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Biomedical subjects

Zhifeng Xu

Publications and source records attributed to Zhifeng Xu.

2 recordsLinked to original sources

Sex-specific expression of detoxification proteins contributes to differential metabolic detoxification capacity and acaricide sensitivity in female and male Tetranychus cinnabarinus (Boisduval).

Pronounced sex-specific differences exist in the toxicological traits of spider mite species. Our previous work showed that female Tetranychus cinnabarinus exhibit significantly higher tolerance to acaricides than males, primarily driven by elevated detoxification enzyme activity. However, the molecular basis underlying this sex-specific difference remains unclear. Here, we used pyridaben and cyflumetofen as representative acaricides to dissect the molecular mechanisms underlying sex-specific differences in detoxification metabolism between female and male mites. After 48 h of cyflumetofen exposure, GST activity increased significantly in female mites. Following pyridaben exposure, the activities of both P450 (24 h and 48 h) and CCE (48 h) increased significantly in female mites. Under the same conditions, only P450 activity increased significantly in male mites after 48 h of pyridaben exposure. Proteomic profiling identified 33 differentially expressed detoxification enzymes, predominantly from the major detoxification families P450, GST, and CCE; among them, 26 were significantly upregulated in females relative to males. Six detoxification enzymes, including CYP392A3, CYP389C5, TcGSTd02, TcGSTd13, TcCCE39, and TcCCE52, were selected for functional characterization. We successfully obtained six active recombinant detoxification enzymes through heterologous expression. IC50 and in vitro metabolism assays showed that these recombinant proteins display both shared and distinct capacities for metabolizing or sequestering cyflumetofen and pyridaben. RNAi and bioassay results demonstrated that silencing CYP389C5, TcGSTd02, and TcCCE52 resulted in more pronounced changes in acaricide susceptibility in female than in male mites. Collectively, this study demonstrates that the sex-biased protein abundance identifies candidate biochemical contributors to differential susceptibility in female and male mites.

Animals

Pathogenic role of serpin B3-positive neutrophils in reinforcing thrombus stiffening during ischemic stroke.

The contribution of immune cells to thrombus architecture and mechanical properties in acute ischemic stroke (AIS) remains poorly understood. Using 3-dimensional imaging and multiplex staining, we mapped immune cells in human stroke thrombi and identified neutrophils as the dominant population. Analysis of 19 thrombi confirmed their positive correlation with collagen, increased stiffness, and poorer clinical outcomes. To preserve spatial context, we developed a laser capture-based proteomic workflow and analyzed thrombus neutrophils from 34 patients with AIS stratified by 90-day outcomes, followed by validation in an independent cohort of 22 patients. Proteomic analysis revealed serpin B3 as a neutrophil-enriched protein strongly correlated with poor prognosis. In murine models of ferric chloride-induced carotid artery thrombosis and middle cerebral artery occlusion, experiments using wild-type, neutrophil-depleted, and Serpinb3a knockout mice demonstrated that neutrophil-derived serpin B3 promotes early thrombus formation, enhances collagen deposition, and contributes to progressive thrombus stiffening. Mechanistically, serpin B3 secreted by neutrophils amplifies thrombus stiffness through upregulation of transforming growth factor β1, neutrophil extracellular traps, and COL1A1. Targeted Serpinb3a knockdown delayed vascular occlusion, improved thrombolysis efficiency, and resulted in better neurological recovery. Collectively, these findings identify a neutrophil-driven mechanism underlying thrombus stiffening and establish SERPINB3 as both a prognostic biomarker and a promising therapeutic target in AIS. This project has been registered with the Chinese Clinical Trial Registration Platform (https://www.chictr.org.cn/index.html) and has successfully passed the review process (registration number: ChiCTR2300077911).

Animals