Biology subjects

ZHAO, M.

Publications and source records attributed to ZHAO, M..

4 recordsLinked to original sources

bioRxiv2026

MXRA7 Alleviates Epididymitis from Exercise-Induced Fatigue by Inhibiting Pyroptosis

AimsTo explore exercise-induced fatigue (EIF)s effects on the male reproductive system and MXRA7s regulatory role herein. MethodsWe recruited EIF volunteers for semen/serum tests, established a mouse EIF model via weight-loaded swimming to assess epididymal segmental injury, and constructed pyroptosis models of PC-1/DC-2 cells. Public database transcriptomic analysis identified MXRA7 expression and enriched pathways in epididymitis; MXRA7s function was verified via its knockdown/overexpression in DC-2 cells. PKC-MXRA7 association was explored by phosphorylation assays and CO-IP, and sperm incubation experiments evaluated MXRA7s effect on sperm function. ResultsEIF impaired human sperm motility, reduced mouse sperm quality and induced epididymitis with segment-specific pyroptosis. MXRA7 expression differed in PC-1/DC-2 cells and correlated with pyroptosis; it was phosphorylated by PKC, inhibited the NF-{kappa}B pathway to alleviate inflammation, and mitigated pyroptosis-induced sperm motility damage. ConclusionEIF induces epididymal epithelial pyroptosis and epididymitis, and MXRA7 exerts a protective effect mainly in caudal epididymal cells by alleviating pyroptosis, thus reducing sperm quality damage.

molecular biology↗

bioRxiv2025

Ionizing Radiation Shapes Genome Evolution Through Nuclear Abnormalities That Trigger Delayed Proliferative Death

Ionizing radiation (IR) is widely used in cancer therapy, yet the mechanisms by which IR-induced DNA damage translates into delayed proliferative death and secondary malignancy risk remain incompletely defined. Radiation generates double-strand breaks (DSBs) that are frequently misrepaired, giving rise to micronuclei and chromosome bridges--abnormal nuclear structures known to drive chromosomal instability. Here, a modified live-cell imaging and single-cell whole-genome sequencing (WGS) approach was used to directly connect early cytological responses to genome-wide outcomes in cells exposed to graded IR doses. Tracking asynchronously cycling cells revealed that micronuclei, chromosome bridges, and nuclear fragmentation form at high frequency during the first mitosis after irradiation, in a strongly cell-cycle-dependent manner: micronuclei were most frequent after S-phase irradiation, whereas chromosome bridges predominated when damage occurred in G1 or S phase. Lineage tracing combined with clonogenic assays showed that formation of abnormal nuclear structures in the first post-irradiation division is a major determinant of long-term proliferative capacity, with centromere-containing (centric) fragments and bridges exerting a stronger anti-proliferative effect than acentric micronuclei. Single-cell WGS of daughter and granddaughter cells demonstrated that these structures generate reciprocal copy-number changes, clustered rearrangements, and chromothripsis-like events that are largely incompatible with sustained proliferation. In contrast, bulk WGS of surviving single-cell-derived clones revealed only modest increases in single-nucleotide variants and indels but an enrichment of nonhomologous end-joining-associated deletion signatures and selected structural variants, including amplification of a pre-existing 12p gain. These findings identify abnormal nuclear structures as key intermediates linking IR-induced DNA lesions to mitotic catastrophe and provide insight into selective tolerance of specific rearrangements.

cell biology↗

bioRxiv2025

A novel rat model for human Meibomian gland dysfunction and ocular rosacea

Ocular Rosacea (OR) is a common chronic inflammatory disease that affects the ocular surface and eyelids. Meibomian gland dysfunction (MGD), often associated with OR, can lead to dry eye syndrome and vision-threatening corneal complications. OR is underdiagnosed and incurable, highlighting the need for a deeper understanding of the pathogenesis of MGD associated with OR to develop targeted treatments. In this study, rat upper eyelids were exposed to UVB, a known triggering factor for rosacea, for five days. UVB exposure caused acute damage to the eyelid skin and meibomian glands (MG) together with increased oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and elevated lipid production by day 5. During the two-week healing process, inflammation and lipid hyperproduction tended to normalize, but hyperkeratinization of MG ducts persisted, and meibocyte stem cells continued to decrease. This led to MGD and was likely responsible for corneal epithelial defects observed on day 19. The progressive fibrosis in rat MG was similar to that observed in MG biopsy tissues from OR patients, suggesting that UVB causes chronic and irreversible damage to MGs. Transcriptomic intersection analysis revealed shared gene regulation patterns between UVB-induced changes in rat MG and human rosacea and MGD. Additionally, UVB altered Meibum lipid composition in ways that mimic human MGD. This model provides a valuable tool for studying the pathophysiology of MGD associated with OR and for evaluating potential treatments.

pathology↗

bioRxiv2020

The PRC2-dependent epigenetic reprograming of the bladder epithelium exacerbates urinary tract infections

Mucosal imprint sensitizes recurrent urinary tract infections (UTIs), a significant health and quality of life burden worldwide, which are associated with heightened inflammatory host response, severe basal cell hyperplasia and impaired superficial cell differentiation. Here, we show that bladder infections induce expression of Ezh2, the methyltransferase of polycomb repressor complex 2 (PRC2)-dependent epigenetic gene silencing program. In mouse models of UTIs, urothelium-specific inactivation of PRC2 reduces the urine bacteria burden. The mutants exhibit a blunted inflammatory response likely due to the diminished activity of NF-{kappa}B signaling pathway. PRC2 inactivation also improves urothelial differentiation and attenuates basal cell hyperplasia phenotype. Moreover, the Ezh2-specific small molecule inhibitors markedly improve disease outcomes of bladder superinfection and chronic cystitis. Taken together, these findings suggest that the UTI-induced epigenetic reprograming in the bladder urothelium likely contributes to the mucosal imprint, and further suggest that targeting PRC2 methyltransferase offers a non-antibiotic strategy to mitigate UTIs.

immunology↗