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
To comprehensively assess the current state-of-art in asphalt foaming technology, the following four key aspectshave been reviewed systematically: foaming principles, test methods, evaluation indicators, and influenci...To comprehensively assess the current state-of-art in asphalt foaming technology, the following four key aspectshave been reviewed systematically: foaming principles, test methods, evaluation indicators, and influencing factors.Key findings reveal that asphalt foaming was primarily driven by the vaporization of water, with deteriorationprocesses including bubble collapse and liquid film drainage. However, the current understanding of asphaltfoaming principles remains limited, primarily due to difficulties in capturing and precisely measuring its microscopic behaviors during asphalt foaming process. Volume changes provided an intuitive means to evaluate theexpansion capacity of asphalt and its foaming stability. Bubble evolution characteristics of foamed asphalt offeredpromising insights into its foaming performance. Traditional ruler and stopwatch-based assessments were beingsuperseded by automated techniques like laser and ultrasonic ranging. Nevertheless, the current measuringequipment still lacks the capability to comprehensively evaluate the foaming effect of asphalt across various dimensions. Asphalt temperature and foaming water consumption significantly affected asphalt foaming performance, and the inclusion of foaming agents typically led to a notable increase in the half life of foamed asphalt.However, the interaction between foaming agents and asphalt, as well as the underlying mechanisms affecting thefoaming effect, are still unclear and require further exploration. Future research should primarily focus on thecorrelation between asphalt foaming effect and mixture performance, aiming to guide the practical engineeringapplication of foamed asphalt mixtures and enlarge the advantages of such low-emission and sustainable mixtures.展开更多
BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood ...BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood UL16-binding protein 2(ULBP2)and human fibrinogen degradation products(DR-70)are the main indicators for the diagnosis of malignant tumors.AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODS This study involved 60 patients with early-stage CRC(CRC group),50 patients with benign colorectal tumors(benign group),and 50 healthy patients(control group)enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January,2020 and January,2022.ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined.Patients with CRC were divided into the good prognosis and poor prognosis groups,and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups(P<0.05);however,no significant differences were observed between the benign and control groups(P>0.05).Among the 60 patients with CRC followed up for two years,two died(3.33%)and 15 exhibited tumor metastasis,progression,or recurrence(25.00%).ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group(P<0.05).A receiver operating characteristic curve was plotted.Area under the curve,sensitivity,and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices(P<0.05)in both the good and poor prognosis groups.CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC.They improved the diagnostic rate of early-stage CRC and predicted patient prognosis,thereby showing clinical application potential.展开更多
Determination of Shear Bond strength(SBS)at interlayer of double-layer asphalt concrete is crucial in flexible pavement structures.The study used three Machine Learning(ML)models,including K-Nearest Neighbors(KNN),Ext...Determination of Shear Bond strength(SBS)at interlayer of double-layer asphalt concrete is crucial in flexible pavement structures.The study used three Machine Learning(ML)models,including K-Nearest Neighbors(KNN),Extra Trees(ET),and Light Gradient Boosting Machine(LGBM),to predict SBS based on easily determinable input parameters.Also,the Grid Search technique was employed for hyper-parameter tuning of the ML models,and cross-validation and learning curve analysis were used for training the models.The models were built on a database of 240 experimental results and three input variables:temperature,normal pressure,and tack coat rate.Model validation was performed using three statistical criteria:the coefficient of determination(R2),the Root Mean Square Error(RMSE),and the mean absolute error(MAE).Additionally,SHAP analysis was also used to validate the importance of the input variables in the prediction of the SBS.Results show that these models accurately predict SBS,with LGBM providing outstanding performance.SHAP(Shapley Additive explanation)analysis for LGBM indicates that temperature is the most influential factor on SBS.Consequently,the proposed ML models can quickly and accurately predict SBS between two layers of asphalt concrete,serving practical applications in flexible pavement structure design.展开更多
A molecular dynamics simulation study was performed to investigate the formation and evolution mechanisms of nano-clusters during the rapid solidification of liquid CaToMg30 alloy. The cluster-type index method （CTIM...A molecular dynamics simulation study was performed to investigate the formation and evolution mechanisms of nano-clusters during the rapid solidification of liquid CaToMg30 alloy. The cluster-type index method （CTIM） was adopted to describe microstructure evolutions of nano-clusters during solidification. Results indicate that amorphous structure is mainly formed with three bond-types of 1551, 1541 and 1431 at the cooling rate of 5~1011 K/S, and glass transition temperature Tg is about 530 K; the icosahedron cluster of （12 0 12 0） plays a key role in formation of amorphous structure, and smaller Mg atoms are much more probable to be central atoms of icosahedron clusters; and nano-clusters are mainly formed by combining medium-size clusters. Interestingly, it was also found that formation and evolution processes of the nano-cluster display a three-stage feature which is analogous to crystallization process of amorphous alloy.展开更多
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the National Natural Science Foundation of China(Grant No.52378452)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_1193)+1 种基金Nanjing Transportation Science and Technology Project(JSZC-320100-HBGLC2023-0037)Nantong Highway Development Center Science and Technology Project(2022PMLQYJ)and 333 High-level Talent Project of Jiangsu Province(6th).
文摘To comprehensively assess the current state-of-art in asphalt foaming technology, the following four key aspectshave been reviewed systematically: foaming principles, test methods, evaluation indicators, and influencing factors.Key findings reveal that asphalt foaming was primarily driven by the vaporization of water, with deteriorationprocesses including bubble collapse and liquid film drainage. However, the current understanding of asphaltfoaming principles remains limited, primarily due to difficulties in capturing and precisely measuring its microscopic behaviors during asphalt foaming process. Volume changes provided an intuitive means to evaluate theexpansion capacity of asphalt and its foaming stability. Bubble evolution characteristics of foamed asphalt offeredpromising insights into its foaming performance. Traditional ruler and stopwatch-based assessments were beingsuperseded by automated techniques like laser and ultrasonic ranging. Nevertheless, the current measuringequipment still lacks the capability to comprehensively evaluate the foaming effect of asphalt across various dimensions. Asphalt temperature and foaming water consumption significantly affected asphalt foaming performance, and the inclusion of foaming agents typically led to a notable increase in the half life of foamed asphalt.However, the interaction between foaming agents and asphalt, as well as the underlying mechanisms affecting thefoaming effect, are still unclear and require further exploration. Future research should primarily focus on thecorrelation between asphalt foaming effect and mixture performance, aiming to guide the practical engineeringapplication of foamed asphalt mixtures and enlarge the advantages of such low-emission and sustainable mixtures.
文摘BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood UL16-binding protein 2(ULBP2)and human fibrinogen degradation products(DR-70)are the main indicators for the diagnosis of malignant tumors.AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODS This study involved 60 patients with early-stage CRC(CRC group),50 patients with benign colorectal tumors(benign group),and 50 healthy patients(control group)enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January,2020 and January,2022.ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined.Patients with CRC were divided into the good prognosis and poor prognosis groups,and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups(P<0.05);however,no significant differences were observed between the benign and control groups(P>0.05).Among the 60 patients with CRC followed up for two years,two died(3.33%)and 15 exhibited tumor metastasis,progression,or recurrence(25.00%).ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group(P<0.05).A receiver operating characteristic curve was plotted.Area under the curve,sensitivity,and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices(P<0.05)in both the good and poor prognosis groups.CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC.They improved the diagnostic rate of early-stage CRC and predicted patient prognosis,thereby showing clinical application potential.
基金the University of Transport Technology under grant number DTTD2022-12.
文摘Determination of Shear Bond strength(SBS)at interlayer of double-layer asphalt concrete is crucial in flexible pavement structures.The study used three Machine Learning(ML)models,including K-Nearest Neighbors(KNN),Extra Trees(ET),and Light Gradient Boosting Machine(LGBM),to predict SBS based on easily determinable input parameters.Also,the Grid Search technique was employed for hyper-parameter tuning of the ML models,and cross-validation and learning curve analysis were used for training the models.The models were built on a database of 240 experimental results and three input variables:temperature,normal pressure,and tack coat rate.Model validation was performed using three statistical criteria:the coefficient of determination(R2),the Root Mean Square Error(RMSE),and the mean absolute error(MAE).Additionally,SHAP analysis was also used to validate the importance of the input variables in the prediction of the SBS.Results show that these models accurately predict SBS,with LGBM providing outstanding performance.SHAP(Shapley Additive explanation)analysis for LGBM indicates that temperature is the most influential factor on SBS.Consequently,the proposed ML models can quickly and accurately predict SBS between two layers of asphalt concrete,serving practical applications in flexible pavement structure design.
基金Project(50831003) supported by the National Natural Science Foundation of ChinaProject(20114BAB215026) supported by Jiangxi Provincial Natural Science Foundation,ChinaProject(ZD201002) supported by Fund for Basic Scientific Research of Gannan Medical University,China
文摘A molecular dynamics simulation study was performed to investigate the formation and evolution mechanisms of nano-clusters during the rapid solidification of liquid CaToMg30 alloy. The cluster-type index method （CTIM） was adopted to describe microstructure evolutions of nano-clusters during solidification. Results indicate that amorphous structure is mainly formed with three bond-types of 1551, 1541 and 1431 at the cooling rate of 5~1011 K/S, and glass transition temperature Tg is about 530 K; the icosahedron cluster of （12 0 12 0） plays a key role in formation of amorphous structure, and smaller Mg atoms are much more probable to be central atoms of icosahedron clusters; and nano-clusters are mainly formed by combining medium-size clusters. Interestingly, it was also found that formation and evolution processes of the nano-cluster display a three-stage feature which is analogous to crystallization process of amorphous alloy.
