AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Improving schedule adherence based on dynamic signal control and speed guidance in connected bus system

Purpose–The purpose of this paper is to develop a dynamic control method to improve bus schedule adherence under connected bus system.Design/methodology/approach–The authors developed a dynamic programming model that optimally schedules the bus operating speed at road sections and multiple signal timing plans at intersections to improve bus schedule adherence.First,the bus route was partitioned into three types of sections:stop,road and intersection.Then,transit agencies can control buses in real time based on all collected information;i.e.control bus operating speed on road sections and adjust the signal timing plans through signal controllers to improve the schedule adherence in connected bus environment.Finally,bus punctuality at the downstream stop and the saturation degree deviations of intersections were selected as the evaluation criteria in optimizing signal control plans and bus speeds jointly.Findings–An illustrative case study by using a bus rapid transit line in Jinan city was performed to verify the proposed model.It revealed that based on the proposed strategy,the objective value could be reduced by 73.7%,which indicated that the punctuality was highly improved but not to incur excessive congestion for other vehicular traffic.Originality/value–In this paper,the authors applied speed guidance and the adjustment of the signal control plans for multiple cycles in advance to improve the scheduled stability;furthermore,the proposed control strategy can reduce the effect on private traffics to the utmost extend.