Bin Wang

Heat stroke (HS) is the most severe heat-related emergency, and its pathophysiology remains largely unknown, especially for exertional HS (EHS), which affects younger populations, athletes, and manual workers. Herein, we performed single-cell-transcriptomics, T cell receptor sequencing, and flow cytometry of PBMCs from 9 healthy control participants, 9 patients with heat exhaustion, and 9 patients with EHS to explore complex immunological responses associated with HS pathobiology. We showcased that granzyme-positive T cells and CD56 ^dim NK cells with high cytotoxicity features and IL-1B ⁺ NLRP3 ⁺ monocytes with high inflammation and pyroptosis scores were enriched in HS, while the CD161 ⁺ T cells with innate immune-like, low cytotoxicity, and clonal expansion features were reduced in HS. Importantly, elevated granzyme-positive T and NK cells might interact with monocytes to induce pyroptosis of hepatic and renal cells and target organ injuries, and blocking the NLRP3 inflammasome pathway prior to the induction could alleviate organ injury in HS. This study offers deeper insights into the pathogenesis of HS, supporting the development of optimal treatment strategies.

Background: The relationship between kidney function and mortality in centenarians, particularly with respect to hormonal regulation, remains unclear. This study investigated the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in female centenarians and explored the potential role of testosterone. Methods: Within the China Hainan Centenarian Cohort Study, 701 female centenarians (median age: 102 years) were enrolled. eGFR was calculated using the CKD-EPI 2009 creatinine equation. Restricted cubic splines (RCSs) and multivariable Cox proportional hazards models were employed to assess nonlinear associations. Likelihood ratio tests were used to evaluate the interaction effect of testosterone. Results: During a median follow-up of 31 months, 643 participants (91.7%) died. RCS analysis revealed a significant nonlinear association (P-overall < 0.001; P-nonlinear = 0.004) between eGFR and all-cause mortality, characterized by a U-shaped curve, with an inflection point of 60.65 mL/min/1.73 m² identified in the adjusted RCS model. Multivariable-adjusted Cox regression analysis showed that each 10-mL/min/1.73 m² increase in eGFR was associated with a 6.8% reduction in all-cause mortality risk (hazard ratio = 0.932, 95% confidence interval: 0.882–0.985, P = 0.012). Compared with centenarians with eGFRs of 45–P < 0.001) and a significantly shorter median survival time (26 months vs. 34 months, P < 0.001). Higher testosterone levels attenuated the association between eGFR and all-cause mortality, indicating a protective effect (P for multivariable nonlinear interaction = 0.022). Conclusion: In female centenarians, lower eGFR (< 45 mL/min/1.73 m²) is independently associated with all-cause mortality, and this association is modified by serum testosterone levels. These findings highlight testosterone as a potential modulator of the kidney function–mortality relationship in centenarians, although the causal relationship requires further investigation.

Background: Metastasis is a major negative prognostic marker in clear cell renal cell carcinoma (ccRCC). Membrane palmitoylated proteins (MPPs) are a class of cell polarity-associated proteins that function in both cell-cell junction and adhesion. However, the relationship between MPP7 and the prognosis of ccRCC remains elusive. In this study, we aimed to investigate the associations between MPP7 expression with clinical prognosis of ccRCC using bioinformatics analyses. Methods: The messenger RNA (mRNA) and protein expression patterns of MPP7 in different cancer types were examined using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases, with key clinical characteristics (TNM and pathological stages, pathological grade, survival status) included. A nomogram model using MPP7 expressions and other clinical factors was built to predict the survival probability. The Kaplan-Meier plotter and Cox regression were employed to investigate the clinical significance and prognostic value of MPP7 in ccRCC. MPP7 expression-associated signaling pathways with were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) tools. The Tumor Immune Estimation Resource (TIMER) database was used to investigate the correlation between MPP7 and the infiltration patterns of immune cells. Results: By analyzing TCGA-kidney renal clear cell carcinoma (TCGA-KIRC) and HPA databases, we found that MPP7 was differentially expressed in tumor tissues and adjacent normal tissues (PMPP7 expression patterns were associated with pathological stage (PMPP7 expressions combined with key clinical factors could accurately predict the clinical prognosis. The promoter methylation patterns of MPP7 were correlated with the clinical factors of ccRCC patients. Furthermore, the KEGG and GO analyses demonstrated that MPP7 is associated with mitochondrial oxidative metabolism. MPP7 expression was associated with multiple types of immune cells and correlated with the enrichment of these cells. Conclusions: MPP7 is a critical gene links with ccRCC prognosis and is associated with tumor immune status and metabolism. MPP7 could become a potential biomarker and important therapeutic target for ccRCC patients.

This longitudinal cohort study explored the associations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), and β-C-terminal telopeptide of type 1 collagen (β-CTX) levels with all-cause mortality in centenarians. The study included 952 centenarians (81.4% female). During a median follow-up of 32 months, 752 (78.9%) centenarians died. The estimated 1-year, 3-year, and 5-year survival rates were 80.0%, 45.7%, and 23.6%, respectively. The association of mortality with 25(OH)D was linear, whereas the associations with PTH and β-CTX were J-shaped, with a lower risk below the median levels. Compared with 25(OH)D of ≥30 ng/mL, 25(OH)D < 30 ng/mL was associated with increased mortality (HR 1.52, 95% CI 1.24–1.86, p < 0.001). Compared with PTH of ≤65 pg/mL, PTH > 65 pg/mL was associated with increased mortality (HR 1.30, 95% CI 1.08–1.56, p = 0.005). Compared with β-CTX of p = 0.002). A higher β-CTX level (even in the clinical reference range of 0.55–1.01 ng/mL) was associated with increased mortality (HR 1.23, 95% CI 1.04–1.47, p = 0.018). Centenarians with 25(OH)D < 30 ng/mL, PTH > 65 pg/mL, and β-CTX ≥ 0.55 ng/mL had a 2.77-fold (95% CI 1.99–3.85, p < 0.001) increased risk of mortality when compared with those with 25(OH)D of >30 ng/mL, PTH < 65 pg/mL, and β-CTX < 0.55 ng/mL. Lower serum 25(OH)D and higher PTH and β-CTX were independently correlated with increased all-cause mortality in Chinese community-dwelling centenarians.