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Wang Chenfei,Lu Jia,Sha Xudong,Qiu Yu,Chen Hongzhuan,Yu Zhihua 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Although the ε4 allele of the apolipoprotein E (ApoE4) gene has been established as a genetic risk factor for many neurodegenerative diseases, including Alzheimer’s disease, the mechanism of action remains poorly understood. Transient receptor potential vanilloid 1 (TRPV1) was reported to regulate autophagy to protect against foam cell formation in atherosclerosis. Here, we show that ApoE4 leads to lipid metabolism dysregulation in microglia, resulting in enhanced MHC-II-dependent antigen presentation and T-cell activation. Lipid accumulation and inflammatory reactions were accelerated in microglia isolated from TRPV1flox/flox; Cx3cr1cre-ApoE4 mice. We showed that metabolic boosting by treatment with the TRPV1 agonist capsaicin rescued lipid metabolic impairments in ApoE4 neurons and defects in autophagy caused by disruption of the AKT-mTOR pathway. TRPV1 activation with capsaicin reversed ApoE4-induced microglial immune dysfunction and neuronal autophagy impairment. Capsaicin rescued memory impairment, tau pathology, and neuronal autophagy in ApoE4 mice. Activation of TRPV1 decreased microglial phagocytosis of synapses in ApoE4 mice. TRPV1 gene deficiency exacerbated recognition memory impairment and tau pathology in ApoE4 mice. Our study suggests that TRPV1 regulation of lipid metabolism could be a therapeutic approach to alleviate the consequences of the ApoE4 allele.
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Effect of Ball Endc Cutterc Tilt Milling on Path Interval of Blade Surface
Jiaheng Ma,Fujian Ma,Ziguang Wang,Zhihua Sha,Shengfang Zhang 한국정밀공학회 2022 International Journal of Precision Engineering and Vol.23 No.10
Different milling posture of ball-end cutter will alter path interval and affect surface scallop-height, which was an important problem to be considered to enhance the quality and efficiency of blade surface. In view of ball end cutter tilt milling of blade surface, the relation equation between path interval and scallop-height was established by constant scallop-height method, based on the determination of collision boundary and milling sensitivity, the optimal tilt angles and path interval of blade surface milling were solved, moreover, by means of cutting simulation method, the differences between tilt milling and traditional non-tilt milling were compared and analyzed from the perspective of scallop height and processing time, and verified through comparative experiments. The results show that the optimal tilt angles of blade surface milling is 36.9°, when the path interval is fixed, the surface roughness of non-tilt milling and tilt milling are 0.719 µm and 0.561 µm respectively, the surface processing quality of tilt milling is 28.2% higher than that of non-tilt milling, when scallop-height is fixed, the total time of non-tilt milling and tilt milling are 31.21 min and 25.46 min respectively, the machining efficiency of tilt milling is 17.1% higher than that of non-tilt milling. The effectiveness of tilt milling method is verified, which can provide reference basis for high-quality and efficient machining of similar blade surfaces.
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