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Alzheimer's disease (AD) is the most common type of progressive neurodegenerative disorder, and is responsible for the most common form of dementia in the elderly. Inflammation occurs in the brains of patients with AD, and is critical for disease progression. In the present study, the effects of rapamycin (RAPA) on neuroinflammation lipopolysaccharide (LPS)-induced were investigated. SH‑SY5Y human neuroblastoma cells were treated with 20 µg/ml LPS and 0.1, 1 or 10 nmol/l RAPA, and were analyzed at various time points (6, 12 and 24 h). The mRNA expression levels of interleukin (IL) 1β, IL6 and hypoxia‑inducible factor 1α (HIF1α) were determined using reverse transcription‑quantitative polymerase chain reaction. The protein expression levels of phosphorylated (p‑)S6, p‑nuclear factor κB (NFκB), p‑inhibitor of NFκB kinase subunit β (IKKβ) and p‑tau protein were measured by western blot analysis. p‑IKKβ, p‑NFκB, p‑S6 and p‑tau were significantly decreased at 6, 12 and 24 h when cells were treated with ≥0.1 nmol/ml RAPA. In addition, female Sprague Dawley rats were intracranially injected with a single dose of 100 µg/kg LPS in the absence or presence of 1 mg/kg RAPA pretreatment. Brain tissues were subjected to immunohistochemical analysis 6‑24 h later, which revealed that the expression levels of HIF1α and p‑S6 in rat cerebral cortex were increased following LPS injection; however, this increase was abrogated by RAPA treatment. RAPA may therefore be considered a potential therapeutic agent for the early or emergency treatment of neuroinflammation.

This paper mainly discussed the process to create finite element model of Y4-68 fan,and also analysis the nature frequency and liner static stress.According to the analysis result to determine the optimized parameters,to prepare for the stage of optimization.

Additional file 1. The effect of HS and DAPT on BV-2 cell viability.ppt. Panel A shows 40 mM HS, 60 mM HS, and 80 mM HS have no significant effect on BV-2 cell viability compared to OGD group (P > 0.05); but the BV-2 cell viability was significantly decreased in 100 mM HS (*P 0.05). The values represent the mean ± SD in triplicate. HS, hypertonic saline; DAPT, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycinet-butyl ester; OGD, oxygen glucose deprivation. ns, no significant difference.

This article summarized the general process of parametric modeling and finite element analysis of spur gear,PRO/E used to create parametric model,and Patran used to finite element analysis.Parametric modeling can reduce design period of the similar products,and modal analysis provide the basis for the selection and optimization of gear.

Finite element method(FEM) have been widely used in modern mechanical design,mesh generation is an important part of the finite element analysis,this article discussed the process of mesh generation through two practical cases and put forward some issues we should pay more attention to.

ntelligent transport system that based on Internet of Vehicles is regarded as effective measure to guarantee the safety of highway transport. Anti-worm model in vehicular IOT is constructed based on divide-and-conquer with velocity and the drive velocity of vehicle node as the conversion condition between active and passive anti-worms in hybrid anti-worms. Implement this model on the design of Internet of Vehicles terminal, the simulation results show that this model can make the performance of network improved in highway environment regardless of complex road conditions domain and provides a theoretical basis for programming real-time detection strategy and preventing worm destructive epidemics in vehicular Internet of things.

Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action.

Background Axon development plays a pivotal role in the formation of synapse, nodes of Ranvier, and myelin sheath. Interleukin-1β (IL-1β) produced by microglia may cause myelination disturbances through suppression of oligodendrocyte progenitor cell maturation in the septic neonatal rats. Here, we explored if a microglia-derived IL-1β would disturb axon development in the corpus callosum (CC) following lipopolysaccharide (LPS) administration, and if so, whether it is associated with disorder of synapse formation in the cerebral cortex and node of Ranvier. Methods Sprague-Dawley rats (1-day old) in the septic model group were intraperitoneally administrated with lipopolysaccharide (1 mg/kg) and then sacrificed for detection of IL-1β, interleukin-1 receptor (IL-1R1), neurofilament-68, neurofilament-160, and neurofilament-200, proteolipid, synaptophysin, and postsynaptic density 95 (PSD95) expression by western blotting and immunofluorescence. Electron microscopy was conducted to observe alterations of axonal myelin sheath and synapses in the cortex, and proteolipid expression was assessed using in situ hybridization. The effect of IL-1β on neurofilament and synaptophysin expression in primary neuron cultures was determined by western blotting and immunofluorescence. P38-MAPK signaling pathway was investigated to determine whether it was involved in the inhibition of IL-1β on neurofilament and synaptophysin expression. Results In 1-day old septic rats, IL-1β expression was increased in microglia coupled with upregulated expression of IL-1R1 on the axons. The expression of neurofilament-68, neurofilament-160, and neurofilament-200 (NFL, NFM, NFH) and proteolipid (PLP) was markedly reduced in the CC at 7, 14, and 28 days after LPS administration. Simultaneously, cortical synapses and mature oligodendrocytes were significantly reduced. By electron microscopy, some axons showed smaller diameter and thinner myelin sheath with damaged ultrastructure of node of Ranvier compared with the control rats. In the cerebral cortex of LPS-injected rats, some axo-dendritic synapses appeared abnormal looking as manifested by the presence of swollen and clumping of synaptic vesicles near the presynaptic membrane. In primary cultured neurons incubated with IL-1β, expression of NFL, NFM, and synaptophysin was significantly downregulated. Furthermore, p38-MAPK signaling pathway was implicated in disorder of axon development and synaptic deficit caused by IL-1β treatment. Conclusions The present results suggest that microglia-derived IL-1β might suppress axon development through activation of p38-MAPK signaling pathway that would contribute to formation disorder of cortical synapses and node of Ranvier following LPS exposure. Electronic supplementary material The online version of this article (doi:10.1186/s12974-017-0805-x) contains supplementary material, which is available to authorized users.