Biomedical subjects

Xiaoming Zhang

Publications and source records attributed to Xiaoming Zhang.

4 recordsLinked to original sources

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

Plasma Proteomics Identifies Thousand-and-One-Amino Acid Kinase 3 as a Potential Biomarker of Rheumatoid Arthritis Activity and a Novel Therapeutic Target.

OBJECTIVE: Bone destruction associated with active rheumatoid arthritis (RA) remains a major therapeutic challenge, with a lack of reliable molecular markers reflecting bone injury. This study aims to identify novel biomarkers linked to bone destruction in active RA through proteomic analysis, providing new strategies for precise monitoring and targeted therapy. METHODS: Data-independent acquisition mass spectrometry was used for proteomic quantification and bioinformatic analysis on plasma samples from 160 patients with RA and 40 healthy controls. Key proteins associated with bone destruction were screened by integrating Sharp scores with synovial single-cell RNA sequencing data and subsequently validated in two independent cohorts (N1 = 50 and N2 = 10) using enzyme-linked immunosorbent assay and multiplex immunohistochemistry. Functional studies were conducted using fibroblast-like synoviocytes (FLSs) in vitro and a collagen-induced arthritis (CIA) mouse model in vivo. RESULTS: A total of 4,998 plasma proteins were identified, with 506 showing significant differential expression between active and remitted RA. Thousand-and-one-amino acid kinase 3 (TAOK3) levels were positively associated with Sharp scores and markedly elevated in patients with active RA. Combining TAOK3 with C-reactive protein improved diagnostic accuracy for active RA (area under the curve = 0.915). High TAOK3 expression was also associated with increased relapse frequency. Functional studies showed that TAOK3 knockdown suppressed the tumor-like phenotype of FLSs and down-regulated matrix metalloproteinase 1/2/3 and cathepsin K, whereas TAOK3 overexpression promoted pannus cell-mediated bone erosion, mitigated by TAOK3-targeted inhibitor. In vivo, its inhibition showed therapeutic effects in CIA mice. CONCLUSION: TAOK3 serves as a potential biomarker for bone destruction in active RA and as a therapeutic target for precision monitoring and intervention.

Arthritis, Rheumatoid↗

PubMed2025

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression. Thus, a major question is how to modulate the phenotype and function of microglia to treat AD. Xenon (Xe) gas is a noble gas used in human patients as an anesthetic and a neuroprotectant used for treating brain injuries. Xe penetrates the blood-brain barrier, which could make it an effective therapeutic. To assess the effect of Xe on microglia and AD pathology, we designed a custom Xe inhalation chamber and treated several mouse models of AD with Xe gas. Xe treatment induced mouse microglia to adopt an intermediate activation state that we have termed pre-neurodegenerative microglia (pre-MGnD). This microglial phenotypic transition was observed in mouse models of acute neurodegeneration and amyloidosis (APP/PS1 and 5xFAD mice) and tauopathy (P301S mice). This microglial state enhanced amyloid plaque compaction and reduced dystrophic neurites in the APP/PS1 and 5xFAD mouse models. Moreover, Xe inhalation reduced brain atrophy and neuroinflammation and improved nest-building behavior in P301S mice. Mechanistically, Xe inhalation induced homeostatic brain microglia toward a pre-MGnD state through IFN-γ signaling that maintained the microglial phagocytic response in APP/PS1 and 5xFAD mice while suppressing the microglial proinflammatory phenotype in P301S mice. These results support the translation of Xe inhalation as an approach for treating AD.

Animals↗

PubMed2025

Small interfering RNAs generated from the terminal panhandle structure of negative-strand RNA virus promote viral infection.

Virus-derived small interfering RNAs (vsiRNAs) have been widely recognized to play an antiviral immunity role. However, it is unclear whether vsiRNAs can also play a positive role in viral infection. Here, we characterized three highly abundant vsiRNAs mapped to the genomic termini of rice stripe virus (RSV), a negative-strand RNA virus transmitted by insect vectors. The three vsiRNAs shared 11 nucleotides due to the conservative genomic termini and were likely generated from viral terminal panhandle structure, depending on both Dicer1 and Dicer2 in insects. In addition to targeting viral RNAs in a miRNA-like manner, the three vsiRNAs coordinately downregulated the expression of DOPA decarboxylase, thereby suppressing the prophenoloxidase immune reaction in insect vectors. In vsiRNA-silenced transgenic rice, the viral titer significantly decreased, indicating that these vsiRNAs promote RSV replication in rice. This study elucidates a unique function of vsiRNAs derived from the conserved panhandle structure of negative-strand RNA viruses in enhancing viral infection.

RNA, Small Interfering↗