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Previous studies have shown that the ATP-P2X4 receptor signaling pathway mediates the activation of the Nod-like receptor family protein 3 (NLRP3) inflammasome. The NLRP3 inflammasome may promote renal interstitial inflammation in diabetic nephropathy. As inflammation also plays an important role in the pathogenesis of Parkinson's disease, we hypothesized that the ATP-P2X4 receptor signaling pathway may activate the NLRP3 inflammasome in Parkinson's disease. A male rat model of Parkinson's disease was induced by stereotactic injection of 6-hydroxydopamine into the pars compacta of the substantia nigra. The P2X4 receptor and the NLRP3 inflammasome (interleukin-1β and interleukin-18) were activated. Intracerebroventricular injection of the selective P2X4 receptor antagonist 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) or knockdown of P2X4 receptor expression by siRNA inhibited the activation of the NLRP3 inflammasome and alleviated dopaminergic neurodegeneration and neuroinflammation. Our results suggest that the ATP-P2X4 receptor signaling pathway mediates NLRP3 inflammasome activation, dopaminergic neurodegeneration, and dopamine levels. These findings reveal a novel role of the ATP-P2X4 axis in the molecular mechanisms underlying Parkinson's disease, thus providing a new target for treatment. This study was approved by the Animal Ethics Committee of Qingdao University, China, on March 5, 2015 (approval No. QYFYWZLL 26119).

Many studies have researched the mitochondrial DNA (mtDNA) A10398G in Parkinson's disease (PD) to determine the association between mtDNA A10398G and PD, but the results of their research were not consistent. Therefore, we performed a meta-analysis to demonstrate the connection between mtDNA A10398G and the susceptibility of PD. We searched PubMed, Web of Science, Springer Link, EMBASE and EBSCO databases up to identify relevant studies. Through strict inclusion and exclusion criteria, at last, 9 studies (total 3381 cases and 2810 controls) were included in our meta-analysis. We used the STATA 12.0 statistics software to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the genetic association between mtDNA A10398G and the risk of PD. We performed subgroup analysis to clarify the possible roles of the mtDNA A10398G polymorphism in the aetiology of PD in different ethnicities. Our meta-analysis indicates that although there was no significant association between mtDNA A10398G and PD in the Asian population (G vs. A: OR = 1.090, 95% CI = 0.939-1.284, P = 0.242), in the Caucasian population the G allele of mtDNA A10398G mutations may be a potential protective factor of PD (G vs. A: OR = 0.699, 95% CI = 0.546-0.895, P = 0.005). Further well-designed studies with larger samples are needed to validate these results.

In order to accurately describe the uncertainty in production environment, an approach on making production planning with fuzzy information is proposed. Based on the credibility theory, a fuzzy chance-constrained programming model is established. With the uncertain information presented as trapezoidal fuzzy number, the model can be transformed into its corresponding crisp equivalent model. In the end, the proposed approach is applied to a realistic fuzzy APP problem, and the result demonstrates that production planning can be modeled into a fuzzy chance-constrained programming and the model can well describe the uncertainty in actual environment.