Background:Acute pancreatitis(AP)is a severe disorder that leads to high morbidity and mortality.Appropriate reference genes are important for gene analysis in AP.This study sought to study the expression stability of...Background:Acute pancreatitis(AP)is a severe disorder that leads to high morbidity and mortality.Appropriate reference genes are important for gene analysis in AP.This study sought to study the expression stability of several reference genes in the golden Syrian hamster,a model of AP.Methods:AP was induced in golden Syrian hamster by intraperitoneal injection of ethanol(1.35 g/kg)and palmitoleic acid(2 mg/kg).The expression of candidate genes,including Actb,Gapdh,Eef2,Ywhaz,Rps18,Hprt1,Tubb,Rpl13a,Nono,and B2m,in hamster pancreas at different time points(1,3,6,9,and 24 h)posttreatment was analyzed using quantitative polymerase chain reaction.The expression stability of these genes was calculated using Best Keeper,Comprehensive Delta CT,Norm Finder,and ge Norm algorithms and Ref Finder software.Results:Our results show that the expression of these reference genes fluctuated during AP,of which Ywhaz and Gapdh were the most stable genes,whereas Tubb,Eef2,and Actb were the least stable genes.Furthermore,these genes were used to normalize the expression of TNF-αmessenger ribonucleic acid in inflamed pancreas.Conclusions:In conclusion,Ywhaz and Gapdh were suitable reference genes for gene expression analysis in AP induced in Syrian hamster.展开更多
Tissue engineering is an emerging means for resolving the problems of tissue repair and organ replacement in regenerative medicine.Insufficient supply of nutrients and oxygen to cells in large-scale tissues has led to...Tissue engineering is an emerging means for resolving the problems of tissue repair and organ replacement in regenerative medicine.Insufficient supply of nutrients and oxygen to cells in large-scale tissues has led to the demand to prepare blood vessels.Scaffold-based tissue engineering approaches are effective methods to form new blood vessel tissues.The demand for blood vessels prompts systematic research on fabrication strategies of vascular scaffolds for tissue engineering.Recent advances in 3D printing have facilitated fabrication of vascular scaffolds,contributing to broad prospects for tissue vascularization.This review presents state of the art on modeling methods,print materials and preparation processes for fabrication of vascular scaffolds,and discusses the advantages and application fields of each method.Specially,significance and importance of scaffold-based tissue engineering for vascular regeneration are emphasized.Print materials and preparation processes are discussed in detail.And a focus is placed on preparation processes based on 3D printing technologies and traditional manufacturing technologies including casting,electrospinning,and Lego-like construction.And related studies are exemplified.Transformation of vascular scaffolds to clinical application is discussed.Also,four trends of 3D printing of tissue engineering vascular scaffolds are presented,including machine learning,near-infrared photopolymerization,4D printing,and combination of self-assembly and 3D printing-based methods.展开更多
We present a method for computed tomography(CT)image processing and modeling for tibia microstructure,achieved by using computer graphics and fractal theory.Given the large-scale image data of tibia species with DICOM...We present a method for computed tomography(CT)image processing and modeling for tibia microstructure,achieved by using computer graphics and fractal theory.Given the large-scale image data of tibia species with DICOM standard for clinical applications,we take advantage of algorithms such as image binarization,hot pixel removing and close operation to obtain visually clear image for tibia microstructure.All of these images are based on 20 CT scanning images with 30μm slice thickness and 30μm interval and continuous changes in pores.For each pore,we determine its profile by using an improved algorithm for edge detection.Then,to calculate its three-dimensional fractal dimension,we measure the circumference perimeter and area of the pores of bone microstructure using a line fitting method based on the least squares.Subsequently,we put forward an algorithm for the pore profiles through ellipse fitting.The results show that the pores have significant fractal characteristics because of the good linear correlation between the perimeter and the area parameters in log–log scale coordinates system,and the ratio of the elliptical short axis to the long axis through ellipse fitting tends to 0.6501.Based on support vector machine and structural risk minimization principle,we put forward a mapping database theory of structure parameters among the pores of CT images and fractal dimension,Poisson’s ratios,porosity and equivalent aperture.On this basis,we put forward a new concept for 3D modeling called precision-measuring digital expressing to reconstruct tibia microstructure for human hard tissue.展开更多
Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenv...Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment(TME)and systemic toxicity caused by excessive cytokine release.As a key regulator of the immunosuppressive TME,TGF-βpromotes cytokine synthesis via the NF-κB pathway.Here,we coexpressed SMAD7,a suppressor of TGF-βsignaling,with a HER2-targeted CAR in engineered T cells.These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion,which enabled sustained tumoricidal capacity after continuous antigen exposure.Moreover,SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells.Mechanistically,SMAD7 downregulated TGF-βreceptor I and abrogated the interplay between the TGF-βand NF-κB pathways in CAR-T cells.As a result,these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β.SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids.Therefore,our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.展开更多
T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed.It can cause gastrointestinal toxicity,hepatotoxicity,immunotoxicity,reproductive toxicity,neurotoxicity,and nephrotoxicity in humans an...T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed.It can cause gastrointestinal toxicity,hepatotoxicity,immunotoxicity,reproductive toxicity,neurotoxicity,and nephrotoxicity in humans and animals.T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing.Therefore,suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue.Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature,but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized.In this review,we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects.Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option.This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.展开更多
Ti/Al/Mg laminated composites were successfully fabricated by hot roll bonding.The effects of the rolling reduction on the microstructural evolution and mechanical properties of the composites were explored.The result...Ti/Al/Mg laminated composites were successfully fabricated by hot roll bonding.The effects of the rolling reduction on the microstructural evolution and mechanical properties of the composites were explored.The results show that Ti/Al/Mg laminated sheets exhibit good interfacial bonding.The rolling reduction has a significant effect on the deformation inhomogeneity through the thickness of the Al layer.The initial grains of the Al layer near the Ti/Al interface are fragmented into fine equiaxed grains,and the grains at the center and near the Al/Mg interface are elongated.The R-cube shear texture of the Al layer forms near the Ti/Al interface and permeates into the center layer in the samples with greater rolling reductions.The b-fiber rolling texture of the Al layer is observed near the Al/Mg interface and increases with the increase of rolling reduction.The stress–strain curves indicate that the fracture appears first in the Mg layer.With the increasing rolling reduction,the ultimate tensile and yield strength values increase,and the elongation up to the Mg layer fracture decreases.展开更多
Here,we report a density functional theory(DFT)-based high-throughput screening method to successfully identify a type of alloy nanoclusters as the electrocatalyst for hydrogen evolution reaction(HER).Totally 7924 can...Here,we report a density functional theory(DFT)-based high-throughput screening method to successfully identify a type of alloy nanoclusters as the electrocatalyst for hydrogen evolution reaction(HER).Totally 7924 candidates of Cu-based alloy clusters of Cu55-nMn(M=Co,Ni,Ru,and Rh)are optimized and evaluated to screening for the promising catalysts.By comparing different structural patterns,Cu-based alloy clusters prefer the core–shell structures with the dopant metal in the core and Cu as the shell atoms.Generally speaking,the HER performance of the Cu-based nanoclusters can be significantly improved by doping transition metals,and the active sites are the bridge sites and three-fold sites on the outer-shell Cu atoms.Considering the structural stability and the electrochemical activity,core–shell CuNi alloy clusters are suggested to be the superior electrocatalyst for hydrogen evolution.A descriptor composing of surface charge is proposed to efficiently evaluate the HER activity of the alloy clusters supported by the DFT calculations and machine-learning techniques.Our screening strategy could accelerate the pace of discovery for promising HER electrocatalysts using metal alloy nanoclusters.展开更多
The demand for artificial organs has greatly increased because of various aging-associated diseases and the wide need for organ transplants.A recent trend in tissue engineering is the precise reconstruction of tissues...The demand for artificial organs has greatly increased because of various aging-associated diseases and the wide need for organ transplants.A recent trend in tissue engineering is the precise reconstruction of tissues by the growth of cells adhering to bioscaffolds,which are three-dimensional(3D)structures that guide tissue and organ formation.Bioscaffolds used to fabricate bionic tissues should be able to not only guide cell growth but also regulate cell behaviors.Common regulation methods include biophysical and biochemical stimulations.Biophysical stimulation cues include matrix hardness,external stress and strain,surface topology,and electromagnetic field and concentration,whereas biochemical stimulation cues include growth factors,proteins,kinases,and magnetic nanoparticles.This review discusses bioink preparation,3D bioprinting(including extrusion-based,inkjet,and ultraviolet-assisted 3D bioprinting),and regulation of cell behaviors.In particular,it provides an overview of state-of-the-art methods and devices for regulating cell growth and tissue formation and the effects of biophysical and biochemical stimulations on cell behaviors.In addition,the fabrication of bioscaffolds embedded with regulatory modules for biomimetic tissue preparation is explained.Finally,challenges in cell growth regulation and future research directions are presented.展开更多
基金China Postdoctoral Science Foundation,Grant/Award Number:2021T140184Program for Science Technology Innovation Talents in Universities of Henan Province,Grant/Award Number:23HASTIT045Scientific Research of Traditional Chinese Medicine Specialized in Henan Province,Grant/Award Number:2022ZY1172。
文摘Background:Acute pancreatitis(AP)is a severe disorder that leads to high morbidity and mortality.Appropriate reference genes are important for gene analysis in AP.This study sought to study the expression stability of several reference genes in the golden Syrian hamster,a model of AP.Methods:AP was induced in golden Syrian hamster by intraperitoneal injection of ethanol(1.35 g/kg)and palmitoleic acid(2 mg/kg).The expression of candidate genes,including Actb,Gapdh,Eef2,Ywhaz,Rps18,Hprt1,Tubb,Rpl13a,Nono,and B2m,in hamster pancreas at different time points(1,3,6,9,and 24 h)posttreatment was analyzed using quantitative polymerase chain reaction.The expression stability of these genes was calculated using Best Keeper,Comprehensive Delta CT,Norm Finder,and ge Norm algorithms and Ref Finder software.Results:Our results show that the expression of these reference genes fluctuated during AP,of which Ywhaz and Gapdh were the most stable genes,whereas Tubb,Eef2,and Actb were the least stable genes.Furthermore,these genes were used to normalize the expression of TNF-αmessenger ribonucleic acid in inflamed pancreas.Conclusions:In conclusion,Ywhaz and Gapdh were suitable reference genes for gene expression analysis in AP induced in Syrian hamster.
文摘Tissue engineering is an emerging means for resolving the problems of tissue repair and organ replacement in regenerative medicine.Insufficient supply of nutrients and oxygen to cells in large-scale tissues has led to the demand to prepare blood vessels.Scaffold-based tissue engineering approaches are effective methods to form new blood vessel tissues.The demand for blood vessels prompts systematic research on fabrication strategies of vascular scaffolds for tissue engineering.Recent advances in 3D printing have facilitated fabrication of vascular scaffolds,contributing to broad prospects for tissue vascularization.This review presents state of the art on modeling methods,print materials and preparation processes for fabrication of vascular scaffolds,and discusses the advantages and application fields of each method.Specially,significance and importance of scaffold-based tissue engineering for vascular regeneration are emphasized.Print materials and preparation processes are discussed in detail.And a focus is placed on preparation processes based on 3D printing technologies and traditional manufacturing technologies including casting,electrospinning,and Lego-like construction.And related studies are exemplified.Transformation of vascular scaffolds to clinical application is discussed.Also,four trends of 3D printing of tissue engineering vascular scaffolds are presented,including machine learning,near-infrared photopolymerization,4D printing,and combination of self-assembly and 3D printing-based methods.
基金supported by the National Key Research and Development Program of China(No.2016YFC1100600)the National Nature Science Foundation of China(Nos.61540006,61672363).
文摘We present a method for computed tomography(CT)image processing and modeling for tibia microstructure,achieved by using computer graphics and fractal theory.Given the large-scale image data of tibia species with DICOM standard for clinical applications,we take advantage of algorithms such as image binarization,hot pixel removing and close operation to obtain visually clear image for tibia microstructure.All of these images are based on 20 CT scanning images with 30μm slice thickness and 30μm interval and continuous changes in pores.For each pore,we determine its profile by using an improved algorithm for edge detection.Then,to calculate its three-dimensional fractal dimension,we measure the circumference perimeter and area of the pores of bone microstructure using a line fitting method based on the least squares.Subsequently,we put forward an algorithm for the pore profiles through ellipse fitting.The results show that the pores have significant fractal characteristics because of the good linear correlation between the perimeter and the area parameters in log–log scale coordinates system,and the ratio of the elliptical short axis to the long axis through ellipse fitting tends to 0.6501.Based on support vector machine and structural risk minimization principle,we put forward a mapping database theory of structure parameters among the pores of CT images and fractal dimension,Poisson’s ratios,porosity and equivalent aperture.On this basis,we put forward a new concept for 3D modeling called precision-measuring digital expressing to reconstruct tibia microstructure for human hard tissue.
基金supported by a grant from the National Natural Science Foundation of China(No.81972870)the Independent Research Topic of State Key Laboratory of Cancer Biology of Fourth Military Medical University(CBSKL2022ZZ20)+2 种基金Shaanxi Innovative Research Team for Key Science and Technology(S2022-ZC-TD-0065)the Natural Science Foundation of Henan Province(No.222300420264)Tangdu Hospital-key research project(2022TDGS007).
文摘Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment(TME)and systemic toxicity caused by excessive cytokine release.As a key regulator of the immunosuppressive TME,TGF-βpromotes cytokine synthesis via the NF-κB pathway.Here,we coexpressed SMAD7,a suppressor of TGF-βsignaling,with a HER2-targeted CAR in engineered T cells.These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion,which enabled sustained tumoricidal capacity after continuous antigen exposure.Moreover,SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells.Mechanistically,SMAD7 downregulated TGF-βreceptor I and abrogated the interplay between the TGF-βand NF-κB pathways in CAR-T cells.As a result,these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β.SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids.Therefore,our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.
基金supported by the Doctoral Initiation Fund Project Grant(BK202315)Medical Research Special Fund(2022YKY17)of Hubei University of Science and TechnologyHubei Provincial Natural Science Foundation Programme(2023AFB537)
文摘T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed.It can cause gastrointestinal toxicity,hepatotoxicity,immunotoxicity,reproductive toxicity,neurotoxicity,and nephrotoxicity in humans and animals.T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing.Therefore,suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue.Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature,but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized.In this review,we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects.Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option.This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.
基金financial supports from the National Natural Science Foundation of China(No.51421001)the National High Technology Research and Development Program of China(863 Program,No.2013AA031304)+1 种基金the Fundamental Research Funds for the CentralUniversitiesofChina(2019CDQYCL001,2019CDCGCL204,2020CDJDPT001)the Research Project of State Key Laboratory of Vehicle NVH and Safety Technology of China(No.NVHSKL-201706)。
文摘Ti/Al/Mg laminated composites were successfully fabricated by hot roll bonding.The effects of the rolling reduction on the microstructural evolution and mechanical properties of the composites were explored.The results show that Ti/Al/Mg laminated sheets exhibit good interfacial bonding.The rolling reduction has a significant effect on the deformation inhomogeneity through the thickness of the Al layer.The initial grains of the Al layer near the Ti/Al interface are fragmented into fine equiaxed grains,and the grains at the center and near the Al/Mg interface are elongated.The R-cube shear texture of the Al layer forms near the Ti/Al interface and permeates into the center layer in the samples with greater rolling reductions.The b-fiber rolling texture of the Al layer is observed near the Al/Mg interface and increases with the increase of rolling reduction.The stress–strain curves indicate that the fracture appears first in the Mg layer.With the increasing rolling reduction,the ultimate tensile and yield strength values increase,and the elongation up to the Mg layer fracture decreases.
基金This work was supported by the National Key Research and Development Program of China(Grant nos.2018YFB0703900,2017YFA0204800,and 2017YFB0701600)the National Natural Science Foundation of China(91961204 and 21973067).
文摘Here,we report a density functional theory(DFT)-based high-throughput screening method to successfully identify a type of alloy nanoclusters as the electrocatalyst for hydrogen evolution reaction(HER).Totally 7924 candidates of Cu-based alloy clusters of Cu55-nMn(M=Co,Ni,Ru,and Rh)are optimized and evaluated to screening for the promising catalysts.By comparing different structural patterns,Cu-based alloy clusters prefer the core–shell structures with the dopant metal in the core and Cu as the shell atoms.Generally speaking,the HER performance of the Cu-based nanoclusters can be significantly improved by doping transition metals,and the active sites are the bridge sites and three-fold sites on the outer-shell Cu atoms.Considering the structural stability and the electrochemical activity,core–shell CuNi alloy clusters are suggested to be the superior electrocatalyst for hydrogen evolution.A descriptor composing of surface charge is proposed to efficiently evaluate the HER activity of the alloy clusters supported by the DFT calculations and machine-learning techniques.Our screening strategy could accelerate the pace of discovery for promising HER electrocatalysts using metal alloy nanoclusters.
基金supported by the Innovative Public Service Center of High-End Manufacturing Technology for Technical Service of High-Tech Zone,Qiqihar,China.
文摘The demand for artificial organs has greatly increased because of various aging-associated diseases and the wide need for organ transplants.A recent trend in tissue engineering is the precise reconstruction of tissues by the growth of cells adhering to bioscaffolds,which are three-dimensional(3D)structures that guide tissue and organ formation.Bioscaffolds used to fabricate bionic tissues should be able to not only guide cell growth but also regulate cell behaviors.Common regulation methods include biophysical and biochemical stimulations.Biophysical stimulation cues include matrix hardness,external stress and strain,surface topology,and electromagnetic field and concentration,whereas biochemical stimulation cues include growth factors,proteins,kinases,and magnetic nanoparticles.This review discusses bioink preparation,3D bioprinting(including extrusion-based,inkjet,and ultraviolet-assisted 3D bioprinting),and regulation of cell behaviors.In particular,it provides an overview of state-of-the-art methods and devices for regulating cell growth and tissue formation and the effects of biophysical and biochemical stimulations on cell behaviors.In addition,the fabrication of bioscaffolds embedded with regulatory modules for biomimetic tissue preparation is explained.Finally,challenges in cell growth regulation and future research directions are presented.