Small extracellular vesicles (sEVs) participate in the pathological progression of high glucose (HG)-induced kidney injury, which is closely related to diabetic nephropathy. How sEVs specifically mediate the cell biom...Small extracellular vesicles (sEVs) participate in the pathological progression of high glucose (HG)-induced kidney injury, which is closely related to diabetic nephropathy. How sEVs specifically mediate the cell biomechanics underlying HG injury is unclear. Herein, we utilized a versatile atomic force microscope to determine the contributions of sEVs in HG-induced cellular injury. The sEVs extracted from the culture medium of human proximal tubule kidney (HK-2) cells treated by HG for 72 h (HG-induced sEVs) were verified and analyzed by multiple techniques, and the results indicated the effective production and the effect of dehydration on the shape of HG-induced sEVs. Further investigation on the morphologies of HK-2 cells treated by HG-induced sEVs showed that the surface roughness of the HK-2 cells increased, and their pseudopodia transitioned from lamellipodia to filopodia, with almost doubled mean pseudopodia length. Quantitative analysis of the mechanical responses of the cells revealed that the mean Young’s modulus increased by 26.2%, and the mean adhesion decreased by 36.8%. The indirect mediation of cellular biomechanics guided by HG-induced sEVs was evaluated by comparing it with previously studied direct HG injury. The HG-induced sEVs caused a greater reduction in cell adhesion and an increase in Young’s modulus compared with direct HG stimulation. This work suggested the ability of HG-induced sEVs to elicit specific biomechanical responses during HG injury, advancing the understanding of the injury mechanism caused by HG. The comparison of the cellular biomechanics between direct and indirect HG stimulations through HG-induced sEVs can be beneficial for the diagnosis and treatment of kidney injury.展开更多
Gigacycle fatigue behavior of 60Si2CrVA high strength spring steel was investigated by ultrasonic fatigue test machine. Fatigue fractography was observed by scanning electron microscopy （SEM）. Maximum inclusion size...Gigacycle fatigue behavior of 60Si2CrVA high strength spring steel was investigated by ultrasonic fatigue test machine. Fatigue fractography was observed by scanning electron microscopy （SEM）. Maximum inclusion sizes and fatigue strength in different volumes were estimated by statistics of extreme values （SEV） and generalized Pareto distribution （GPD） methods. The results showed that S N curves of 60Si2CrVA spring steels for two rolling processes were not horizontal asymptotes but a gradient in a regime of 109 cycles, and traditional fatigue limits were eliminated. Surface machined topography and inclusions in steel were major factors that led to elimination of fatigue limit for 60Si2CrVA spring steel. The SEV and GPD methods could effectively predict size of the maximum inclusion and fatigue strength in different volumes of 60Si2CrVA spring steel. Predicted fatigue strength was in accordance with experimental results by ultrasonic fatigue testing.展开更多
Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like prote...Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.展开更多
Laayoune and the Foum El Oued aquifers are in hydraulic communication only at the level of Oued Saguia El Hamra. The present study has accordingly made use of all the hydrogeological, hydrological, geological and geop...Laayoune and the Foum El Oued aquifers are in hydraulic communication only at the level of Oued Saguia El Hamra. The present study has accordingly made use of all the hydrogeological, hydrological, geological and geophysical data that preceded the watershed of Oued Saguia El Hamra in its downstream part. These data are by no means omplementary with the objective of having a better understanding of the boundary line between Laayoune and Foum El Oued aquifers and the origin of feeding the sources of Oued Saguia El Hamra. This study will focus only on the previous geophysical studies where a reinterpretation of electrical soundings has proved useful as a result of the recent well-logging results. It makes it possible to highlight the presence of a significant rise in the truncated marly substratum of Oued Saguia El Hamra and depressions (left and right banks) which could correspond to stream channels or depressed areas. At the level of the Wadi bed, there has been a regular immersion of the conductive level roofs from east to west towards Foum El Oued favoring the flow of wastewater from the zone and spraying the brackish water sources towards the groundwater of Foum El Oued. In the light of the reinterpretation of electric polls, plus as well as the geophysical surveys by electrical tomography and high definition made at the right and left banks of the Oueed Saguia El-Hamra, it was possible to verify the existence of dry ridge separating the two webs of Laayoune and Foum El Oued and stream channels or depressed areas of the left bank for drainage of brackish water to sources located along Oued Saguia El Hamra. The true resistivity models tomography profiles confirm the presence of the backbone at the left and right banks and the graben of the left bank for underground water drainage of the web Laayoune to sources welling the river Saguia El Hamra. They reveal the presence of a quaternary plio-cover (coastal platform Moghrebian) as being heterogeneous and affected by many electrical discontinuities, particularly in the level resistant R2 (coquina sandstone). These discontinuities could correspond to lateral changes in facies and/or synsedimental faults compartmentalizing the plio-quaternary formations into a system of Horsts and Grabens that relies on the whole (D1, Cs) attributed to formations from the Miocene to the Upper Cretaceous. The contours of the map show the distribution of the three families of electrical soundings A, B and C limited by two main electrical discontinuities D and M. East of discontinuity million, this map reflects the look of the wall of the Pliocene-Quaternary resting on the impermeable upper Cretaceous floor. To the west of this electrical discontinuity M, the map reflects the behavior of the roof of marl deposits of Miocene age.展开更多
The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracell...The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracellular vesicles(sEVs)derived from mesenchymal stem cells hold great potential in tissue repair.Nevertheless,the poor homing and retention of sEVs greatly limited their possible clinical application.In the present work,DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs(CREKA-sEVs),which could target fibrin to accumulate and retain in bone defects.Our results showed that CREKA-sEVs,like sEVs,promoted the osteogenic differentiation of BMSCs,the angiogenic property of HUVECs,and modulated the polarization of macrophages in vitro.Furthermore,due to the improved fibrin-binding and retention capacity of CREKA-sEVs,they enhanced the bone repair substantially in the rat femoral defect model.This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.展开更多
This paper presents a comprehensive survey on the development of Intel SGX(software guard extensions)processors and its applications.With the advent of SGX in 2013 and its subsequent development,the corresponding rese...This paper presents a comprehensive survey on the development of Intel SGX(software guard extensions)processors and its applications.With the advent of SGX in 2013 and its subsequent development,the corresponding research works are also increasing rapidly.In order to get a more comprehensive literature review related to SGX,we have made a systematic analysis of the related papers in this area.We first search through five large-scale paper retrieval libraries by keywords(i.e.,ACM Digital Library,IEEE/IET Electronic Library,SpringerLink,Web of Science,and Elsevier Science Direct).We read and analyze a total of 128 SGX-related papers.The first round of extensive study is conducted to classify them.The second round of intensive study is carried out to complete a comprehensive analysis of the paper from various aspects.We start with the working environment of SGX and make a conclusive summary of trusted execution environment(TEE).We then focus on the applications of SGX.We also review and study multifarious attack methods to SGX framework and some recent security improvements made on SGX.Finally,we summarize the advantages and disadvantages of SGX with some future research opportunities.We hope this review could help the existing and future research works on SGX and its application for both developers and users.展开更多
基金supported by National Natural Science Foundation Program of China(No.62175020)EU H2020 Program(ENSIGN No.101086226)+2 种基金Jilin Provincial Science and Technology Program(Nos.20210101038JC,2020C022-1,20190201287JC and 20190702002GH),Jilin Provincial Education Department(JJKH20220781KJ)“111”Project of China(D17017)This work was also partly supported by Changli Nano Biotechnology(China)and China Scholarship Council(CSC,No.202007585007).
文摘Small extracellular vesicles (sEVs) participate in the pathological progression of high glucose (HG)-induced kidney injury, which is closely related to diabetic nephropathy. How sEVs specifically mediate the cell biomechanics underlying HG injury is unclear. Herein, we utilized a versatile atomic force microscope to determine the contributions of sEVs in HG-induced cellular injury. The sEVs extracted from the culture medium of human proximal tubule kidney (HK-2) cells treated by HG for 72 h (HG-induced sEVs) were verified and analyzed by multiple techniques, and the results indicated the effective production and the effect of dehydration on the shape of HG-induced sEVs. Further investigation on the morphologies of HK-2 cells treated by HG-induced sEVs showed that the surface roughness of the HK-2 cells increased, and their pseudopodia transitioned from lamellipodia to filopodia, with almost doubled mean pseudopodia length. Quantitative analysis of the mechanical responses of the cells revealed that the mean Young’s modulus increased by 26.2%, and the mean adhesion decreased by 36.8%. The indirect mediation of cellular biomechanics guided by HG-induced sEVs was evaluated by comparing it with previously studied direct HG injury. The HG-induced sEVs caused a greater reduction in cell adhesion and an increase in Young’s modulus compared with direct HG stimulation. This work suggested the ability of HG-induced sEVs to elicit specific biomechanical responses during HG injury, advancing the understanding of the injury mechanism caused by HG. The comparison of the cellular biomechanics between direct and indirect HG stimulations through HG-induced sEVs can be beneficial for the diagnosis and treatment of kidney injury.
基金Sponsored by National Basic Research Program(973 Program)of China(2004CB619100)
文摘Gigacycle fatigue behavior of 60Si2CrVA high strength spring steel was investigated by ultrasonic fatigue test machine. Fatigue fractography was observed by scanning electron microscopy （SEM）. Maximum inclusion sizes and fatigue strength in different volumes were estimated by statistics of extreme values （SEV） and generalized Pareto distribution （GPD） methods. The results showed that S N curves of 60Si2CrVA spring steels for two rolling processes were not horizontal asymptotes but a gradient in a regime of 109 cycles, and traditional fatigue limits were eliminated. Surface machined topography and inclusions in steel were major factors that led to elimination of fatigue limit for 60Si2CrVA spring steel. The SEV and GPD methods could effectively predict size of the maximum inclusion and fatigue strength in different volumes of 60Si2CrVA spring steel. Predicted fatigue strength was in accordance with experimental results by ultrasonic fatigue testing.
基金supported by the National Natural Science Foundation of China(No.82272421)the Jiangsu Provincial Key Research and Development Program(No.BE2021690)+2 种基金the Changzhou's 14th Five-year Plan Project to Train Highlevel Health Professionals(No.2022CZLJ027)the Scientific Project of Jiangsu Health Commission(No.Z2020038)the Changzhou Sci&Tech Program(No.CJ20220164),China.
文摘Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.
文摘Laayoune and the Foum El Oued aquifers are in hydraulic communication only at the level of Oued Saguia El Hamra. The present study has accordingly made use of all the hydrogeological, hydrological, geological and geophysical data that preceded the watershed of Oued Saguia El Hamra in its downstream part. These data are by no means omplementary with the objective of having a better understanding of the boundary line between Laayoune and Foum El Oued aquifers and the origin of feeding the sources of Oued Saguia El Hamra. This study will focus only on the previous geophysical studies where a reinterpretation of electrical soundings has proved useful as a result of the recent well-logging results. It makes it possible to highlight the presence of a significant rise in the truncated marly substratum of Oued Saguia El Hamra and depressions (left and right banks) which could correspond to stream channels or depressed areas. At the level of the Wadi bed, there has been a regular immersion of the conductive level roofs from east to west towards Foum El Oued favoring the flow of wastewater from the zone and spraying the brackish water sources towards the groundwater of Foum El Oued. In the light of the reinterpretation of electric polls, plus as well as the geophysical surveys by electrical tomography and high definition made at the right and left banks of the Oueed Saguia El-Hamra, it was possible to verify the existence of dry ridge separating the two webs of Laayoune and Foum El Oued and stream channels or depressed areas of the left bank for drainage of brackish water to sources located along Oued Saguia El Hamra. The true resistivity models tomography profiles confirm the presence of the backbone at the left and right banks and the graben of the left bank for underground water drainage of the web Laayoune to sources welling the river Saguia El Hamra. They reveal the presence of a quaternary plio-cover (coastal platform Moghrebian) as being heterogeneous and affected by many electrical discontinuities, particularly in the level resistant R2 (coquina sandstone). These discontinuities could correspond to lateral changes in facies and/or synsedimental faults compartmentalizing the plio-quaternary formations into a system of Horsts and Grabens that relies on the whole (D1, Cs) attributed to formations from the Miocene to the Upper Cretaceous. The contours of the map show the distribution of the three families of electrical soundings A, B and C limited by two main electrical discontinuities D and M. East of discontinuity million, this map reflects the look of the wall of the Pliocene-Quaternary resting on the impermeable upper Cretaceous floor. To the west of this electrical discontinuity M, the map reflects the behavior of the roof of marl deposits of Miocene age.
基金supported by the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(31971266,51232002)+1 种基金the Key Research and Development Program of Guangzhou(202007020002)Guangdong Province Basic and Applied Research Foundation(2022A1515011925).
文摘The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracellular vesicles(sEVs)derived from mesenchymal stem cells hold great potential in tissue repair.Nevertheless,the poor homing and retention of sEVs greatly limited their possible clinical application.In the present work,DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs(CREKA-sEVs),which could target fibrin to accumulate and retain in bone defects.Our results showed that CREKA-sEVs,like sEVs,promoted the osteogenic differentiation of BMSCs,the angiogenic property of HUVECs,and modulated the polarization of macrophages in vitro.Furthermore,due to the improved fibrin-binding and retention capacity of CREKA-sEVs,they enhanced the bone repair substantially in the rat femoral defect model.This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.
基金supported by Fund of Shaanxi Science and Technology Research and Development Plan Project(2015GY073)Shaanxi Key Research and Development Program(2019GY-057).
文摘This paper presents a comprehensive survey on the development of Intel SGX(software guard extensions)processors and its applications.With the advent of SGX in 2013 and its subsequent development,the corresponding research works are also increasing rapidly.In order to get a more comprehensive literature review related to SGX,we have made a systematic analysis of the related papers in this area.We first search through five large-scale paper retrieval libraries by keywords(i.e.,ACM Digital Library,IEEE/IET Electronic Library,SpringerLink,Web of Science,and Elsevier Science Direct).We read and analyze a total of 128 SGX-related papers.The first round of extensive study is conducted to classify them.The second round of intensive study is carried out to complete a comprehensive analysis of the paper from various aspects.We start with the working environment of SGX and make a conclusive summary of trusted execution environment(TEE).We then focus on the applications of SGX.We also review and study multifarious attack methods to SGX framework and some recent security improvements made on SGX.Finally,we summarize the advantages and disadvantages of SGX with some future research opportunities.We hope this review could help the existing and future research works on SGX and its application for both developers and users.
