目的:探讨RNA m^(6)A甲基化修饰在脂肪细胞胰岛素抵抗中的作用及机制。方法:收集2型糖尿病患者术中赘余皮下脂肪组织,以非2型糖尿病患者同样组织为对照,检测组间RNA m^(6)A水平。高脂饮食诱导C57BL/6J小鼠构建胰岛素抵抗(in⁃sulin resis...目的:探讨RNA m^(6)A甲基化修饰在脂肪细胞胰岛素抵抗中的作用及机制。方法:收集2型糖尿病患者术中赘余皮下脂肪组织,以非2型糖尿病患者同样组织为对照,检测组间RNA m^(6)A水平。高脂饮食诱导C57BL/6J小鼠构建胰岛素抵抗(in⁃sulin resistance,IR)模型(HFD组,n=5,60%高脂饲料喂养16周),对照组10%低脂饲料喂养16周(CD组,n=5)。模型构建成功后,取附睾周围脂肪组织行表观转录组学m^(6)A甲基化修饰芯片检测,并借助MeRIP-qPCR实验、RT-qPCR以及RNA结合蛋白免疫沉淀测定(RNA Binding Protein Immunoprecipitation Assay,RIP)实验验证胰岛素信号转导相关基因变化;进一步观察METTL3小分子抑制剂STM2457对高脂饮食诱导下小鼠胰岛素信号转导基因的影响。结果:2型糖尿病患者和小鼠IR模型脂肪组织中总体m^(6)A修饰水平均升高(患者200 ng RNA t=-8.375,P<0.001;患者100 ng RNA t=-3.722,P=0.006;患者50 ng RNA t=-4.937;P=0.001;小鼠100 ng RNA t=-3.590,P=0.023;小鼠50 ng RNA t=-2.760,P=0.025)。表观转录组学检测证实IR的脂肪组织中1175个基因发生高m^(6)A修饰,55个基因发生低m^(6)A修饰,同时有182个基因呈现高m^(6)A修饰且低表达,包括AKT2、INSR、PIK3R1、ACACA、SREBF1等5个胰岛素信号转导关键基因,其中AKT2、INSR、ACACA、SREBF1等4个基因被确证并证实其与METTL3存在直接结合,其m^(6)A修饰水平受METTL3正向调控。STM2457作用下,胰岛素敏感性提高,且AKT2、INSR、ACACA、SREBF1转录水平上调,提示IR表型改善明显。结论:高脂饮食通过METTL3诱导脂肪细胞胰岛素信号转导基因AKT2、INSR、ACACA、SREBF1发生m^(6)A高甲基化修饰,诱导其低表达,阻滞胰岛素信号转导,进而参与诱发IR。展开更多
Magnesium(Mg)alloys have shown great prospects as both structural and biomedical materials,while poor corrosion resistance limits their further application.In this work,to avoid the time-consuming and laborious experi...Magnesium(Mg)alloys have shown great prospects as both structural and biomedical materials,while poor corrosion resistance limits their further application.In this work,to avoid the time-consuming and laborious experiment trial,a high-throughput computational strategy based on first-principles calculations is designed for screening corrosion-resistant binary Mg alloy with intermetallics,from both the thermodynamic and kinetic perspectives.The stable binary Mg intermetallics with low equilibrium potential difference with respect to the Mg matrix are firstly identified.Then,the hydrogen adsorption energies on the surfaces of these Mg intermetallics are calculated,and the corrosion exchange current density is further calculated by a hydrogen evolution reaction(HER)kinetic model.Several intermetallics,e.g.Y_(3)Mg,Y_(2)Mg and La_(5)Mg,are identified to be promising intermetallics which might effectively hinder the cathodic HER.Furthermore,machine learning(ML)models are developed to predict Mg intermetallics with proper hydrogen adsorption energy employing work function(W_(f))and weighted first ionization energy(WFIE).The generalization of the ML models is tested on five new binary Mg intermetallics with the average root mean square error(RMSE)of 0.11 eV.This study not only predicts some promising binary Mg intermetallics which may suppress the galvanic corrosion,but also provides a high-throughput screening strategy and ML models for the design of corrosion-resistant alloy,which can be extended to ternary Mg alloys or other alloy systems.展开更多
This work studied the microstructure,mechanical properties and damping properties of Mg_(95.34)Ni_(2)Y_(2.66) and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys systematically.The difference in the evolution of the long-period ...This work studied the microstructure,mechanical properties and damping properties of Mg_(95.34)Ni_(2)Y_(2.66) and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys systematically.The difference in the evolution of the long-period stacked ordered(LPSO)phase in the two alloys during heat treatment was the focus.The morphology of the as-cast Mg_(95.34)Ni_(2)Y_(2.66)presented a disordered network.After heat treatment at 773 K for 2 hours,the eutectic phase was integrated into the matrix,and the LPSO phase maintained the 18R structure.As Zn partially replaced Ni,the crystal grains became rounded in the cast alloy,and lamellar LPSO phases and more solid solution atoms were contained in the matrix after heat treatment of the Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloy.Both Zn and the heat treatment had a significant effect on damping.Obvious dislocation internal friction peaks and grain boundary internal friction peaks were found after temperature-dependent damping of the Mg_(95.34)Ni_(2)Y_(2.66)and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys.After heat treatment,the dislocation peak was significantly increased,especially in the alloy Mg_(95.34)Ni_(2)Y_(2).66.The annealed Mg_(95.34)Ni_(2)Y_(2.66)alloy with a rod-shaped LPSO phase exhibited a good damping performance of 0.14 atε=10^(−3),which was due to the difference between the second phase and solid solution atom content.These factors also affected the dynamic modulus of the alloy.The results of this study will help in further development of high-damping magnesium alloys.展开更多
In recent years,the exploration of seabed has been intensified,but the submarine soils of silt and sand in the Yellow Sea area have not been well investigated so far.In this study,the physical and mechanical propertie...In recent years,the exploration of seabed has been intensified,but the submarine soils of silt and sand in the Yellow Sea area have not been well investigated so far.In this study,the physical and mechanical properties of silt and sand from the Yellow Sea were measured using a direct shear apparatus and their microstructures were observed using a scanning electron microscope.The test results suggest that the shear strength of silt and sand increases linearly with the increase of normal stress.Based on the direct shear test,the scanning electron microscope was used to observe the section surface of sand.It is observed that the section surface becomes rough,with many“V”‐shaped cracks.Many particles appear on the surface of the silt structure and tend to be disintegrated.The X‐ray diffraction experiment reveals that the sand and silt have different compositions.The shear strength of sand is slightly greater than that of silt under high stress,which is related to the shape of soil particles and the mineral composition.These results can be a reference for further study of other soils in the Yellow Sea;meanwhile,they can serve as soil parameters for the stability and durability analyses of offshore infrastructure construction.展开更多
The construction of extraterrestrial bases has become a new goal in the active exploration of deep space.Among the construction techniques,in situ resource-based construction is one of the most promising because of it...The construction of extraterrestrial bases has become a new goal in the active exploration of deep space.Among the construction techniques,in situ resource-based construction is one of the most promising because of its good sustainability and acceptable economic cost,triggering the development of various types of extraterrestrial construction materials.A comprehensive survey and comparison of materials from the perspective of performance was conducted to provide suggestions for material selection and optimization.Thirteen types of typical construction materials are discussed in terms of their reliability and applicability in extreme extraterrestrial environment.Mechanical,thermal and optical,and radiation-shielding properties are considered.The influencing factors and optimization methods for these properties are analyzed.From the perspective of material properties,the existing challenges lie in the comprehensive,long-term,and real characterization of regolith-based construction materials.Correspondingly,the suggested future directions include the application of high-throughput characterization methods,accelerated durability tests,and conducting extraterrestrial experiments.展开更多
The purpose of this research is to investigate the hydration behavior and cementitious properties of the mixture of calcium carbonate and aluminate, and to explore whether it can be adopted as a new low-carbon cementi...The purpose of this research is to investigate the hydration behavior and cementitious properties of the mixture of calcium carbonate and aluminate, and to explore whether it can be adopted as a new low-carbon cementitious material. The composite system of calcium carbonate and aluminate minerals is studied by measuring the component of hydration products, the hydration heat, setting time and compressive strength.The results prove that the composite system has certain cementitious properties and is feasible to prepare new low-carbon cement.展开更多
文摘目的:探讨RNA m^(6)A甲基化修饰在脂肪细胞胰岛素抵抗中的作用及机制。方法:收集2型糖尿病患者术中赘余皮下脂肪组织,以非2型糖尿病患者同样组织为对照,检测组间RNA m^(6)A水平。高脂饮食诱导C57BL/6J小鼠构建胰岛素抵抗(in⁃sulin resistance,IR)模型(HFD组,n=5,60%高脂饲料喂养16周),对照组10%低脂饲料喂养16周(CD组,n=5)。模型构建成功后,取附睾周围脂肪组织行表观转录组学m^(6)A甲基化修饰芯片检测,并借助MeRIP-qPCR实验、RT-qPCR以及RNA结合蛋白免疫沉淀测定(RNA Binding Protein Immunoprecipitation Assay,RIP)实验验证胰岛素信号转导相关基因变化;进一步观察METTL3小分子抑制剂STM2457对高脂饮食诱导下小鼠胰岛素信号转导基因的影响。结果:2型糖尿病患者和小鼠IR模型脂肪组织中总体m^(6)A修饰水平均升高(患者200 ng RNA t=-8.375,P<0.001;患者100 ng RNA t=-3.722,P=0.006;患者50 ng RNA t=-4.937;P=0.001;小鼠100 ng RNA t=-3.590,P=0.023;小鼠50 ng RNA t=-2.760,P=0.025)。表观转录组学检测证实IR的脂肪组织中1175个基因发生高m^(6)A修饰,55个基因发生低m^(6)A修饰,同时有182个基因呈现高m^(6)A修饰且低表达,包括AKT2、INSR、PIK3R1、ACACA、SREBF1等5个胰岛素信号转导关键基因,其中AKT2、INSR、ACACA、SREBF1等4个基因被确证并证实其与METTL3存在直接结合,其m^(6)A修饰水平受METTL3正向调控。STM2457作用下,胰岛素敏感性提高,且AKT2、INSR、ACACA、SREBF1转录水平上调,提示IR表型改善明显。结论:高脂饮食通过METTL3诱导脂肪细胞胰岛素信号转导基因AKT2、INSR、ACACA、SREBF1发生m^(6)A高甲基化修饰,诱导其低表达,阻滞胰岛素信号转导,进而参与诱发IR。
基金financially supported by the National Key Research and Development Program of China(No.2016YFB0701202,No.2017YFB0701500 and No.2020YFB1505901)National Natural Science Foundation of China(General Program No.51474149,52072240)+3 种基金Shanghai Science and Technology Committee(No.18511109300)Science and Technology Commission of the CMC(2019JCJQZD27300)financial support from the University of Michigan and Shanghai Jiao Tong University joint funding,China(AE604401)Science and Technology Commission of Shanghai Municipality(No.18511109302).
文摘Magnesium(Mg)alloys have shown great prospects as both structural and biomedical materials,while poor corrosion resistance limits their further application.In this work,to avoid the time-consuming and laborious experiment trial,a high-throughput computational strategy based on first-principles calculations is designed for screening corrosion-resistant binary Mg alloy with intermetallics,from both the thermodynamic and kinetic perspectives.The stable binary Mg intermetallics with low equilibrium potential difference with respect to the Mg matrix are firstly identified.Then,the hydrogen adsorption energies on the surfaces of these Mg intermetallics are calculated,and the corrosion exchange current density is further calculated by a hydrogen evolution reaction(HER)kinetic model.Several intermetallics,e.g.Y_(3)Mg,Y_(2)Mg and La_(5)Mg,are identified to be promising intermetallics which might effectively hinder the cathodic HER.Furthermore,machine learning(ML)models are developed to predict Mg intermetallics with proper hydrogen adsorption energy employing work function(W_(f))and weighted first ionization energy(WFIE).The generalization of the ML models is tested on five new binary Mg intermetallics with the average root mean square error(RMSE)of 0.11 eV.This study not only predicts some promising binary Mg intermetallics which may suppress the galvanic corrosion,but also provides a high-throughput screening strategy and ML models for the design of corrosion-resistant alloy,which can be extended to ternary Mg alloys or other alloy systems.
基金funded by the National Natural Science Foundation of China(Nos.51801189)The Central Guidance on Local Science and Technology Development Fund of Shanxi Province(Nos.YDZJTSX2021A027)+2 种基金The National Natural Science Foundation of China(Nos.51801189)The Science and Technology Major Project of Shanxi Province(No.20191102008,20191102007)The North University of China Youth Academic Leader Project(No.11045505).
文摘This work studied the microstructure,mechanical properties and damping properties of Mg_(95.34)Ni_(2)Y_(2.66) and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys systematically.The difference in the evolution of the long-period stacked ordered(LPSO)phase in the two alloys during heat treatment was the focus.The morphology of the as-cast Mg_(95.34)Ni_(2)Y_(2.66)presented a disordered network.After heat treatment at 773 K for 2 hours,the eutectic phase was integrated into the matrix,and the LPSO phase maintained the 18R structure.As Zn partially replaced Ni,the crystal grains became rounded in the cast alloy,and lamellar LPSO phases and more solid solution atoms were contained in the matrix after heat treatment of the Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloy.Both Zn and the heat treatment had a significant effect on damping.Obvious dislocation internal friction peaks and grain boundary internal friction peaks were found after temperature-dependent damping of the Mg_(95.34)Ni_(2)Y_(2.66)and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys.After heat treatment,the dislocation peak was significantly increased,especially in the alloy Mg_(95.34)Ni_(2)Y_(2).66.The annealed Mg_(95.34)Ni_(2)Y_(2.66)alloy with a rod-shaped LPSO phase exhibited a good damping performance of 0.14 atε=10^(−3),which was due to the difference between the second phase and solid solution atom content.These factors also affected the dynamic modulus of the alloy.The results of this study will help in further development of high-damping magnesium alloys.
基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20210527National Natural Science Foundation of China,Grant/Award Number:42107158Training Program for Innovation and Entrepreneurship,China University of Mining and Technology。
文摘In recent years,the exploration of seabed has been intensified,but the submarine soils of silt and sand in the Yellow Sea area have not been well investigated so far.In this study,the physical and mechanical properties of silt and sand from the Yellow Sea were measured using a direct shear apparatus and their microstructures were observed using a scanning electron microscope.The test results suggest that the shear strength of silt and sand increases linearly with the increase of normal stress.Based on the direct shear test,the scanning electron microscope was used to observe the section surface of sand.It is observed that the section surface becomes rough,with many“V”‐shaped cracks.Many particles appear on the surface of the silt structure and tend to be disintegrated.The X‐ray diffraction experiment reveals that the sand and silt have different compositions.The shear strength of sand is slightly greater than that of silt under high stress,which is related to the shape of soil particles and the mineral composition.These results can be a reference for further study of other soils in the Yellow Sea;meanwhile,they can serve as soil parameters for the stability and durability analyses of offshore infrastructure construction.
基金supported by the National Key Research and Development Program of China(2023YFB3711300 and 2021YFF0500300)the Strategic Research and Consulting Project of the Chinese Academy of Engineering(2023-XZ-90 and 2023-JB-09-10)the National Key Research and Development Program of China(2021YFF0500300).
文摘The construction of extraterrestrial bases has become a new goal in the active exploration of deep space.Among the construction techniques,in situ resource-based construction is one of the most promising because of its good sustainability and acceptable economic cost,triggering the development of various types of extraterrestrial construction materials.A comprehensive survey and comparison of materials from the perspective of performance was conducted to provide suggestions for material selection and optimization.Thirteen types of typical construction materials are discussed in terms of their reliability and applicability in extreme extraterrestrial environment.Mechanical,thermal and optical,and radiation-shielding properties are considered.The influencing factors and optimization methods for these properties are analyzed.From the perspective of material properties,the existing challenges lie in the comprehensive,long-term,and real characterization of regolith-based construction materials.Correspondingly,the suggested future directions include the application of high-throughput characterization methods,accelerated durability tests,and conducting extraterrestrial experiments.
基金Funded by the National Natural Science Foundation of China (Nos.51772033, 52002040)the National Key Research and Development Program of China (No. 2023YFB3711400)。
文摘The purpose of this research is to investigate the hydration behavior and cementitious properties of the mixture of calcium carbonate and aluminate, and to explore whether it can be adopted as a new low-carbon cementitious material. The composite system of calcium carbonate and aluminate minerals is studied by measuring the component of hydration products, the hydration heat, setting time and compressive strength.The results prove that the composite system has certain cementitious properties and is feasible to prepare new low-carbon cement.
