Polydimethylsiloxane(PDMS)-polystyrene(PS) interpenetrating polymer network(IPN) was prepared and characterized by FTIR, TGA, WCA, swelling experiments, and SEM. The IPN was used for pervaporation(PV) recovery of buta...Polydimethylsiloxane(PDMS)-polystyrene(PS) interpenetrating polymer network(IPN) was prepared and characterized by FTIR, TGA, WCA, swelling experiments, and SEM. The IPN was used for pervaporation(PV) recovery of butanol. Both the permeation flux and separation factor increased with feed temperature, and both water and butanol fluxes increased with feed concentration, while no obvious effect of concentration on separation factor was found. Through the formation of IPN structure, the total flux of PDMS-PS IPN pervaporation membrane increased greatly with the decrease of separation factor. At the feed temperature of 60 °C, the IPN membrane obtained a total flux of 920.3 g/m2h with a separation factor of 9.5.展开更多
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...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.展开更多
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei...Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.展开更多
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
Tourism has become the primary leisure activity for modern people,and a scenic spot’s appeal to tourists is closely linked to the quality of supporting catering services within the area.Improving satisfaction with ca...Tourism has become the primary leisure activity for modern people,and a scenic spot’s appeal to tourists is closely linked to the quality of supporting catering services within the area.Improving satisfaction with catering services in these scenic spots has become a key factor in promoting the development of urban tourist destinations.Using Zhangzhou,a tourist city,as an example,this paper conducts an empirical study on the satisfaction of catering services in Zhangzhou’s scenic spots through IPA analysis.Firstly,based on the scale of relevant influencing factors affecting catering service satisfaction in Zhangzhou’s scenic spots,a field questionnaire survey has been conducted.Three main levels,five core elements,and 31 sub-indicators have been summarized to construct the evaluation system for catering service satisfaction in scenic spots.Through the analysis of IPA data and the examination of various indicators related to catering services in Zhangzhou’s scenic spots,we analyze the influencing factors affecting tourists’satisfaction with catering services.Meanwhile,we also introduce the 4Ps demand theory of catering service.Finally,based on the analysis and evaluation of IPA quadrant and the 4Ps demand theory,we initially construct the 4Ps improvement path.This will provide theoretical and practical references for enhancing the catering service satisfaction of tourists in scenic spots.展开更多
Based on the Aki-Richards approximate equations for reflection coefficients and Bayes theorem, we developed an inversion method to estimate P- and S-wave velocity contrasts and density contrast from combined PP and PS...Based on the Aki-Richards approximate equations for reflection coefficients and Bayes theorem, we developed an inversion method to estimate P- and S-wave velocity contrasts and density contrast from combined PP and PS data. This method assumes that the parameters satisfy a normal distribution and introduces the covariance matrix to describe the degree of correlation between the parameters and thus to improve the inversion stability. Then, we suppose that the parameter sequence is subject to the Cauchy distribution and employs another matrix Q to describe the parameter sequence sparseness to improve the inversion result resolution. Tests on both synthetic and real multi-component data prove that this method is valid, efficient, more stable, and more accurate compared to methods using PP data only.展开更多
Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal funct...Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.展开更多
基金Funded by the National Natural Science Foundation of China(No.51572201)the National ‘Pilot Scheme for Advanced Students in Basic Studies’(No.20160210)the Wuhan University Experimental Center Open Experimental Project(No.WHU-2018-XYKF-10)
文摘Polydimethylsiloxane(PDMS)-polystyrene(PS) interpenetrating polymer network(IPN) was prepared and characterized by FTIR, TGA, WCA, swelling experiments, and SEM. The IPN was used for pervaporation(PV) recovery of butanol. Both the permeation flux and separation factor increased with feed temperature, and both water and butanol fluxes increased with feed concentration, while no obvious effect of concentration on separation factor was found. Through the formation of IPN structure, the total flux of PDMS-PS IPN pervaporation membrane increased greatly with the decrease of separation factor. At the feed temperature of 60 °C, the IPN membrane obtained a total flux of 920.3 g/m2h with a separation factor of 9.5.
基金supported by the National Natural Science Foundation of China,Nos.91849115 and U1904207(to YX),81974211 and 82171247(to CS)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2020-PT310-01(to YX).
文摘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.
基金financially supported by the National Natural Science Foundation of China,No.823 74552 (to WP)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220 (to WP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2020JJ4803 (to WP),2022JJ40723 (to MY)the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)
文摘Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.
基金supported by STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
基金Surpported by the National Social Science Foundation Western Project of China(19XJY010)。
文摘Tourism has become the primary leisure activity for modern people,and a scenic spot’s appeal to tourists is closely linked to the quality of supporting catering services within the area.Improving satisfaction with catering services in these scenic spots has become a key factor in promoting the development of urban tourist destinations.Using Zhangzhou,a tourist city,as an example,this paper conducts an empirical study on the satisfaction of catering services in Zhangzhou’s scenic spots through IPA analysis.Firstly,based on the scale of relevant influencing factors affecting catering service satisfaction in Zhangzhou’s scenic spots,a field questionnaire survey has been conducted.Three main levels,five core elements,and 31 sub-indicators have been summarized to construct the evaluation system for catering service satisfaction in scenic spots.Through the analysis of IPA data and the examination of various indicators related to catering services in Zhangzhou’s scenic spots,we analyze the influencing factors affecting tourists’satisfaction with catering services.Meanwhile,we also introduce the 4Ps demand theory of catering service.Finally,based on the analysis and evaluation of IPA quadrant and the 4Ps demand theory,we initially construct the 4Ps improvement path.This will provide theoretical and practical references for enhancing the catering service satisfaction of tourists in scenic spots.
基金supported by the China Important National Science & Technology Specific Projects (Grant No. 2011ZX05019-008)the National Natural Science Foundation of China (Grant No. 40839901)
文摘Based on the Aki-Richards approximate equations for reflection coefficients and Bayes theorem, we developed an inversion method to estimate P- and S-wave velocity contrasts and density contrast from combined PP and PS data. This method assumes that the parameters satisfy a normal distribution and introduces the covariance matrix to describe the degree of correlation between the parameters and thus to improve the inversion stability. Then, we suppose that the parameter sequence is subject to the Cauchy distribution and employs another matrix Q to describe the parameter sequence sparseness to improve the inversion result resolution. Tests on both synthetic and real multi-component data prove that this method is valid, efficient, more stable, and more accurate compared to methods using PP data only.
基金supported by the National Natural Science Foundation of China,No.82201582(to QT)Scientific and Technological Research Program of Chongqing Municipal Education Commission,No.KJQN202200457(to QT)+3 种基金General Project of Changqing Natural Science Foundation,No.cstc2021jcyjmsxmX0442(to ZL)CQMU Program for Youth Innovation in Future Medicine,No.W0044(to ZD and GH)Direct Research Project for PhD of Chongqing,No.CSTB2022BSXM-JCX0051(to ZL)the Project of the Top-Notch Talent Cultivation Program For the Graduate Students of Chongqing Medical University,No.BJRC202310(to CG)。
文摘Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.
