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Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Background: Human papillomavirus (HPV) infection is a worldwide reproductive system disease. Baofukang suppository, a traditional herbal preparation that includes curdione and borneol, has been reported to treat bacterial vaginosis (BV) and HPV infection in China. However, the therapeutic mechanism is still unknown. This study aims to explore the molecular mechanisms of curdione and borneol in treating HPV infection. Methods: We conducted a retrospective cohort analysis of medical records from a single-center study involving 205 HPV patients, focusing on the correlation between HPV clearance and co-infection with other pathogens, confirming the efficacy of Baofukang suppository. Bioinformatics and network pharmacology approaches were employed to identify therapeutic targets of Baofukang suppository for BV/HPV co-infections. qRT-PCR, Western blot, immunofluorescence staining, and flow cytometry were utilized to validate the therapeutic targets of curdione and borneol, along with the associated immune molecular changes. Finally, the molecular mechanisms and therapeutic efficacy of curdione and borneol were confirmed in vivo using an LPS/TC-1 cervical orthotopic injection model. Results: Curdione and borneol selectively inhibit the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) by macrophages. The reduction in IL-6 and IL-1β levels effectively inhibits the expression of CD274 (Programmed death ligand 1, PD-L1) in infected epithelial cells by inhibiting STAT3 phosphorylation, thereby suppressing their immune evasion capabilities. Furthermore, curdione and borneol enhance the expression of tumor necrosis factor α (TNF-α) and caspase 1 (CASP1) in macrophages, as well as the expression of interleukin 12 (IL-12) and interleukin 23 (IL-23) in dendritic cells (DCs). The expression of these inflammatory factors effectively promotes the migration and differentiation of T cells to the site of infection, completing the clearance of infected epithelial cells. Conclusion: The main components of Baofukang suppository, curdione and borneol, inhibit the progression of HPV infection and the occurrence of cervical cancer by modulating the communication between innate and adaptive immunity, promoting the recruitment and recognition of CD8+ T cells to eliminate HPV-infected epithelial cells. [ABSTRACT FROM AUTHOR]

In this study, two parallel lab-scale anaerobic membrane bioreactors (AnMBRs), one of which was dosed with polyaluminum chloride (PAC) for membrane fouling control, were operated for treating excess activated sludge collected from a wastewater treatment plant (WWTP). The AnMBRs were inoculated with anaerobic digested sludge collected from an anaerobic digester of another WWTP. The microbial community of digested sludge and cake layer in AnMBRs, as well as that of excess sludge, was analyzed through polymerase chain reaction coupled with denaturing gradient gel electrophoresis (PCR-DGGE) and Illumina MiSeq. The dynamic variation of archaeal community in AnMBRs was not as obvious as that of bacterial community based on the PCR-DGGE results. Under the circumstance of stable operation, Cloacimonetes, Chloroflexi, Bacteroidetes, Proteobacteria, Firmicutes, and Ignavibacteriae were observed as the predominant phyla in digested sludge based on the Illumina results. In addition to that, the cake layer possessed similar predominant phyla with the digested sludge but owned a higher diversity. Furthermore, overlapping bacterial communities were discovered between the excess sludge and digested sludge. However, the abundance of aerobic bacteria was substantially reduced, while the abundance of anaerobic microorganisms like phylum Cloacimonetes and Smithella was enriched in digested sludge over time. Additional PAC dosing, on the one hand, affected the bioavailable substrate, thus further changing the microbial community structure; on the other hand, aluminum itself also affected specific microbial communities. Besides, PAC dosing indirectly influenced the bacterial diversity in AnMBR as well. [ABSTRACT FROM AUTHOR]