Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
According to the detailed balanced limit for a singlejunction solar cell, tin−lead (Sn−Pb) perovskite solar cells (PSCs) can achieve power conversion efficiencies (PCEs) more than Pb-PSCs. However, the rise in PCE of Sn−Pb PSCs is limited by the choice of hole transport layer to PEDOT:PSS only. Inspired by the use of hole selective monolayers (HSM) in Pb only PSCs, here, we employed 2-(9H-carbazol-9-yl) ethyl] phosphonic acid (2PACz), leading to PCE (21.39%) comparable to PSCs fabricated on conventional PEDOT:PSS (21.37%). Moreover, we reported a small molecule, methyl phosphonic acid (MPA), employing which an equipotential performance (PCE= 21.08%) was obtained owing to its passivation effect on the transparent conducting oxide (TCO) layer. Furthermore, by taking motivation from the idea of cosensitization in dye sensitized solar cells, we explored the point that the coabsorption of 2-(9H-carbazol-9-yl) ethyl] phosphonic acid (2PACz) and a small molecule MPA on TCO glass led to the Sn−Pb PSC (1.25 eV) with a PCE of 23.3% and open-circuit voltage of 0.88 V.
Aim:Oxidative stress (OS) biomarkers have been detected in saliva and gingival crevicular fluid (GCF) during chronic periodontitis (CP) progression; however, the relationship between OS biomarkers and CP progression remains elusive. The purpose of this meta-analysis is to investigate the relationship between local OS biomarkers and CP.Methods: This review was conducted through a systematic search from three databases. Studies on CP participants were included as an experimental group, and studies on periodontally healthy (PH) participants were included as a control. Mean effects were expressed as standardized mean difference with their associated 95% confidence intervals.Results: From a total of 2,972 articles, 32 articles fulfilled the inclusion criteria. We found a significant decrease of total antioxidant capacity and a significant increase of malondialdehyde (MDA), nitric oxide, total oxidant status (TOS), and 8-hydroxy-deoxyguanosine levels in the saliva of CP patients. Moreover, we also found an elevation of MDA level in GCF of CP group when compared with the PH group. There were no significant differences of salivary and GCF superoxide dismutase levels, salivary glutathione peroxidase level, and GCF TOS level between two groups. However, a high heterogeneity was observed among evaluated studies. Conclusions:Despite the limitations of this study, the result of our meta-analysis supported the rationale that there was a direct link between CP and OS-related biomarkers' levels in the local site, indicating the important role of OS in the onset and development of CP. K E Y W O R D S biomarker, chronic periodontitis, gingival crevicular fluid, oxidative stress, saliva | 609 CHEN Et al.
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