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.
The inventory management of multi-variety and small-batch material production is one of the important bases to maintain normal operation of manufacturing industry.This paper introduces a method of setting up the weekly forecast model of material demand to help enterprises make reasonable arrangement of material production.This model takes into account the comprehensive factors such as the predicted value of demand, the characteristics of demand, inventory and shortage quantity, so as to avoid the possible large inventory or shortage problem, improve the production efficiency and customer satisfaction, reduce the inventory cost, and bring economic benefits and competitive advantages for enterprises.
Graphene is a two-dimensional material with excellent performance and unique structure. Since its successful manufacturing in 2004, it has quickly become a research hotspot in the fields of materials, chemistry, physics, and engineering. This article focuses on the study of exfoliated single-layer graphene based on dispersed carbon nanotubes and understands the related theories of carbon nanotubes and exfoliated single-layer graphene on the basis of literature data. The mathematical model and simulation calculation method are analyzed, and then, the effect of the single-layer graphene peeling based on the dispersed carbon nanotubes is tested, mainly to the experimental verification of the peeling process parameters and the influence of the dispersant on the peeling effect, and then, the peeled graphite quality of the graphene was tested, and the test results showed that the thickness of single-layer pure graphene is 0.6-0.9 nm, and the experimental statistics show that the graphene of single-layer and double-layer occupies 81% of the experimental sample; most of the single-layer graphene exfoliated based on dispersed carbon nanotubes in this paper is single-layer, two-layer graphene, and a relatively small amount of multilayer graphene.
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