4,5-Bis(isopropyl­sulfan­yl)benzene-1,2-dicarbonitrile

In the title compound, C14H16N2S2, the C atoms of the aromatic ring, the two cyanide groups and the two S atoms of the isopropyl­sulfanyl groups are almost coplanar [maximum deviation from the mean plane = 0.042 (7) Å]. In the crystal, inversion dimers linked by aromatic π–π stacking occur, with a centroid–centroid separation of 3.7543 (8) Å

Serum uric acid to creatinine ratio as a risk factor for mortality among patients on continuous ambulatory peritoneal dialysis: a multi-center retrospective study

AbstractBackground Serum uric acid to serum creatinine ratio (SUA/Scr) has emerged as a new biomarker, which is significantly associated with several metabolic diseases. However, no study has investigated the association between SUA/Scr and mortality among patients on continuous ambulatory peritoneal dialysis (CAPD).Methods In this multicenter retrospective cohort study, we enrolled CAPD patients in eight tertiary hospitals in China from 1 January 2005 to 31 May 2021. Cox proportional hazard models were used to determine the relationship between SUA/Scr and mortality.Results A total of 2480 patients were included; the mean age was 48.9 ± 13.9 years and 56.2% were males. During 12648.0 person-years of follow-up, 527 (21.3%) patients died, of which 267 (50.7%) deaths were caused by cardiovascular disease. After multivariable adjustment for covariates, per unit increase in SUA/Scr was associated with a 62.9% (HR, 1.629 (95% confidence interval (CI) 1.420–1.867)) and 73.0% (HR, 1.730 (95% CI 1.467–2.041)) higher risk of all-cause and cardiovascular mortality. Results were similar when categorized individuals by SUA/Scr quartiles. Compared with the lowest quartile of SUA/Scr, the highest and the second highest quartile of SUA/Scr had a 2.361-fold (95% CI 1.810–3.080) and 1.325-fold (95% CI 1.003–1.749) higher risk of all-cause mortality, as well as a 3.701-fold (95% CI 2.496–5.489) and 2.074-fold (95% CI 1.387–3.100) higher risk of cardiovascular mortality. Multivariable-adjusted spline regression models showed nonlinear association of SUA/Scr with mortality in CAPD patients.Conclusions Higher levels of SUA/Scr were associated with higher risk of all-cause and cardiovascular mortality in CAPD patients

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Duck Tembusu virus (DTMUV) has recently appeared in ducks in China and the key cellular determiners for DTMUV replication in host cells remain unknown. Autophagy is an evolutionarily conserved cellular process that has been reported to facilitate flavivirus replication. In this study, we utilized primary duck embryo fibroblast (DEF) as the cell model and found that DTMUV infection triggered LC3-II increase and polyubiquitin-binding protein sequestosome 1 (p62) decrease, confirming that complete autophagy occurred in DEF cells. The induction of autophagy by pharmacological treatment increased DTMUV replication in DEF cells, whereas the inhibition of autophagy with pharmacological treatments or RNA interference decreased DTMUV replication. Inhibiting autophagy enhanced the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 7 (IRF7) pathways and increased the p62 protein level in DTMUV-infected cells. We further found that the overexpression of p62 decreased DTMUV replication and inhibited the activation of the NF-κB and IRF7 pathways, and changes in the NF-κB and IRF7 pathways were consistent with the level of phosphorylated TANK-binding kinase 1 (p-TBK1). Opposite results were found in p62 knockdown cells. In summary, we found that autophagy-mediated p62 degradation acted as a new strategy for DTMUV to evade host innate immunity

DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression

Duck tembusu virus (DTMUV) is a single-stranded, positive-polarity RNA flavivirus that has caused considerable economic losses in China in recent years. Innate immunity represents the first line of defense against invading pathogens and serves as an important role in resisting viral infections. In this study, we found that the infection of ducks by DTMUV triggers Toll-like receptors (TLRs) and (RIG-I)-like receptors (RLRs) signaling pathways and inducing abundant of pro-inflammatory factors and type I interferons (IFNs), in which melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 3 (TLR3) play important immunity roles, they can inhibit the replication process of DTMUV via inducing type I IFNs. Moreover, we demonstrated that type I IFNs can inhibit the DTMUV replication process in a time- and dose-dependent manner. Exosomes are small membrane vesicles that have important roles in intercellular communication. MicroRNAs (miRNAs) are small non-coding RNAs that can modulate gene expression and are common substances in exosomes. In our experiment, we successfully isolated DEF cells derived exosome for the first time and explored its function. Firstly, we found the expression of miR-148a-5p is significantly decreased following DTMUV infect. Then we found miR-148a-5p can target TLR3 and down-regulate the expression of TLR3, serving as a negative factor in innate immunity. Unfortunately, we cannot find miRNAs with different expression changes that can target MDA5. Lastly, our experimental results showed that TLR3 was one of the causes of miR-148a-5p reduction, suggesting that the high level of TLR3 after DTMUV infect can both trigger innate immunity and suppress miR-148a-5p to resist DTMUV