BackgroundWe investigated whether the effect of air pollution on daily mortality is enhanced by high temperatures in Wuhan, China, using data from 2001 to 2004. Wuhan has been called an “oven” city because of its hot summers. Approximately 4.5 million permanent residents live in the 201-km2 core area of the city.MethodWe used a generalized additive model to analyze pollution, mortality, and covariate data. The estimates of the interaction between high temperature and air pollution were obtained from the main effects and pollutant–temperature interaction models.ResultsWe observed effects of consistently and statistically significant interactions between particulate matter ≤ 10 μm (PM10) and temperature on daily nonaccidental (p = 0.014), cardiovascular (p = 0.007), and cardiopulmonary (p = 0.014) mortality. The PM10 effects were strongest on extremely high-temperature days (daily average temperature, 33.1°C), less strong on extremely low-temperature days (2.2°C), and weakest on normal-temperature days (18.0°C). The estimates of the mean percentage of change in daily mortality per 10-μg/m3 increase in PM10 concentrations at the average of lags 0 and 1 day during hot temperature were 2.20% (95% confidence interval), 0.74–3.68) for nonaccidental, 3.28% (1.24–5.37) for cardiovascular, 2.35% (−0.03 to 4.78) for stroke, 3.31% (−0.22 to 6.97) for cardiac, 1.15% (−3.54% to 6.07) for respiratory, and 3.02% (1.03–5.04) for cardiopulmonary mortality.ConclusionsWe found synergistic effects of PM10 and high temperatures on daily nonaccidental, cardiovascular, and cardiopulmonary mortality in Wuhan.

Osteoarthritis (OA) is a serious disease of the articular cartilage, and inflammation has been implicated in its pathogenesis. Previously, microRNAs (miRNAs) have been proposed as novel regulators of inflammation, however, the functional role of microRNAs in regulating inflammation in OA remains to be fully elucidated. The aim of the present study was to investigate the roles of miRNAs in OA inflammation and the underlying molecular mechanism. Firstly, the miRNA expression patterns were analyzed in the articular cartilage tissues from experimental OA mice using an miRNA microarray. miRNA (miR)-93 was identified with particular interest due to its reported effects on apoptosis and inflammation suppression. Subsequently, the expression of miR-93 was further validated in the articular cartilage tissues of OA mice and lipopolysaccharide (LPS)-stimulated primary chondrocytes. Using this LPS-induced chondrocyte injury model, the overexpression of miR-93 enhanced cell viability, improved cell apoptosis and attenuated the inflammatory response, as reflected by reductions in pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. In addition, Toll-like receptor 4 (TLR4), an important regulator of the nuclear factor-κB (NF-κB) signaling pathway, was identified as a direct target of miR-93 in chondrocytes. Furthermore, the restoration of TLR4 markedly abrogated the inhibitory effects of miR-93 on the chondrocyte apoptosis and inflammation induced by LPS. In addition, the overexpression of miR-93 by agomir-miR-93 significantly inhibited the levels of pro-inflammatory cytokines and cell apoptosis, whereas antagomir-93 exacerbated apoptosis and inflammation in vivo. Taken together, the results of the study suggested that miR-93 may be a promising therapeutic target for the treatment of human OA.

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Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, catalyzes the formation of the second messenger 2′3′-cGAMP that binds to STING and triggers the type I IFN signaling. Activation of cGAS can be modulated by several protein posttranslational modifications, including ubiquitination. However, the cGAS activation regulated by protein deubiquitination remains poorly understood. In this study, we identified that deubiquitinase USP27X could interact with cGAS and cleave K48-linked polyubiquitination chains from cGAS, leading to cGAS stabilization. Consistently, knockout of Usp27x in mice macrophages resulted in an accelerated turnover of cGAS, decreased cGAMP production, phosphorylation of TBK1 and IRF3, and IFN-β production. Furthermore, Usp27x knockout mice macrophages showed impaired innate antiviral responses against HSV type 1 infection. Our data suggest that USP27X is a novel regulator of the cGAS–STING cytosolic DNA sensing pathway.

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Progranulin (PGRN) plays an important role in Alzheimer's disease (AD) through participating in altering neurite outgrowth and neuronal survival. Previous studies identified that rs5848 in the 3'-untranslated region (3'-UTR) of the PGRN gene (GRN) is strongly associated with AD in Caucasians. In order to assess the involvement of the GRN polymorphism in the risk of late-onset AD (LOAD), we analyzed the genotype and allele distributions of rs5848 in 2350 Han Chinese subjects (AD, 992; control, 1358). The minor T allele of rs5848 was significantly associated with an increased risk of LOAD (P = 0.005, odds ratio (OR) = 1.197, 95 % confidence interval (CI) = 1.057-1.355). Moreover, the association was further validated in the multivariate logistic regression analysis (dominant model: OR = 1.195, P = 0.038, recessive model: OR = 1.386, P = 0.025; additive model: OR = 1.187, P = 0.009). Interestingly, we observed that the interaction between apolipoprotein E (APOE) and rs5848 significantly altered the risk for AD. The rs5848 polymorphism was only significantly associated with LOAD in APOE ε4 allele carriers. Then we included five studies (including the present study) and conducted a meta-analysis which consisted of 3236 cases (male, 1152; female, 2084) and 3405 (male, 1436; female, 1969) controls. The result of the meta-analysis supported T allele of rs5848 within GRN as a risk factor for AD. In conclusion, our results demonstrated that rs5848 polymorphism within GRN was associated with LOAD.