The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerat...The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-ofthe-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on micro RNA-mediated reprogramming. Additionally, we discuss current advances on state-of-theart targeted drug delivery systems that can be employed to deliver these micro RNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in micro RNAbased therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.展开更多
DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage ...DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence.展开更多
In this paper, seeds of pinus koraiensis which has a characteristic of deep dormancy were selected as an experiment material, and the relation of cellular substance exudation to seed vigour is discussed based on the d...In this paper, seeds of pinus koraiensis which has a characteristic of deep dormancy were selected as an experiment material, and the relation of cellular substance exudation to seed vigour is discussed based on the dormant state, the different measuring parts and the imbibed state of seeds before testing, as well as on the respiration of embryo and endosperm. The major measured results arc as follows: (1) After soaking for 24h, the dry embryo conductivity of sccdlot L is greater that than of sccdlot H: (2) The substance exudation of dry embryo of sccdlot H is less than that of sccdlot L; (3) After seeds imbibed, the substance exudation of dormant embryo of sccdlot H is more than that of sccdlot L; (4) After germination hastening treatment, the substance exudation of H embryos is greater than that of L embryos; (5) After artificially accelerated ageing treatment, the embryo conductivity of imbibed seeds has a positive correlation with seed vigour.展开更多
Background: The skin serves as the first line of defense for the human body. Direct sunlight contains damaging radiations that can speed up the ageing process of the skin, resulting in wrinkles, leathery skin, dark pa...Background: The skin serves as the first line of defense for the human body. Direct sunlight contains damaging radiations that can speed up the ageing process of the skin, resulting in wrinkles, leathery skin, dark patches, and solar elastosis. Objectives: To evaluate the effect of multiple solar irradiation related factors at the protein level in human dermal fibroblast (HDF). The overall effect of individual solar irradiations such as Infrared A (IRA), blue light (BL), UVA, and UVB on HDF cells and the extent of molecular level aberrations to be assessed and compared against each. Methods: Label-free quantitative proteomics (MS/MS) approach has been adopted in this study to observe the protein level changes induced in the HDF cells through various exposures of full light sources. Following that, downstream insilico analysis has been carried out. Results: In this study, it is demonstrated all the four different solar irradiations significantly contribute to the molecular degeneration of skin cells through various mechanisms. This study confirms that BL down-regulates DNA repair proteins and the skin cells-HDF stimulate the histone proteins as a response mechanism to maintain the chromosomal integrity. Conclusions: The proteomics experiment carried out in the current study intends to support the future sun care products based on full light protection technology that can be custom designed to provide complete protection from the solar radiation. Similar technology could enhance the further investigations for deeper understanding of induction, mode of action, and prevention of skin damage from extensive solar irradiation.展开更多
为改善汽车吸能盒在低速碰撞情况下的力学表现,将一种新型具有负泊松比效应的多胞结构设计为汽车前纵梁的吸能盒.通过对新型负泊松比多胞结构形状参数的研究,确立了多胞结构中特定的元胞几何参数及元胞层数作为优化变量,结构质量以及所...为改善汽车吸能盒在低速碰撞情况下的力学表现,将一种新型具有负泊松比效应的多胞结构设计为汽车前纵梁的吸能盒.通过对新型负泊松比多胞结构形状参数的研究,确立了多胞结构中特定的元胞几何参数及元胞层数作为优化变量,结构质量以及所吸收的能量作为优化目标.首先通过最优拉丁超立方的方法在变量空间内进行样本点的选取并采用ABAQUS进行有限元仿真计算,然后由Isight软件根据样本点的计算结果对优化变量与优化目标建立三阶响应面模型,最终采用NCGA对响应面模型进行优化.将优化结果进行RCAR(Research Council for Automobile Repairs)标准模型仿真计算,结果验证了这一新型负泊松比吸能盒可以在较小的质量下满足RCAR低速碰撞标准.展开更多
Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic.Up to now,none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve func...Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic.Up to now,none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function.This restriction is also effective for novel clinically approved artificial nerve guides.In this review,we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and shortcomings.We furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides,for which our own studies contributed to their approval for clinical use.In the second part of this review,very recent future perspectives for the enhancement of tubular(commonly hollow)nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve structure.This includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures,hydrogels,growth factors,and approaches of cell transplantation.Additionally,we highlight upcoming future perspectives comprising co-application of stem cell secretome.From our overview,we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental studies.But for bringing nerve repair with bioartificial nerve grafts to the next level,e.g.repair of defects>3 cm in human patients,more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.展开更多
文摘The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-ofthe-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on micro RNA-mediated reprogramming. Additionally, we discuss current advances on state-of-theart targeted drug delivery systems that can be employed to deliver these micro RNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in micro RNAbased therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.
基金was supported by the National Natural Science Foundation of China (No.31130017, 31071190, and 30711120570)the 973 project 2010CB911904+1 种基金Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality (No. PHR20110508) to XXthe 973 project 2012CB911203 to YSC
文摘DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence.
文摘In this paper, seeds of pinus koraiensis which has a characteristic of deep dormancy were selected as an experiment material, and the relation of cellular substance exudation to seed vigour is discussed based on the dormant state, the different measuring parts and the imbibed state of seeds before testing, as well as on the respiration of embryo and endosperm. The major measured results arc as follows: (1) After soaking for 24h, the dry embryo conductivity of sccdlot L is greater that than of sccdlot H: (2) The substance exudation of dry embryo of sccdlot H is less than that of sccdlot L; (3) After seeds imbibed, the substance exudation of dormant embryo of sccdlot H is more than that of sccdlot L; (4) After germination hastening treatment, the substance exudation of H embryos is greater than that of L embryos; (5) After artificially accelerated ageing treatment, the embryo conductivity of imbibed seeds has a positive correlation with seed vigour.
文摘Background: The skin serves as the first line of defense for the human body. Direct sunlight contains damaging radiations that can speed up the ageing process of the skin, resulting in wrinkles, leathery skin, dark patches, and solar elastosis. Objectives: To evaluate the effect of multiple solar irradiation related factors at the protein level in human dermal fibroblast (HDF). The overall effect of individual solar irradiations such as Infrared A (IRA), blue light (BL), UVA, and UVB on HDF cells and the extent of molecular level aberrations to be assessed and compared against each. Methods: Label-free quantitative proteomics (MS/MS) approach has been adopted in this study to observe the protein level changes induced in the HDF cells through various exposures of full light sources. Following that, downstream insilico analysis has been carried out. Results: In this study, it is demonstrated all the four different solar irradiations significantly contribute to the molecular degeneration of skin cells through various mechanisms. This study confirms that BL down-regulates DNA repair proteins and the skin cells-HDF stimulate the histone proteins as a response mechanism to maintain the chromosomal integrity. Conclusions: The proteomics experiment carried out in the current study intends to support the future sun care products based on full light protection technology that can be custom designed to provide complete protection from the solar radiation. Similar technology could enhance the further investigations for deeper understanding of induction, mode of action, and prevention of skin damage from extensive solar irradiation.
文摘为改善汽车吸能盒在低速碰撞情况下的力学表现,将一种新型具有负泊松比效应的多胞结构设计为汽车前纵梁的吸能盒.通过对新型负泊松比多胞结构形状参数的研究,确立了多胞结构中特定的元胞几何参数及元胞层数作为优化变量,结构质量以及所吸收的能量作为优化目标.首先通过最优拉丁超立方的方法在变量空间内进行样本点的选取并采用ABAQUS进行有限元仿真计算,然后由Isight软件根据样本点的计算结果对优化变量与优化目标建立三阶响应面模型,最终采用NCGA对响应面模型进行优化.将优化结果进行RCAR(Research Council for Automobile Repairs)标准模型仿真计算,结果验证了这一新型负泊松比吸能盒可以在较小的质量下满足RCAR低速碰撞标准.
文摘Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic.Up to now,none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function.This restriction is also effective for novel clinically approved artificial nerve guides.In this review,we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and shortcomings.We furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides,for which our own studies contributed to their approval for clinical use.In the second part of this review,very recent future perspectives for the enhancement of tubular(commonly hollow)nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve structure.This includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures,hydrogels,growth factors,and approaches of cell transplantation.Additionally,we highlight upcoming future perspectives comprising co-application of stem cell secretome.From our overview,we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental studies.But for bringing nerve repair with bioartificial nerve grafts to the next level,e.g.repair of defects>3 cm in human patients,more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.
