces. Additionally, 38 biosynthetic gene clusters for secondary metabolites were also predicted in the genome of strain HD1123-B1T. Based on LC-MS/MS analysis, the nigericin biosynthesis gene cluster has been completely characterized. The ethyl acetate crude extract of strain HD1123-B1T exhibited remarkable antibacterial activity against gram-positive bacteria (methicillin-resistant Staphylococcus aureus ATCC 25213, etc) and gram-negative bacteria Ralstonia solanacearum GIM 1.70. Based on these results, HD1123-B1T could be confirmed as an isolate that represents a novel species of the genus Streptomyces, for which the name Streptomyces huangiella sp. nov. is proposed. IMPORTANCE: As the largest genus of the phylum Actinomycetes, Streptomyces is a kind of microbial resources with great practical and economic value. Due to their unique physiological properties and metabolic capacity, Streptomyces have become an important source of bioactive compounds in the world and play an indispensable role in medical and industrial fields. With the advancement of molecular biology and genomics, researchers can more deeply explore the metabolic potential of Actinomycetes, discovering and developing new biologically active compounds. These new compounds may possess various biological activities, such as antibacterial, antiviral, antifungal, and antiparasitic properties, further promoting the development of medicine and related industries. Based on genomic analysis and antibacterial activity, the strain HD1123-B1T was indicated to be a promising candidate for biological pathogen control.

Streptomyces↗

PubMed2025

Abnormal levels of miRNA in pancreatic cancer are linked to tumor progression by regulating the translation of tumor-associated mRNA.

BACKGROUND: Pancreatic cancer remains one of the most malignant tumors, characterized by limited treatment efficacy. MAIN FINDINGS: microRNAs (miRNAs) play a crucial role in regulating the proliferation, invasion, migration, drug resistance, apoptosis, and cell cycle progression of pancreatic cancer cells by inhibiting tumor-associated proteins. Metscape analysis revealed that miRNA-targeted proteins associated with pancreatic cancer are enriched in processes such as cell proliferation, mitosis, and cell migration, and participate in multiple signaling pathways. These proteins primarily localize to classical pathways, including JAK/STAT, PI3K/AKT, and Wnt/β-catenin. Furthermore, gene mutations or abnormal alternative poly(A)denylation (APA) within miRNA-targeted regions can disrupt base pairing to the 3'-Untranslated Region (3'-UTR), thereby enhancing the translation of oncogenic mRNA translation. FUTURE DIRECTIONS: Collectively, these findings indicate that multiple miRNAs act cooperatively to influence pancreatic cancer progression. Consequently, therapeutic strategies aimed at restoring the balance of the miRNA system are essential to disrupt the 'mRNA-oncogene' vicious cycle.

Humans↗

PubMed2024

Integrative Omics Reveals the Metabolic Patterns During Oocyte Growth.

Well-controlled metabolism is associated with high-quality oocytes and optimal development of a healthy embryo. However, the metabolic framework that controls mammalian oocyte growth remains unknown. In the present study, we comprehensively depict the temporal metabolic dynamics of mouse oocytes during in vivo growth through the integrated analysis of metabolomics and proteomics. Many novel metabolic features are discovered during this process. Of note, glycolysis is enhanced, and oxidative phosphorylation capacity is reduced in the growing oocytes, presenting a Warburg-like metabolic program. For nucleotide biosynthesis, the salvage pathway is markedly activated during oocyte growth, whereas the de novo pathway is evidently suppressed. Fatty acid synthesis and channeling into phosphoinositides are specifically elevated in oocytes accompanying primordial follicle activation; nevertheless, fatty acid oxidation is reduced in these oocytes simultaneously. Our data establish the metabolic landscape during in vivo oocyte growth and serve as a broad resource for probing mammalian oocyte metabolism.

Animals↗

PubMed2024

A statistical simulation model to guide the choices of analytical methods in arrayed CRISPR screen experiments.

An arrayed CRISPR screen is a high-throughput functional genomic screening method, which typically uses 384 well plates and has different gene knockouts in different wells. Despite various computational workflows, there is currently no systematic way to find what is a good workflow for arrayed CRISPR screening data analysis. To guide this choice, we developed a statistical simulation model that mimics the data generating process of arrayed CRISPR screening experiments. Our model is flexible and can simulate effects on phenotypic readouts of various experimental factors, such as the effect size of gene editing, as well as biological and technical variations. With two examples, we showed that the simulation model can assist making principled choice of normalization and hit calling method for the arrayed CRISPR data analysis. This simulation model is implemented in an R package and can be downloaded from Github.

CRISPR-Cas Systems↗