溴结构域和超末端结构域(bromodomain and extra-terminal,BET)蛋白家族作为表观"阅读器",在哺乳动物发育过程中起着至关重要的作用。其家族内的各成员通过识别各种表观修饰并募集相应的功能复合物,对相关基因进行精密调控,...溴结构域和超末端结构域(bromodomain and extra-terminal,BET)蛋白家族作为表观"阅读器",在哺乳动物发育过程中起着至关重要的作用。其家族内的各成员通过识别各种表观修饰并募集相应的功能复合物,对相关基因进行精密调控,促使早期胚胎向特定方向分化和发育。另外,随着诱导性多潜能干细胞(induced pluripotent stem cell,iPSC)重编程技术发展,越来越多的研究发现BET蛋白家族在体细胞重编程中可能也占据着核心地位。本文总结了BET蛋白家族在哺乳动物发育和iPSC重编程中的作用,并对BET家族调控重编程的新机制进行了展望。展开更多
The garden pea(Pisum sativum L.)is a significant cool-season legume,serving as crucial food sources,animal feed,and industrial raw materials.The advancement of functional genomics over the past two decades has provide...The garden pea(Pisum sativum L.)is a significant cool-season legume,serving as crucial food sources,animal feed,and industrial raw materials.The advancement of functional genomics over the past two decades has provided substantial theoretical foundations and progress to pea breeding.Notably,the release of the pea reference genome has enhanced our understanding of plant architecture,symbiotic nitrogen fixation(SNF),flowering time,floral organ development,seed development,and stress resistance.However,a considerable gap remains between pea functional genomics and molecular breeding.This review summarizes the current advancements in pea functional genomics and breeding while highlighting the future challenges in pea molecular breeding.展开更多
Rational design of electrode meterials with unique core-shell nanostructures is of great significance for improving the electrochemical performance of supercapacitors. In this work, we prepare several CuCo_(2)O_(4)@Ni...Rational design of electrode meterials with unique core-shell nanostructures is of great significance for improving the electrochemical performance of supercapacitors. In this work, we prepare several CuCo_(2)O_(4)@Ni-Co-S composite electrodes by a controllable hydrothermal and electrodeposition route. Onedimensional nanowires can shorten the ions transport path, while two-dimensional nanosheets expose many active sites. This enables three-dimensional structured composite with high electrochemical activity. The as-prepared heterostructured materials show a specific of 1048 C/g at 1 A/g. It still maintains 75.6% of initial capacity after 20000 cycles at 10 A/g. The device delivers an energy density of 79.2 Wh/kg when the power density reaches to 2280 W/kg. Moreover, it possesses an excellent mechanical stability after repeated folding at different angles.展开更多
Mechanical loading is required for bone homeostasis,but the underlying mechanism is still unclear.Our previous studies revealed that the mechanical protein polycystin-1(PC1,encoded by Pkd1)is critical for bone formati...Mechanical loading is required for bone homeostasis,but the underlying mechanism is still unclear.Our previous studies revealed that the mechanical protein polycystin-1(PC1,encoded by Pkd1)is critical for bone formation.However,the role of PC1 in bone resorption is unknown.Here,we found that PC1directly regulates osteoclastogenesis and bone resorption.The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts,decreased bone resorption,and increased bone mass.A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease,which is mainly caused by loss-of-function mutation of the PKD1 gene,is associated with a lower risk of hip fracture than those with other chronic kidney diseases.Moreover,mice with osteoclastspecific knockout of Pkd1 showed complete resistance to unloading-induced bone loss.A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass.Pharmacological regulation of the PC1-TAZ axis alleviated unloading-and estrogen deficiency-induced bone loss.Thus,the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.展开更多
Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen product...Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen production from water.Herein,we report a CoCrFeNiAl high-entropy alloy(HEA)electrocatalyst with self-supported structure synthesized by mechanical alloying and spark plasma sintering(SPS)consolidation.The HEA after HF treatment and in situ electrochemical activation for 4000 cycles of cyclic voltammetry(HF-HEAa2)presents favourable activity with overpotential of 73 mV to reach a current density of 10 mA cm^(2) and a Tafel slope of 39.7 mV dec1.The alloy effect of Al/Cr with Co/Fe/Ni at atomic level,high-temperature crystallization,as well as consolidation by SPS endow CoCrFeNiAl HEA with high stability in 0.5 M H2SO4 solution.The superior performance of HF-HEAa2 is related with the presence of metal hydroxides/oxides groups on HEA.展开更多
Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus rema...Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus remains unclear which hepatocellular carcinoma(HCC)patient subpopulation(s)can benefit from met-formin treatment.Here,through a genome-wide CRISPR-Cas9-based knockout screen,we find that DOCK1 levels determine the anti-tumor effects of met-formin and that DOCK1 is a synthetic lethal target of metformin in HCC.Mechanistically,metformin promotes DOCK1 phosphorylation,which activates RAC1 to facilitate cell survival,leading to metformin resistance.The DOCK1-selective inhibitor,TBOPP,potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids,and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models.Notably,metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression.This study shows that metformin effective-ness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for met-formin-resistant HCC patients.展开更多
高熵合金(HEA)不仅是有潜力的电化学析氧反应的催化剂,也可以用作电催化剂的载体.本文采用HF处理高熵合金使其羟基化(HF-HEA),然后再进行原位电化学活化,从而得到一种新型高效的CoCrFeNiAlHEA负载的Co,Fe,Ni-(O)OH电催化剂.该电催化剂仅...高熵合金(HEA)不仅是有潜力的电化学析氧反应的催化剂,也可以用作电催化剂的载体.本文采用HF处理高熵合金使其羟基化(HF-HEA),然后再进行原位电化学活化,从而得到一种新型高效的CoCrFeNiAlHEA负载的Co,Fe,Ni-(O)OH电催化剂.该电催化剂仅用240 m V超电势就可产生10 m A cm^-2的电流密度,Tafel斜率为52.7 m V dec^-1.本研究发现Cr和Al促进了HEA/Co,Fe,Ni-(O)OH的电化学活性.Cr和Al不仅增加了HF-HEA表面Ni(OH)x/Ni OOH的Ni^3+/Ni^2+摩尔比例,而且在电化学活化过程中Cr^3+和Al^3+的溶出增加了HF-HEA的电化学活性表面积.展开更多
Pancreaticβ-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes(T2D).Recent clinical and experimental studies have suggested that the functional capacity ofβ-cells,particularly in ...Pancreaticβ-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes(T2D).Recent clinical and experimental studies have suggested that the functional capacity ofβ-cells,particularly in the first phase of insulin secretion,is a primary contributor to the progression of T2D and its associated complications.Pancreaticβ-cells undergo dynamic compensation and decompensation processes during the development of T2D,in which metabolic stresses such as endoplasmic reticulum stress,oxidative stress,and inflammatory signals are key regulators ofβ-cell dynamics.Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D,especially in the early stages.Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague,accumulating evidence has implicated the improvement ofβ-cell functional capacity.In this review,we summarize recent advances in the understanding of the dynamic adaptations ofβ-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions onβ-cell dysfunction in T2D.This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D,and more importantly,it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.展开更多
Co_(3)O_(4)nanomaterials as electrodes have been studied widely in the past decade due to their unique structural characteristics.However,their performance does not yet reach the level required for practical applicati...Co_(3)O_(4)nanomaterials as electrodes have been studied widely in the past decade due to their unique structural characteristics.However,their performance does not yet reach the level required for practical applications.It is,nevertheless,an effective strategy to synthesize hybrid electrode materials with high energy density.Herein we prepare Co_(3)O_(4)@NiMoO_(4)nanowires by a two-step hydrothermal method.The as-obtained sample can be directly used as cathode material of supercapacitors;with specific capacitance of 600 C/g at 1 A/g.An assembled capacitor delivers an energy density of 36.1 Wh/kg at 2700 W/kg,and retains 98.2%of the initial capacity after 8000 cycles.展开更多
It is important to develop economical and durable electrocatalysts for sustainable energy conversion technology.However,the current catalysts still suffer from insufficient hydrogen adsorption energy.Herein,we report ...It is important to develop economical and durable electrocatalysts for sustainable energy conversion technology.However,the current catalysts still suffer from insufficient hydrogen adsorption energy.Herein,we report a kind of novel bi-phosphide catalyst through constructing heterogeneous structures and cation doping.The obtained sample delivers an outstanding hydrogen evolution reaction(HER)performance at all pH range.As oxygen evolution reaction(OER)electrocatalyst,Fe-CoP@Ni_(2)P samples show an overpotential of 237 mV at 50 mA·cm^(−2) in alkaline solution.For electrolysis of water,Fe-CoP@Ni_(2)P catalysts deliver a cell voltage of 1.59 V at 50 mA·cm^(−2) and long durability.Furthermore,density functional theory(DFT)calculation further confirms that the doped heterostructure promotes Gibbs free energy for hydrogen adsorption.And the significant increase in the density of total states(DOS)also enhances the catalytic activity of HER.展开更多
基金funded by the National Natural Science Foundation of China (32022006)Guangdong"Zhujiang’Innovation Teams (2019ZT08N628)+1 种基金the Agricultural Science and Technology Innovation Program (ASTIP) (CAASXTCX2016001)the special funds for science technology innovation and industrial development of Shenzhen Dapeng New District (PT202101-01).
文摘The garden pea(Pisum sativum L.)is a significant cool-season legume,serving as crucial food sources,animal feed,and industrial raw materials.The advancement of functional genomics over the past two decades has provided substantial theoretical foundations and progress to pea breeding.Notably,the release of the pea reference genome has enhanced our understanding of plant architecture,symbiotic nitrogen fixation(SNF),flowering time,floral organ development,seed development,and stress resistance.However,a considerable gap remains between pea functional genomics and molecular breeding.This review summarizes the current advancements in pea functional genomics and breeding while highlighting the future challenges in pea molecular breeding.
基金supported by National Natural Science Foundation of China(No.52172218)Key Laboratory of Engineering Dielectrics and Its Application(Harbin University of Science and Technology),Ministry of Education(No.KFZ202002)。
文摘Rational design of electrode meterials with unique core-shell nanostructures is of great significance for improving the electrochemical performance of supercapacitors. In this work, we prepare several CuCo_(2)O_(4)@Ni-Co-S composite electrodes by a controllable hydrothermal and electrodeposition route. Onedimensional nanowires can shorten the ions transport path, while two-dimensional nanosheets expose many active sites. This enables three-dimensional structured composite with high electrochemical activity. The as-prepared heterostructured materials show a specific of 1048 C/g at 1 A/g. It still maintains 75.6% of initial capacity after 20000 cycles at 10 A/g. The device delivers an energy density of 79.2 Wh/kg when the power density reaches to 2280 W/kg. Moreover, it possesses an excellent mechanical stability after repeated folding at different angles.
基金supported by the National Key Research and Development Program of China(2019YFA0111900,2022YFC3601900 and 2022YFC2505500)the National Natural Science Foundation of China(82261160397,82272560,81922017,92149306 and 82120108009)+5 种基金the NSFC/RGC Joint Research Schemethe Research Grants Council(UGC)of the Hong Kong Special Administrative Region and the National Natural Science Foundation of China(N_CUHK483/22)the Center for Neuromusculoskeletal Restorative Medicine by Innovation and Technology Commission(ITC)of Hong Kong SAR,China(CNRM at Inno HK),the National Institutes of Health(R61-AR073518 and R01-AR071930)the Key Research and Development Program of Hunan Province(2022SK2023)the Science and Technology Innovation Program of Hunan Province(2023RC1027,2022RC1009 and 2022RC3075)the Hunan Provincial Science and Technology Department(2023JJ30896)。
文摘Mechanical loading is required for bone homeostasis,but the underlying mechanism is still unclear.Our previous studies revealed that the mechanical protein polycystin-1(PC1,encoded by Pkd1)is critical for bone formation.However,the role of PC1 in bone resorption is unknown.Here,we found that PC1directly regulates osteoclastogenesis and bone resorption.The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts,decreased bone resorption,and increased bone mass.A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease,which is mainly caused by loss-of-function mutation of the PKD1 gene,is associated with a lower risk of hip fracture than those with other chronic kidney diseases.Moreover,mice with osteoclastspecific knockout of Pkd1 showed complete resistance to unloading-induced bone loss.A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass.Pharmacological regulation of the PC1-TAZ axis alleviated unloading-and estrogen deficiency-induced bone loss.Thus,the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.
基金National Natural Science Foundation of China(51521001,51832003)Fundamental Research Funds for the Central Universities(WUT:2019IB002)National College Students Innovation and Entrepreneurship Training Program(2019-C-B1-25).
文摘Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen production from water.Herein,we report a CoCrFeNiAl high-entropy alloy(HEA)electrocatalyst with self-supported structure synthesized by mechanical alloying and spark plasma sintering(SPS)consolidation.The HEA after HF treatment and in situ electrochemical activation for 4000 cycles of cyclic voltammetry(HF-HEAa2)presents favourable activity with overpotential of 73 mV to reach a current density of 10 mA cm^(2) and a Tafel slope of 39.7 mV dec1.The alloy effect of Al/Cr with Co/Fe/Ni at atomic level,high-temperature crystallization,as well as consolidation by SPS endow CoCrFeNiAl HEA with high stability in 0.5 M H2SO4 solution.The superior performance of HF-HEAa2 is related with the presence of metal hydroxides/oxides groups on HEA.
基金supported in part by National Key R&D Program of China(2018YFA0107103,2018YFA0800300)the Chinese Academy of Sciences(XDB39000000)+3 种基金National Natural Science Foundation of China(81930083,91957203,81821001,81525022)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110102001)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2017ZT07S054)the Fundamental Research Funds for the Central Universities(YD2070002008,2020ZYGXZR038).
文摘Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus remains unclear which hepatocellular carcinoma(HCC)patient subpopulation(s)can benefit from met-formin treatment.Here,through a genome-wide CRISPR-Cas9-based knockout screen,we find that DOCK1 levels determine the anti-tumor effects of met-formin and that DOCK1 is a synthetic lethal target of metformin in HCC.Mechanistically,metformin promotes DOCK1 phosphorylation,which activates RAC1 to facilitate cell survival,leading to metformin resistance.The DOCK1-selective inhibitor,TBOPP,potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids,and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models.Notably,metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression.This study shows that metformin effective-ness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for met-formin-resistant HCC patients.
基金financially supported by the National Natural Science Foundation of China(51521001 and 51832003)the Fundamental Research Funds for the Central Universities(WUT:2019IB002)the Students Innovation and Entrepreneurship Training Program(2019-C-B1-25)。
文摘高熵合金(HEA)不仅是有潜力的电化学析氧反应的催化剂,也可以用作电催化剂的载体.本文采用HF处理高熵合金使其羟基化(HF-HEA),然后再进行原位电化学活化,从而得到一种新型高效的CoCrFeNiAlHEA负载的Co,Fe,Ni-(O)OH电催化剂.该电催化剂仅用240 m V超电势就可产生10 m A cm^-2的电流密度,Tafel斜率为52.7 m V dec^-1.本研究发现Cr和Al促进了HEA/Co,Fe,Ni-(O)OH的电化学活性.Cr和Al不仅增加了HF-HEA表面Ni(OH)x/Ni OOH的Ni^3+/Ni^2+摩尔比例,而且在电化学活化过程中Cr^3+和Al^3+的溶出增加了HF-HEA的电化学活性表面积.
基金National Key Research and Development Programme of China(2018YFA0800403 and 2021YFC2701903)Training Program of the Major Research Plan of the National Natural Science Foundation of China(91857110)+6 种基金National Natural Science Fund for Excellent Young Scholars of China(81722012)National Natural Science Foundation of China(81670740)Zhejiang Provincial Natural Science Foundation of China(LZ21H070001)Innovative Institute of Basic Medical Sciences of Zhejiang University,the Fundamental Research Funds for the Central UniversitiesConstruction Fund of Medical Key Disciplines of Hangzhou(OO20200055)Hangzhou Science and Technology Bureau(20150733Q13 and ZD20200129)K.C.Wong Education Foundation.
文摘Pancreaticβ-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes(T2D).Recent clinical and experimental studies have suggested that the functional capacity ofβ-cells,particularly in the first phase of insulin secretion,is a primary contributor to the progression of T2D and its associated complications.Pancreaticβ-cells undergo dynamic compensation and decompensation processes during the development of T2D,in which metabolic stresses such as endoplasmic reticulum stress,oxidative stress,and inflammatory signals are key regulators ofβ-cell dynamics.Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D,especially in the early stages.Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague,accumulating evidence has implicated the improvement ofβ-cell functional capacity.In this review,we summarize recent advances in the understanding of the dynamic adaptations ofβ-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions onβ-cell dysfunction in T2D.This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D,and more importantly,it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.
基金This project was supported by the Natural National Science Foundation of China(Grant No.52172218)the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2019W-NLOKF017).
文摘Co_(3)O_(4)nanomaterials as electrodes have been studied widely in the past decade due to their unique structural characteristics.However,their performance does not yet reach the level required for practical applications.It is,nevertheless,an effective strategy to synthesize hybrid electrode materials with high energy density.Herein we prepare Co_(3)O_(4)@NiMoO_(4)nanowires by a two-step hydrothermal method.The as-obtained sample can be directly used as cathode material of supercapacitors;with specific capacitance of 600 C/g at 1 A/g.An assembled capacitor delivers an energy density of 36.1 Wh/kg at 2700 W/kg,and retains 98.2%of the initial capacity after 8000 cycles.
基金supported by the National Natural Science Foundation of China(No.52172218).
文摘It is important to develop economical and durable electrocatalysts for sustainable energy conversion technology.However,the current catalysts still suffer from insufficient hydrogen adsorption energy.Herein,we report a kind of novel bi-phosphide catalyst through constructing heterogeneous structures and cation doping.The obtained sample delivers an outstanding hydrogen evolution reaction(HER)performance at all pH range.As oxygen evolution reaction(OER)electrocatalyst,Fe-CoP@Ni_(2)P samples show an overpotential of 237 mV at 50 mA·cm^(−2) in alkaline solution.For electrolysis of water,Fe-CoP@Ni_(2)P catalysts deliver a cell voltage of 1.59 V at 50 mA·cm^(−2) and long durability.Furthermore,density functional theory(DFT)calculation further confirms that the doped heterostructure promotes Gibbs free energy for hydrogen adsorption.And the significant increase in the density of total states(DOS)also enhances the catalytic activity of HER.