Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates sub...Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.展开更多
With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely app...With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely applied to the treatment of diseases related to tissue or organ replacement in dentistry,respectively.However,there are very few studies on the combination of the two,and even fewer clinical studies have been reported in dentistry.In this review,the current oral tissue engineering in vivo and in vitro based on 3D printing and stem cell technology will be summarized,and the discussion on the development prospects of this research direction will be given.Besides,the working principles and advantages&disadvantages of several types of 3D printers,as well as the mechanism of stem cells in tissue engineering will be elucidated.This review provides clinicians and researchers with the current state of research and trends in the combination of stem cells and 3D printing technology to treat oral-related diseases.In the future,3D bioprinters are poised for ongoing innovation with the advancement of relevant technologies,catalyzing an increase in clinical studies focused on treating oral diseases using stem cells and 3D scaffolds.Consequently,these developments will further advance the field of oral tissue engineering.展开更多
Cymbidium goeringii is an economically important ornamental plant,and flower color is one of the main features of C.goeringii that contributes to its high economic value.To clarify the molecular mechanisms underlying ...Cymbidium goeringii is an economically important ornamental plant,and flower color is one of the main features of C.goeringii that contributes to its high economic value.To clarify the molecular mechanisms underlying the role of anthocyanins in mediating differences in color among varieties,liquid chromatography–tandem mass spectrometry was used to perform anthocyanin-targeted metabolomics of seven C.goeringii varieties,including‘Jin Qian Yuan’(JQY),‘Jin Xiu Qian Yuan’(JXQY),‘Miao Jiang Su Die’(MJSD),‘Qian Ming Su’(QMS),‘Shi Chan’(SC),and‘Yang Ming Su’(YMS),as well as the C.goeringii.We detected 64 anthocyanins,including cyanidins,delphinidins,malvidins,pelargonidins,peonidins,petunidins,procyanidins,and flavonoids.We identified six shared differentially accumulated metabolites(DAMs),including cyanidin-3-O-rutinoside,delphinidin-3-Osophoroside,pelargonidin-3-O-rutinoside,peonidin-3-O-(6-O-malonyl-beta-D-glucoside),peonidin-3-Osophoroside,and chalcone.Most DAMs were enriched in the anthocyanin biosynthesis pathway.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed metabolites were significantly enriched in the anthocyanin biosynthesis pathway.Analysis of the content of differentially expressed metabolites indicated that peonidin-3-O-(6-O-malonyl-beta-D-glucoside)was the key metabolite underlying color differences among C.goeringii varieties.Procyanidin B2,pelargonidin-3-O-galactoside,and naringenin might also affect the color formation of JQY and QMS,SC,and MJSD,respectively.The results of this study shed light on the metabolic mechanism underlying flower color differences in C.goeringii at the molecular level.Our findings will aid future studies of the mechanism of flower color regulation in C.goeringii and have implications for the breeding of new varieties.展开更多
Low stiffness and positioning problems are difficulties and challenges in the precise machining of near-net-shaped blades.This paper aims to achieve high accuracy in manufacturing by fixture-and deformation-control in...Low stiffness and positioning problems are difficulties and challenges in the precise machining of near-net-shaped blades.This paper aims to achieve high accuracy in manufacturing by fixture-and deformation-control in the adaptive CNC machining process.Adaptive CNC machining technology is first analyzed,and new fixture-evaluation criteria and methods to evaluate the adaptive CNC machining process fixture design are built.Second,a machining fixture is designed and manufactured after analyzing its positioning scheme,clamping scheme,materials(PEEK-GF30),and structure characteristics.Finally,the designed fixture is analyzed by FEA and experimentally verified by a cutting experiment.The results show that the deformation of the blade is an overall rigid-body displacement,the main deformation of the blade-fixture system occurs on the four clamping heads,and this fixture can effectively protect the blade from local deformation.The proposed clamping-sequence method reliably and effectively controls the local maximum deformation of the blade.The system stiffness is increased by 20 Hz,with each clamping force increased by 200 N.Both high-and low-frequency displacement in roughing milling or finishing milling are acceptable relative to the accuracy demand of blade machining.This fixture and an adaptive CNC machining process can achieve high accuracy in blade manufacturing.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:82174292Key Project of Jiangsu Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:ZD202312+2 种基金Natural Science Foundation of Laboratory Medicine School in Chengdu Medical College,Grant/Award Number:JYZK202203Sichuan Province Science and Technology Program,Grant/Award Number:2024NSFSC0577 and 2021YFG0316Technology innovation group project of Foshan 2019,Grant/Award Number:FS0AA-KJ919-4402-0027。
文摘Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.
基金supported by 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD23030)National Natural Science Foundation of China(No.82172254)Science and Technological Supports Project of Sichuan Province,China(No.2024YFFK0214).
文摘With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely applied to the treatment of diseases related to tissue or organ replacement in dentistry,respectively.However,there are very few studies on the combination of the two,and even fewer clinical studies have been reported in dentistry.In this review,the current oral tissue engineering in vivo and in vitro based on 3D printing and stem cell technology will be summarized,and the discussion on the development prospects of this research direction will be given.Besides,the working principles and advantages&disadvantages of several types of 3D printers,as well as the mechanism of stem cells in tissue engineering will be elucidated.This review provides clinicians and researchers with the current state of research and trends in the combination of stem cells and 3D printing technology to treat oral-related diseases.In the future,3D bioprinters are poised for ongoing innovation with the advancement of relevant technologies,catalyzing an increase in clinical studies focused on treating oral diseases using stem cells and 3D scaffolds.Consequently,these developments will further advance the field of oral tissue engineering.
基金supported by the Study on Resource Collection and New Variety Breeding of the Guizhou Mountainous Characteristic Flower C.goeringii(QianKeHe[2022]General 107)the Key Laboratory of National Forestry and Grassland Administration on Biodiversity Conservation in Karst Mountainous Areas of Southwestern China,Guizhou Academy of Forestry.
文摘Cymbidium goeringii is an economically important ornamental plant,and flower color is one of the main features of C.goeringii that contributes to its high economic value.To clarify the molecular mechanisms underlying the role of anthocyanins in mediating differences in color among varieties,liquid chromatography–tandem mass spectrometry was used to perform anthocyanin-targeted metabolomics of seven C.goeringii varieties,including‘Jin Qian Yuan’(JQY),‘Jin Xiu Qian Yuan’(JXQY),‘Miao Jiang Su Die’(MJSD),‘Qian Ming Su’(QMS),‘Shi Chan’(SC),and‘Yang Ming Su’(YMS),as well as the C.goeringii.We detected 64 anthocyanins,including cyanidins,delphinidins,malvidins,pelargonidins,peonidins,petunidins,procyanidins,and flavonoids.We identified six shared differentially accumulated metabolites(DAMs),including cyanidin-3-O-rutinoside,delphinidin-3-Osophoroside,pelargonidin-3-O-rutinoside,peonidin-3-O-(6-O-malonyl-beta-D-glucoside),peonidin-3-Osophoroside,and chalcone.Most DAMs were enriched in the anthocyanin biosynthesis pathway.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed metabolites were significantly enriched in the anthocyanin biosynthesis pathway.Analysis of the content of differentially expressed metabolites indicated that peonidin-3-O-(6-O-malonyl-beta-D-glucoside)was the key metabolite underlying color differences among C.goeringii varieties.Procyanidin B2,pelargonidin-3-O-galactoside,and naringenin might also affect the color formation of JQY and QMS,SC,and MJSD,respectively.The results of this study shed light on the metabolic mechanism underlying flower color differences in C.goeringii at the molecular level.Our findings will aid future studies of the mechanism of flower color regulation in C.goeringii and have implications for the breeding of new varieties.
基金supported in part by Xi’an Aero-Engine(Group)Ltd.National Key Scientific Instrument and Equipment Development Project(2016YFF0101900)+1 种基金National Natural Science Foundation of China(Grant 51575310)Beijing Municipal Natural Science Foundation(Grant 3162014)。
文摘Low stiffness and positioning problems are difficulties and challenges in the precise machining of near-net-shaped blades.This paper aims to achieve high accuracy in manufacturing by fixture-and deformation-control in the adaptive CNC machining process.Adaptive CNC machining technology is first analyzed,and new fixture-evaluation criteria and methods to evaluate the adaptive CNC machining process fixture design are built.Second,a machining fixture is designed and manufactured after analyzing its positioning scheme,clamping scheme,materials(PEEK-GF30),and structure characteristics.Finally,the designed fixture is analyzed by FEA and experimentally verified by a cutting experiment.The results show that the deformation of the blade is an overall rigid-body displacement,the main deformation of the blade-fixture system occurs on the four clamping heads,and this fixture can effectively protect the blade from local deformation.The proposed clamping-sequence method reliably and effectively controls the local maximum deformation of the blade.The system stiffness is increased by 20 Hz,with each clamping force increased by 200 N.Both high-and low-frequency displacement in roughing milling or finishing milling are acceptable relative to the accuracy demand of blade machining.This fixture and an adaptive CNC machining process can achieve high accuracy in blade manufacturing.
