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Biomedical subjects

Sihan Chen

Publications and source records attributed to Sihan Chen.

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

Genetic Contributors to Postoperative Delirium and Their Implications for Dementia Outcomes.

BACKGROUND: Postoperative delirium (POD) is a perioperative neurocognitive disorder that substantially impairs patient recovery. Unfortunately, its genetic risk profile and relationship with subsequent dementia remain unclear. This study aimed to elucidate genetic contributors to POD identified via Hospital Episode Statistics codes and to examine its association with subsequent dementia. METHODS: The study included 230,179 noncardiac and 21,254 cardiac surgery subjects from the UK Biobank, defining POD using delirium codes from the International Classification of Diseases (10th revision) recorded within the first 7 postoperative days. Genome-wide association studies were performed in the noncardiac and cardiac cohorts and their prespecified subgroups, followed by functional annotation, gene prioritization and drug-target analyses. Associations between POD and subsequent dementia were estimated using Cox models. RESULTS: In the noncardiac cohort, one genome-wide significant locus was identified at the APOE region, with rs429358 as the lead variant ( P = 5.00 × 10 -28 ). Integrative gene prioritization analyses highlighted multiple genes within this locus. Exploratory drug-target analyses suggested potential subgroup-specific drug-target enrichment. In the cardiac cohort, no genome-wide significant signals were detected. POD was associated with all-cause dementia after both noncardiac (hazard ratio, 6.45; 95% CI, 5.45 to 7.63) and cardiac (hazard ratio, 2.95; 95% CI, 1.71 to 5.08) surgeries. CONCLUSIONS: This study demonstrates APOE as a genetic risk locus for International Classification of Diseases-coded POD in the noncardiac surgery setting and confirms an association between POD and subsequent dementia.

Humans