Polymers often exhibit multi-state conformational transitions with multiple pathways as temperature varies.However,characterizing the inherent features of these pathways is hindered by the lack of physical characteriz...Polymers often exhibit multi-state conformational transitions with multiple pathways as temperature varies.However,characterizing the inherent features of these pathways is hindered by the lack of physical characterizations that can distinguish various transition pathways between complex and disordered states.In this work,we introduced a machine-learning framework based on spatiotemporal point-cloud neural networks to identify and analyze conformational transition pathways in polymer chains.As a case study,we applied this framework to the temperature-induced unfolding of a single semi-flexible polymer chain,simulated via coarse-grained molecular dynamics.We first combined spatiotemporal point cloud neural networks and contrastive learning to extract features of conformational evolution,and then we employed unsupervised learning methods to cluster distinct transition pathways and unfolding trajectories.Our results reveal that,with increasing temperature,semi-flexible polymer chains exhibit five distinct unfolding pathways:rigid rod→random coil;small toroid→large toroid→hairpin→random coil;rod bundle→hairpin→random coil;hairpin→random coil;and tailed structure→random coil.We further calculated the structural order parameters of those typical conformations with distinct transition pathways,we distincted five transition mechanisms,including the straightening of rigid rods,tightening of small rings,expansion of hairpin ends,symmetrization of rod bundles,and retraction of tailed structures.These findings demonstrate that our framework presents a promising data-driven approach for analyzing complex conformational transitions in disordered polymers,which might be potentially extendable to other heterogeneous systems like intrinsically disordered proteins.展开更多
As the world's biggest carbon dioxide(CO_(2))emitter and the largest developing country,China faces daunting challenges to peak its emissions before 2030 and achieve carbon neutrality within 40 years.This study fu...As the world's biggest carbon dioxide(CO_(2))emitter and the largest developing country,China faces daunting challenges to peak its emissions before 2030 and achieve carbon neutrality within 40 years.This study fully considered the carbon-neutrality goal and the temperature rise constraints required by the Paris Agreement,by developing six long-term development scenarios,and conducting a quantitative evaluation on the carbon emissions pathways,energy transformation,technology,policy and investment demand for each scenario.This study combined both bottom-up and top-down methodologies,including simulations and analyses of energy consumption of end-use and power sectors(bottom-up),as well as scenario analysis,investment demand and technology evaluation at the macro level(top-down).This study demonstrates that achieving carbon neutrality before 2060 translates to significant efforts and overwhelming challenges for China.To comply with the target,a high rate of an average annual reduction of CO_(2) emissions by 9.3%from 2030 to 2050 is a necessity,which requires a huge investment demand.For example,in the 1.5℃ scenario,an investment in energy infrastructure alone equivalent to 2.6%of that year's GDP will be necessary.The technological pathway towards carbon neutrality will rely highly on both conventional emission reduction technologies and breakthrough technologies.China needs to balance a long-term development strategy of lower greenhouse gas emissions that meets both the Paris Agreement and the long-term goals for domestic economic and social development,with a phased implementation for both its five-year and long-term plans.展开更多
When two distinct ordered phases contact,the interface may exhibit rich and fascinating structures.Focusing on the Cylinder-Gyroid interface system,transition pathways connecting various interface morphologies are stu...When two distinct ordered phases contact,the interface may exhibit rich and fascinating structures.Focusing on the Cylinder-Gyroid interface system,transition pathways connecting various interface morphologies are studied armed with the Landau–Brazovskii model.Specifically,minimum energy paths are obtained by computing transition states with the saddle dynamics.We present four primary transition pathways connecting different local minima,representing four different mechanisms of the formation of the Cylinder-Gyroid interface.The connection of Cylinder and Gyroid can be either direct or indirect via Fddd with three different orientations.Under different displacements,each of the four pathways may have the lowest energy.展开更多
BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role o...BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role of MEX3A in hepatocellular carcinoma(HCC)remains largely unexplored,with limited reports available in the literature.AIM To investigate expression and clinical significance of MEX3A in HCC and explore its potential role in tumor progression.METHODS We analyzed MEX3A mRNA expression in HCC and adjacent tissues using data from The Cancer Genome Atlas(TCGA).The correlation between MEX3A expression and overall survival(OS)was evaluated.Immunohistochemistry was performed on HCC surgical specimens to validate MEX3A expression and its association with clinical parameters,including hepatitis B virus(HBV)positivity,tumor differentiation and tumor size.Additionally,MEX3A knockdown HCC cell lines were constructed to explore the biological functions of MEX3A.Cell prolif-eration was assessed using cell counting kit-8 and clone formation assays,while cell cycle progression was analyzed by flow cytometry.The effects of MEX3A on the Wnt/β-catenin signaling pathway were examined by western blotting and immunofluorescence.Cell migration was evaluated using scratch and Transwell assays.Finally,the role of the transcription factor RORA in mediating MEX3A effects was explored by silencing RORA and analyzing its impact on cell proliferation and protein expression.RESULTS TCGA data analysis revealed that MEX3A mRNA expression was significantly higher in HCC tissues compared to adjacent tissues.Higher MEX3A expression was associated with poorer OS.These findings were validated in HCC surgical specimens.Immunohistochemistry confirmed elevated MEX3A expression in HCC tissues and showed positive correlations with Ki-67 and vimentin levels.MEX3A expression was closely related to HBV positivity,tumor differentiation and tumor size.Mechanistic studies demonstrated that MEX3A knockdown inhibited cell proliferation and cell cycle progression,as shown by reduced expression ofβ-catenin,c-Myc and cyclin D1.Additionally,MEX3A knockdown inhibited the nuclear entry ofβ-catenin,thereby suppressing the activation of downstream oncogenic pathways.MEX3A depletion significantly reduced the migratory ability of HCC cells,likely through downregulation of the epithelial-mesenchymal transition pathway.Transcription factor analysis identified RORA as a potential mediator of MEX3A effects.Silencing RORA antagonized the effects of MEX3A on cell proliferation and the expression ofβ-catenin,c-Myc and cyclin D1.CONCLUSION MEX3A promotes cell proliferation in HCC by regulating the RORA/β-catenin pathway.Our findings suggest that MEX3A could serve as a prognostic marker and therapeutic target for HCC.展开更多
The energy sector has an essential role in limiting the global average temperature increase to below 2°C.Redirecting and advancing technological progress contribute to carbon-free transition solutions.Energy tran...The energy sector has an essential role in limiting the global average temperature increase to below 2°C.Redirecting and advancing technological progress contribute to carbon-free transition solutions.Energy transition is currently one of the most debated issues in the world.This paper reviews and summarizes the current policy projections and their assumptions organized by some major countries in the energy sector,particularly in the coal sector,and provides a detailed discussion on specific and significant socio-technical pathways taken by countries to achieve zero-carbon targets.Their implementation involves restructuring the existing energy system and requires appropriate policy support and sufficient investment in infrastructure development and technological innovation.Some basic principles and countermeasures that have already been implemented by some major emitters,such as India and China,are also discussed,with different transformation pathways.Critical suggestions are also provided,such as implementing best practice policies at the national level,moving to more efficient transition strategies,national and regional cooperation,cross-border energy grid integration,and private sector involvement to reduce carbon emissions from coal-fired power plants,not only by reducing coal consumption but also by introducing various low carbon technologies.展开更多
The endothelial-to-mesenchymal transition（End MT） in endothelial cells contributes to the development of cardiac fibrosis,ultimately leading to cardiac remodeling.In this study,the effects and molecular mechanisms o...The endothelial-to-mesenchymal transition（End MT） in endothelial cells contributes to the development of cardiac fibrosis,ultimately leading to cardiac remodeling.In this study,the effects and molecular mechanisms of celastrol（CEL） on transforming growth factor-β1（TGF-β1）-induced End MT in human umbilical vein endothelial（HUVEC-12） cells were investigated.The presented data demonstrated that CEL significantly blocked the morphology change of HUVEC-12 cells induced by TGF-β1 without cell cytotoxicity.In accordance with these findings,CEL blocked TGF-β1-induced EndM T as evidenced by the inhibition of the mesenchymal markers,including collagen Ⅰ,Ⅲ,α-SMA,fibronectin m RNA expression,and the increase in the m RNA expression of endothelial cell marker CD31.These changes were also confirmed by double immunofluorescence staining of CD31 and vimentin.The in vitro scratch assay showed that CEL inhibited the migration capacity of the transitioned endothelial cells induced by TGF-β1.Further experiments showed that the beneficial effect of CEL on blocking the End MT in HUVEC-12 cells was associated with the suppression of the TGF-β1/Smads signalling pathway,which was also confirmed by the inhibition of its downstream transcription factor snail1,twist1,twist2,ZEB1 and ZEB2.These results indicate that CEL blocks TGF-β1-induced End MT through TGF-β1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases.展开更多
Photocatalysis opens unique pathways for reductive hydrogenation under mild conditions.Typically,photocatalytic hydrogenation proceeds via single electron transfer(SET),followed by hydrogen atom transfer.Herein,we elu...Photocatalysis opens unique pathways for reductive hydrogenation under mild conditions.Typically,photocatalytic hydrogenation proceeds via single electron transfer(SET),followed by hydrogen atom transfer.Herein,we elucidate that the deliberate arrangement of an electron reservoir and Ni catalysts enables a transition from photoinduced one-to twoelectron transfer,yielding desired products via proton acquisition.Specifically,arranging carbon nitride(CN)that stores multiple photogenerated electrons in proximity to a chemically bonded Ni site accomplishes competitive two-electron/proton hydrogenation of halogenated substrates using water as the hydrogen source,outperforming the SETmediated process.In contrast,the nonchemically bonded Ni and CN system exhibits poor activity for 2e−/H+hydrogenation.Mechanistic studies further reveal that the low-valent Ni+and CN(e−)cooperate to transfer two electrons to the substrate.The catalytic utility of this two-electron mechanism is further underscored by the deuterium labeling of diverse(hetero)arenes and bioactive molecules in D_(2)O,achieving deuterium incorporation of up to 99%.Our work highlights the value of light-driven multipleelectron catalysis that reaches otherwise challenging transformations.展开更多
基金financially supported by the National Key R&D Program of China(No.2022YFB3707303)the National Natural Science Foundation of China(No.52293471)。
文摘Polymers often exhibit multi-state conformational transitions with multiple pathways as temperature varies.However,characterizing the inherent features of these pathways is hindered by the lack of physical characterizations that can distinguish various transition pathways between complex and disordered states.In this work,we introduced a machine-learning framework based on spatiotemporal point-cloud neural networks to identify and analyze conformational transition pathways in polymer chains.As a case study,we applied this framework to the temperature-induced unfolding of a single semi-flexible polymer chain,simulated via coarse-grained molecular dynamics.We first combined spatiotemporal point cloud neural networks and contrastive learning to extract features of conformational evolution,and then we employed unsupervised learning methods to cluster distinct transition pathways and unfolding trajectories.Our results reveal that,with increasing temperature,semi-flexible polymer chains exhibit five distinct unfolding pathways:rigid rod→random coil;small toroid→large toroid→hairpin→random coil;rod bundle→hairpin→random coil;hairpin→random coil;and tailed structure→random coil.We further calculated the structural order parameters of those typical conformations with distinct transition pathways,we distincted five transition mechanisms,including the straightening of rigid rods,tightening of small rings,expansion of hairpin ends,symmetrization of rod bundles,and retraction of tailed structures.These findings demonstrate that our framework presents a promising data-driven approach for analyzing complex conformational transitions in disordered polymers,which might be potentially extendable to other heterogeneous systems like intrinsically disordered proteins.
文摘As the world's biggest carbon dioxide(CO_(2))emitter and the largest developing country,China faces daunting challenges to peak its emissions before 2030 and achieve carbon neutrality within 40 years.This study fully considered the carbon-neutrality goal and the temperature rise constraints required by the Paris Agreement,by developing six long-term development scenarios,and conducting a quantitative evaluation on the carbon emissions pathways,energy transformation,technology,policy and investment demand for each scenario.This study combined both bottom-up and top-down methodologies,including simulations and analyses of energy consumption of end-use and power sectors(bottom-up),as well as scenario analysis,investment demand and technology evaluation at the macro level(top-down).This study demonstrates that achieving carbon neutrality before 2060 translates to significant efforts and overwhelming challenges for China.To comply with the target,a high rate of an average annual reduction of CO_(2) emissions by 9.3%from 2030 to 2050 is a necessity,which requires a huge investment demand.For example,in the 1.5℃ scenario,an investment in energy infrastructure alone equivalent to 2.6%of that year's GDP will be necessary.The technological pathway towards carbon neutrality will rely highly on both conventional emission reduction technologies and breakthrough technologies.China needs to balance a long-term development strategy of lower greenhouse gas emissions that meets both the Paris Agreement and the long-term goals for domestic economic and social development,with a phased implementation for both its five-year and long-term plans.
基金supported by the National Natural Science Foundation of China No.12001524 and and No.12288201supported by the National Natural Science Foundation of China No.12050002 and the National Key R&D Program of China 2021YFF1200500.
文摘When two distinct ordered phases contact,the interface may exhibit rich and fascinating structures.Focusing on the Cylinder-Gyroid interface system,transition pathways connecting various interface morphologies are studied armed with the Landau–Brazovskii model.Specifically,minimum energy paths are obtained by computing transition states with the saddle dynamics.We present four primary transition pathways connecting different local minima,representing four different mechanisms of the formation of the Cylinder-Gyroid interface.The connection of Cylinder and Gyroid can be either direct or indirect via Fddd with three different orientations.Under different displacements,each of the four pathways may have the lowest energy.
基金Supported by Suzhou Municipal Science and Technology Bureau,No.SYS2020081.
文摘BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role of MEX3A in hepatocellular carcinoma(HCC)remains largely unexplored,with limited reports available in the literature.AIM To investigate expression and clinical significance of MEX3A in HCC and explore its potential role in tumor progression.METHODS We analyzed MEX3A mRNA expression in HCC and adjacent tissues using data from The Cancer Genome Atlas(TCGA).The correlation between MEX3A expression and overall survival(OS)was evaluated.Immunohistochemistry was performed on HCC surgical specimens to validate MEX3A expression and its association with clinical parameters,including hepatitis B virus(HBV)positivity,tumor differentiation and tumor size.Additionally,MEX3A knockdown HCC cell lines were constructed to explore the biological functions of MEX3A.Cell prolif-eration was assessed using cell counting kit-8 and clone formation assays,while cell cycle progression was analyzed by flow cytometry.The effects of MEX3A on the Wnt/β-catenin signaling pathway were examined by western blotting and immunofluorescence.Cell migration was evaluated using scratch and Transwell assays.Finally,the role of the transcription factor RORA in mediating MEX3A effects was explored by silencing RORA and analyzing its impact on cell proliferation and protein expression.RESULTS TCGA data analysis revealed that MEX3A mRNA expression was significantly higher in HCC tissues compared to adjacent tissues.Higher MEX3A expression was associated with poorer OS.These findings were validated in HCC surgical specimens.Immunohistochemistry confirmed elevated MEX3A expression in HCC tissues and showed positive correlations with Ki-67 and vimentin levels.MEX3A expression was closely related to HBV positivity,tumor differentiation and tumor size.Mechanistic studies demonstrated that MEX3A knockdown inhibited cell proliferation and cell cycle progression,as shown by reduced expression ofβ-catenin,c-Myc and cyclin D1.Additionally,MEX3A knockdown inhibited the nuclear entry ofβ-catenin,thereby suppressing the activation of downstream oncogenic pathways.MEX3A depletion significantly reduced the migratory ability of HCC cells,likely through downregulation of the epithelial-mesenchymal transition pathway.Transcription factor analysis identified RORA as a potential mediator of MEX3A effects.Silencing RORA antagonized the effects of MEX3A on cell proliferation and the expression ofβ-catenin,c-Myc and cyclin D1.CONCLUSION MEX3A promotes cell proliferation in HCC by regulating the RORA/β-catenin pathway.Our findings suggest that MEX3A could serve as a prognostic marker and therapeutic target for HCC.
基金Global Energy Internet Group Co.,Ltd Science and Technology Project(SGGEIG00JYJS2000046)by National Natural Science Foundation of China(51977123).
文摘The energy sector has an essential role in limiting the global average temperature increase to below 2°C.Redirecting and advancing technological progress contribute to carbon-free transition solutions.Energy transition is currently one of the most debated issues in the world.This paper reviews and summarizes the current policy projections and their assumptions organized by some major countries in the energy sector,particularly in the coal sector,and provides a detailed discussion on specific and significant socio-technical pathways taken by countries to achieve zero-carbon targets.Their implementation involves restructuring the existing energy system and requires appropriate policy support and sufficient investment in infrastructure development and technological innovation.Some basic principles and countermeasures that have already been implemented by some major emitters,such as India and China,are also discussed,with different transformation pathways.Critical suggestions are also provided,such as implementing best practice policies at the national level,moving to more efficient transition strategies,national and regional cooperation,cross-border energy grid integration,and private sector involvement to reduce carbon emissions from coal-fired power plants,not only by reducing coal consumption but also by introducing various low carbon technologies.
文摘The endothelial-to-mesenchymal transition（End MT） in endothelial cells contributes to the development of cardiac fibrosis,ultimately leading to cardiac remodeling.In this study,the effects and molecular mechanisms of celastrol（CEL） on transforming growth factor-β1（TGF-β1）-induced End MT in human umbilical vein endothelial（HUVEC-12） cells were investigated.The presented data demonstrated that CEL significantly blocked the morphology change of HUVEC-12 cells induced by TGF-β1 without cell cytotoxicity.In accordance with these findings,CEL blocked TGF-β1-induced EndM T as evidenced by the inhibition of the mesenchymal markers,including collagen Ⅰ,Ⅲ,α-SMA,fibronectin m RNA expression,and the increase in the m RNA expression of endothelial cell marker CD31.These changes were also confirmed by double immunofluorescence staining of CD31 and vimentin.The in vitro scratch assay showed that CEL inhibited the migration capacity of the transitioned endothelial cells induced by TGF-β1.Further experiments showed that the beneficial effect of CEL on blocking the End MT in HUVEC-12 cells was associated with the suppression of the TGF-β1/Smads signalling pathway,which was also confirmed by the inhibition of its downstream transcription factor snail1,twist1,twist2,ZEB1 and ZEB2.These results indicate that CEL blocks TGF-β1-induced End MT through TGF-β1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases.
基金the following agencies for financially supporting this work:the National Key Research and Development Program of China(grant no.2024YFA1211000)the National Natural Science Foundation of China(grant nos.22321004 and 22273111).
文摘Photocatalysis opens unique pathways for reductive hydrogenation under mild conditions.Typically,photocatalytic hydrogenation proceeds via single electron transfer(SET),followed by hydrogen atom transfer.Herein,we elucidate that the deliberate arrangement of an electron reservoir and Ni catalysts enables a transition from photoinduced one-to twoelectron transfer,yielding desired products via proton acquisition.Specifically,arranging carbon nitride(CN)that stores multiple photogenerated electrons in proximity to a chemically bonded Ni site accomplishes competitive two-electron/proton hydrogenation of halogenated substrates using water as the hydrogen source,outperforming the SETmediated process.In contrast,the nonchemically bonded Ni and CN system exhibits poor activity for 2e−/H+hydrogenation.Mechanistic studies further reveal that the low-valent Ni+and CN(e−)cooperate to transfer two electrons to the substrate.The catalytic utility of this two-electron mechanism is further underscored by the deuterium labeling of diverse(hetero)arenes and bioactive molecules in D_(2)O,achieving deuterium incorporation of up to 99%.Our work highlights the value of light-driven multipleelectron catalysis that reaches otherwise challenging transformations.
