Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl gro...In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.展开更多
Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy.Mutations in the TUFM gene are known ...Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy.Mutations in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)complexes.The development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical management.In this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid cycle.Leveraging this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing COXPD4.Our data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.展开更多
In recent years, West Africa has been confronted with hydro-climatic disasters causing crises in both urban and rural areas. The tragedy in the occurrence of such events lies in the recurrent aspect of high water and ...In recent years, West Africa has been confronted with hydro-climatic disasters causing crises in both urban and rural areas. The tragedy in the occurrence of such events lies in the recurrent aspect of high water and associated floods. The devastating floods observed in Africa’s major rivers have revealed the need to understand the causes of these phenomena and to predict their behavior in order to improve the safety of exposed people and property. The aim of this study is to reproduce flood flows using the GR4J (Rural Engineering Four Daily Parameters) model to analyze flood risk in the Oti watershed in Togo. Daily data on flows (m3/s), potential evapotranspiration (mm/day) and average precipitation (mm) over the basin from 1961-2022 collected at the National Meteorological Agency of Togo (ANAMET) and the Department of Water Resources in Lome, were used with the R software package airGR. The Data from the West African Cordex program from 1961-2100 were used to analyze projected flows. The results obtained show the GR4J model’s effectiveness in reproducing flood flows, indicating that observed flows are well simulated during the calibration and validation periods, with KGE values ranging from 0.73 to 0.85 at calibration and 0.62 to 0.81 at validation. These KGE values reflect the good performance of the GR4J model in simulating flood flows in the watershed. However, a deterioration in the KGE value was observed over the second validation period. Under these conditions, there may be false or missed alerts for flood prediction, and the use of this model should be treated with the utmost caution for decision-support purposes.展开更多
The longitude tensile properties of 3-Dimension-4-directional（3D-4d） braided C/Si C composites（CMCs） were investigated with the help of a double scale model. This model involves micro-scale and unit-cell scale. In...The longitude tensile properties of 3-Dimension-4-directional（3D-4d） braided C/Si C composites（CMCs） were investigated with the help of a double scale model. This model involves micro-scale and unit-cell scale. In micro-scale, the tensile properties of fiber tows which involves matrix cracking, interfacial debonding, and fiber failure are studied. The unit-cell scale model can reflect the braided structure and simulate the tensile properties of 3D-4d CMCs by introducing the tensile properties of fiber tows into it. Quasi-static tensile tests of 3D-4d braided CMCs were performed on a PWS-100 test system. The predicted tensile stressstrain curve by the double scale model is in good agreement with that of the experimental results.展开更多
This paper describes an extension and a new foundation of the Standard Model of particle physics based on a SU(4)-force called hyper-color, and on preon subparticles. The hyper-color force is a generalization of the S...This paper describes an extension and a new foundation of the Standard Model of particle physics based on a SU(4)-force called hyper-color, and on preon subparticles. The hyper-color force is a generalization of the SU(2)-based weak interaction and the SU(1)-based right-chiral self-interaction, in which the W-and the Z-bosons are Yukawa residual-field-carriers of the hyper-color force, in the same sense as the pions are the residual-field-carriers of the color SU(3) interaction. Using the method of numerical minimization of the SU(4)-action based on this model, the masses and the inner structure of leptons, quarks and weak bosons are calculated: the mass results are very close to the experimental values. We calculate also precisely the value of the Cabibbo angle, so the mixing matrices of the Standard model, CKM matrix for quarks and PMNS matrix for neutrinos can also be calculated. In total, we reduce the 29 parameters of the Standard Model to a total of 7 parameters.展开更多
As an important part of railway lines, the healthy service status of track fasteners was very important to ensure the safety of trains. The application of deep learning algorithms was becoming an important method to r...As an important part of railway lines, the healthy service status of track fasteners was very important to ensure the safety of trains. The application of deep learning algorithms was becoming an important method to realize its state detection. However, there was often a deficiency that the detection accuracy and calculation speed of model were difficult to balance, when the traditional deep learning model is used to detect the service state of track fasteners. Targeting this issue, an improved Yolov4 model for detecting the service status of track fasteners was proposed. Firstly, the Mixup data augmentation technology was introduced into Yolov4 model to enhance the generalization ability of model. Secondly, the MobileNet-V2 lightweight network was employed in lieu of the CSPDarknet53 network as the backbone, thereby reducing the number of algorithm parameters and improving the model’s computational efficiency. Finally, the SE attention mechanism was incorporated to boost the importance of rail fastener identification by emphasizing relevant image features, ensuring that the network’s focus was primarily on the fasteners being inspected. The algorithm achieved both high precision and high speed operation of the rail fastener service state detection, while realizing the lightweight of model. The experimental results revealed that, the MAP value of the rail fastener service state detection algorithm based on the improved Yolov4 model reaches 83.2%, which is 2.83% higher than that of the traditional Yolov4 model, and the calculation speed was improved by 67.39%. Compared with the traditional Yolov4 model, the proposed method achieved the collaborative optimization of detection accuracy and calculation speed.展开更多
Gas separation is a critical application of gas hydrates,and accurately predicting separation performance is crucial.In this study,we used thermodynamic calculations to predict the equilibrium phase of gas hydrates fo...Gas separation is a critical application of gas hydrates,and accurately predicting separation performance is crucial.In this study,we used thermodynamic calculations to predict the equilibrium phase of gas hydrates for various mole fractions of CO_(2)+CH_(4)gas mixtures.We also determined the mole fraction of each gas component trapped within the hydrate clathrate.To predict the equilibrium points,we used the SoaveeRedlicheKwong(SRK)equation of state for the gas phase,the nonrandom two-liquid(NRTL)model for the liquid phase,and the CheneGuo model for the hydrate phase.We modified the hydrate fugacity formula and introduced a new function to improve the accuracy of the CheneGuo model.By incorporating experimental equilibrium results from our study and another study,we developed a correlation based on gas mixture composition and temperature,resulting in highly accurate predictions.The use of this new correlation for hydrate fugacity calculation significantly improved precision,as evidenced by an average absolute deviation percent of calculated pressures(AADP)of 1.34%for pure CO_(2)and 1.25%for CH_(4).When considering the 27 data points of different CO_(2)+CH_(4)mixtures,the AADP%was 1.98%.To implement the model to predict equilibrium phases,we used the CheneGuo framework to determine the mole fraction of each gas component in the hydrate mixture.Interestingly,we discovered a linear correlation between the CO_(2)mole fraction in the hydrate and equilibrium pressure,with a slope of approximately 0.001 and a y-intercept of less than one,for all gas compositions.Therefore,we can conclude that low thermodynamic conditions(temperature and pressure)result in a high CO_(2)mole fraction in the hydrate phase and great separation efficiency.展开更多
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金The authors gratefully acknowledge the financial support of the Natural Science Foundation of China,China(Grant No.21975082 and 21736003)the Guangdong Basic and Applied Basic Research Foundation(Grant Number:2019A1515011472 and 2022A1515011341)the Science and Technology Program of Guangzhou(Grant Number:202102080479).
文摘In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.
基金supported by the National Natural Science Foundation of China(#92254302 and#32293202 to S.J.)National Key Research and Development(#2019YFA0801403 to S.J.).
文摘Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy.Mutations in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)complexes.The development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical management.In this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid cycle.Leveraging this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing COXPD4.Our data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.
文摘In recent years, West Africa has been confronted with hydro-climatic disasters causing crises in both urban and rural areas. The tragedy in the occurrence of such events lies in the recurrent aspect of high water and associated floods. The devastating floods observed in Africa’s major rivers have revealed the need to understand the causes of these phenomena and to predict their behavior in order to improve the safety of exposed people and property. The aim of this study is to reproduce flood flows using the GR4J (Rural Engineering Four Daily Parameters) model to analyze flood risk in the Oti watershed in Togo. Daily data on flows (m3/s), potential evapotranspiration (mm/day) and average precipitation (mm) over the basin from 1961-2022 collected at the National Meteorological Agency of Togo (ANAMET) and the Department of Water Resources in Lome, were used with the R software package airGR. The Data from the West African Cordex program from 1961-2100 were used to analyze projected flows. The results obtained show the GR4J model’s effectiveness in reproducing flood flows, indicating that observed flows are well simulated during the calibration and validation periods, with KGE values ranging from 0.73 to 0.85 at calibration and 0.62 to 0.81 at validation. These KGE values reflect the good performance of the GR4J model in simulating flood flows in the watershed. However, a deterioration in the KGE value was observed over the second validation period. Under these conditions, there may be false or missed alerts for flood prediction, and the use of this model should be treated with the utmost caution for decision-support purposes.
基金Funded by the National Basic Research Program of Chinathe National Natural Science Foundation of China(51675266)+3 种基金the Aeronautical Science Foundation of China(2014ZB52024)the Fundamental Research Funds for the Central Universities(NJ20160038)the Jiangsu Innovation Program for Graduate Education(CXLX13_165)the Fundamental Research Funds for the Central Universities
文摘The longitude tensile properties of 3-Dimension-4-directional（3D-4d） braided C/Si C composites（CMCs） were investigated with the help of a double scale model. This model involves micro-scale and unit-cell scale. In micro-scale, the tensile properties of fiber tows which involves matrix cracking, interfacial debonding, and fiber failure are studied. The unit-cell scale model can reflect the braided structure and simulate the tensile properties of 3D-4d CMCs by introducing the tensile properties of fiber tows into it. Quasi-static tensile tests of 3D-4d braided CMCs were performed on a PWS-100 test system. The predicted tensile stressstrain curve by the double scale model is in good agreement with that of the experimental results.
文摘This paper describes an extension and a new foundation of the Standard Model of particle physics based on a SU(4)-force called hyper-color, and on preon subparticles. The hyper-color force is a generalization of the SU(2)-based weak interaction and the SU(1)-based right-chiral self-interaction, in which the W-and the Z-bosons are Yukawa residual-field-carriers of the hyper-color force, in the same sense as the pions are the residual-field-carriers of the color SU(3) interaction. Using the method of numerical minimization of the SU(4)-action based on this model, the masses and the inner structure of leptons, quarks and weak bosons are calculated: the mass results are very close to the experimental values. We calculate also precisely the value of the Cabibbo angle, so the mixing matrices of the Standard model, CKM matrix for quarks and PMNS matrix for neutrinos can also be calculated. In total, we reduce the 29 parameters of the Standard Model to a total of 7 parameters.
文摘As an important part of railway lines, the healthy service status of track fasteners was very important to ensure the safety of trains. The application of deep learning algorithms was becoming an important method to realize its state detection. However, there was often a deficiency that the detection accuracy and calculation speed of model were difficult to balance, when the traditional deep learning model is used to detect the service state of track fasteners. Targeting this issue, an improved Yolov4 model for detecting the service status of track fasteners was proposed. Firstly, the Mixup data augmentation technology was introduced into Yolov4 model to enhance the generalization ability of model. Secondly, the MobileNet-V2 lightweight network was employed in lieu of the CSPDarknet53 network as the backbone, thereby reducing the number of algorithm parameters and improving the model’s computational efficiency. Finally, the SE attention mechanism was incorporated to boost the importance of rail fastener identification by emphasizing relevant image features, ensuring that the network’s focus was primarily on the fasteners being inspected. The algorithm achieved both high precision and high speed operation of the rail fastener service state detection, while realizing the lightweight of model. The experimental results revealed that, the MAP value of the rail fastener service state detection algorithm based on the improved Yolov4 model reaches 83.2%, which is 2.83% higher than that of the traditional Yolov4 model, and the calculation speed was improved by 67.39%. Compared with the traditional Yolov4 model, the proposed method achieved the collaborative optimization of detection accuracy and calculation speed.
文摘Gas separation is a critical application of gas hydrates,and accurately predicting separation performance is crucial.In this study,we used thermodynamic calculations to predict the equilibrium phase of gas hydrates for various mole fractions of CO_(2)+CH_(4)gas mixtures.We also determined the mole fraction of each gas component trapped within the hydrate clathrate.To predict the equilibrium points,we used the SoaveeRedlicheKwong(SRK)equation of state for the gas phase,the nonrandom two-liquid(NRTL)model for the liquid phase,and the CheneGuo model for the hydrate phase.We modified the hydrate fugacity formula and introduced a new function to improve the accuracy of the CheneGuo model.By incorporating experimental equilibrium results from our study and another study,we developed a correlation based on gas mixture composition and temperature,resulting in highly accurate predictions.The use of this new correlation for hydrate fugacity calculation significantly improved precision,as evidenced by an average absolute deviation percent of calculated pressures(AADP)of 1.34%for pure CO_(2)and 1.25%for CH_(4).When considering the 27 data points of different CO_(2)+CH_(4)mixtures,the AADP%was 1.98%.To implement the model to predict equilibrium phases,we used the CheneGuo framework to determine the mole fraction of each gas component in the hydrate mixture.Interestingly,we discovered a linear correlation between the CO_(2)mole fraction in the hydrate and equilibrium pressure,with a slope of approximately 0.001 and a y-intercept of less than one,for all gas compositions.Therefore,we can conclude that low thermodynamic conditions(temperature and pressure)result in a high CO_(2)mole fraction in the hydrate phase and great separation efficiency.
