LAMA2-related congenital muscular dystrophy(LAMA2-CMD),characterized by laminin-α2 deficiency,is debilitating and ultimately fatal.To date,no effective therapy has been clinically available.Laminin-a1,which shares si...LAMA2-related congenital muscular dystrophy(LAMA2-CMD),characterized by laminin-α2 deficiency,is debilitating and ultimately fatal.To date,no effective therapy has been clinically available.Laminin-a1,which shares significant similarities with laminin-a2,has been proven as a viable compensatory modifier.To evaluate its clinical applicability,we establish a Lama2 exon-3-deletion mouse model(dy^(H)/dy^(H)).The dy^(H)/dy^(H)mice exhibit early lethality and typical LAMA2-CMD phenotypes,allowing the evaluation of various endpoints.In dy^(H)/dy^(H)mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation,a nearly doubled median survival is observed,as well as improvements in weight and grip.Significant therapeutical effects are revealed by MRl,serum biochemical indices,and muscle pathology studies.Treating LAMA2-CMD with LAMA1 upregulation is feasible,and early intervention can alleviate symptoms and extend lifespan.Additionally,we reveal the limitations of LAMA1 upregulation,including high-dose mortality and non-sustained expression,which require further optimization in future studies.展开更多
Intelligent electronic devices(IEDs)are interconnected via communication networks and play pivotal roles in transmitting grid-related operational data and executing control instructions.In the context of the heightene...Intelligent electronic devices(IEDs)are interconnected via communication networks and play pivotal roles in transmitting grid-related operational data and executing control instructions.In the context of the heightened security challenges within smart grids,IEDs pose significant risks due to inherent hardware and software vulner-abilities,as well as the openness and vulnerability of communication protocols.Smart grid security,distinct from traditional internet security,mainly relies on monitoring network security events at the platform layer,lacking an effective assessment mechanism for IEDs.Hence,we incorporate considerations for both cyber-attacks and physical faults,presenting security assessment indicators and methods specifically tailored for IEDs.Initially,we outline the security monitoring technology for IEDs,considering the necessary data sources for their security assessment.Subsequently,we classify IEDs and establish a comprehensive security monitoring index system,incorporating factors such as running states,network traffic,and abnormal behaviors.This index system contains 18 indicators in 3 categories.Additionally,we elucidate quantitative methods for various indicators and propose a hybrid security assessment method known as GRCW-hybrid,combining grey relational analysis(GRA),analytic hierarchy process(AHP),and entropy weight method(EWM).According to the proposed assessment method,the security risk level of IEDs can be graded into 6 levels,namely 0,1,2,3,4,and 5.The higher the level,the greater the security risk.Finally,we assess and simulate 15 scenarios in 3 categories,which are based on monitoring indicators and real-world situations encountered by IEDs.The results show that calculated security risk level based on the proposed assessment method are consistent with actual simulation.Thus,the reasonableness and effectiveness of the proposed index system and assessment method are validated.展开更多
Recent findings show that Toll-like receptors(TLRs) expressed in immune cells play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection on ...Recent findings show that Toll-like receptors(TLRs) expressed in immune cells play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection on tissue injury.Furthermore,expression of TLRs in cancer cells is associated with tumor proliferation and invasion.To explore the role of TLRs expression in cervical carcinogenesis in Uighur women,we detected the expressions of TLR3,TLR4,TLR7,and TLR9 in 25 normal cervical tissues,64 cervical intraepithelial neoplasia(CIN) tissues,and 63 cervical squamous cell carcinoma(CSCC) tissues using immunohistochemical staining,as well as human papillomavirus type 16(HPV16) infection using PCR.All samples used in this study were from Xinjiang Uighur women.We found the expression levels of TLR4,TLR7,and TLR9 were significantly higher in CIN and CSCC than in normal controls(P < 0.05).Up-regulation of TLR4 and TLR7 were correlated with tumor differentiation but not FIGO stage or lymph node metastasis(P > 0.05).Up-regulation of TLR9 was correlated with lymph node metastasis(P < 0.05) but not tumor differentiation or FIGO stage(P > 0.05).We also analyzed the correlation between the expressions of TLRs and HPV16 infection and found that the expressions of TLR4 and TLR9 significantly correlated with HPV16 infection in CIN(r = 7.434,P = 0.006;r = 7.123,P = 0.008) and CSCC(r = 6.423,P = 0.001;r = 8.478,P = 0.004),whereas the expression of TLR3 was not significantly different in any of the three groups and had no significant correlation with HPV16 infection.Our results suggest that high expression of TLR4,TLR7,and TLR9 may play important roles in the development and progression of CIN and CSCC in Uighur women,and the expressions of TLR4 and TLR9 can be up-regulated by HPV16 infection.展开更多
3D visualization is one of major problems in “Digital Mine” theory and its technological research field. Through the observation of 3D geological models, spatial structural information, connected with the informatio...3D visualization is one of major problems in “Digital Mine” theory and its technological research field. Through the observation of 3D geological models, spatial structural information, connected with the information of production management hidden in geological data, could be detected. In order to meet the requirement of more efficient coal exploration, a case study of geological characters of the Daliuta Coal Mine is presented in which 3D visual models of the ground surface and geologic bodies are established on the basis of data models and data structures of 3D geology modeling. The main conclusions of this study are as follows: (1) Through analysis and organization of spatial discrete data, the drillhole database is designed with the data of the Daliuta mine; the connections amomg drillhole data are real- ized and displayed in a 3D environment. (2) Combining real data of the Daliuta mine, drillhole visualization is realized in a 3D environment by using the CoalMiner system. (3) The ground surface modeling of the Daliuta coal mine adopted a surface-data model and a TIN data structure. (4) 3D models of coal seams and rock formations of the Daliuta mine are established, which provide a method for the simulation of complex surfaces of geologic bodies. In the end, the models are applied to the Daliuta coal mine and the result shows that better geological effects are obtained.展开更多
The Xiangshan deposit in Jiangxi province is one of the most important uranium deposits in China. The aim of this study is to achieve a better understanding of mineralization in the Xiangshan deposit through numerical...The Xiangshan deposit in Jiangxi province is one of the most important uranium deposits in China. The aim of this study is to achieve a better understanding of mineralization in the Xiangshan deposit through numerical simulation. In order to find the most favorable locations of mineralization and to help further mineral exploration, a coupling deforma- tion and fluid flow model has been established to describe the mineralization process. In this model, the simulation re- constructs the strata deformations under fields of compressive stress and thrust structure on the hanging wall of the Zou-Shi fault. Compared with practical information, the simulation results are consistent with the No. 51 exploration section of the western Xiangshan. In addition, on the basis of geological information provided by previous investigators, the model simulates the flow process of fluids under compressive stress fields. The result suggests that many tensional areas are formed, which can help the fluid flowing upward from deeper parts. The fluid is easy to concentrate on the breccia fractured zone between two volcanic layers, especially on the intersection parts with faults, resulting in the for- mation of favourable locations of mineralization. In addition, the model is significant in guiding the exploration of ura- nium deposits in the western Xiangshan and provides clues for further exploration of deposits.展开更多
The Xiangshan uranium deposit in Jiangxi province is one of the most important uranium deposits in China. The aim of our study is to obtain a better understanding of rock deformation and dilation associated with miner...The Xiangshan uranium deposit in Jiangxi province is one of the most important uranium deposits in China. The aim of our study is to obtain a better understanding of rock deformation and dilation associated with mineralization, to predict the most favorable locations of mineralization, and to assist with future mineral exploration in this deposit. On the basis of geological and structural data from previous studies, we have constructed a coupled deformation and fluid flow numerical model and simulated the faulting deformation and major mechanical factors controlling mineralization in the deposit. Particular attention has been paid to variations in regional stress, distributions of shear strain, volumetric strain and pore pressure. The relationship between the struc-tural/faulting movement and mineralization is obtained through analyzing the deformation state of fault zones. The results suggest that the mineralization is related to volumetric strain, shear strain and pore pressures. The locations displaying all these factors rep-resent the most favorable sites for mineralization. These model results are important for guiding the exploration of new uranium deposits in Xiangshan.展开更多
基金This study received support from the following grants:National Natural Science Foundation of China(82171393 to H.X.)National High Level Hospital Clinical Research Funding(High Quality Clinical Research Project of Peking University First Hospital)(2022CR69 to H.X.)+4 种基金Natural Science Foundation of Beijing Municipality(7212116 to H.X.)National Key Research and Development Program of China(2016YFC0901505 to H.X.)Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases(BZ0317 to H.X.)Research Foundation for Youth Talents of the First Affiliated Hospital of Nanchang University(YFYPY202223 to D.T.)Natural Science Foundation of Beijing Municipality(7242149 to H.L.).
文摘LAMA2-related congenital muscular dystrophy(LAMA2-CMD),characterized by laminin-α2 deficiency,is debilitating and ultimately fatal.To date,no effective therapy has been clinically available.Laminin-a1,which shares significant similarities with laminin-a2,has been proven as a viable compensatory modifier.To evaluate its clinical applicability,we establish a Lama2 exon-3-deletion mouse model(dy^(H)/dy^(H)).The dy^(H)/dy^(H)mice exhibit early lethality and typical LAMA2-CMD phenotypes,allowing the evaluation of various endpoints.In dy^(H)/dy^(H)mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation,a nearly doubled median survival is observed,as well as improvements in weight and grip.Significant therapeutical effects are revealed by MRl,serum biochemical indices,and muscle pathology studies.Treating LAMA2-CMD with LAMA1 upregulation is feasible,and early intervention can alleviate symptoms and extend lifespan.Additionally,we reveal the limitations of LAMA1 upregulation,including high-dose mortality and non-sustained expression,which require further optimization in future studies.
基金The financial support from the Program for Science and Technology of Henan Province of China(Grant No.242102210148)Henan Center for Outstanding Overseas Scientists(Grant No.GZS2022011)Songshan Laboratory Pre-Research Project(Grant No.YYJC032022022).
文摘Intelligent electronic devices(IEDs)are interconnected via communication networks and play pivotal roles in transmitting grid-related operational data and executing control instructions.In the context of the heightened security challenges within smart grids,IEDs pose significant risks due to inherent hardware and software vulner-abilities,as well as the openness and vulnerability of communication protocols.Smart grid security,distinct from traditional internet security,mainly relies on monitoring network security events at the platform layer,lacking an effective assessment mechanism for IEDs.Hence,we incorporate considerations for both cyber-attacks and physical faults,presenting security assessment indicators and methods specifically tailored for IEDs.Initially,we outline the security monitoring technology for IEDs,considering the necessary data sources for their security assessment.Subsequently,we classify IEDs and establish a comprehensive security monitoring index system,incorporating factors such as running states,network traffic,and abnormal behaviors.This index system contains 18 indicators in 3 categories.Additionally,we elucidate quantitative methods for various indicators and propose a hybrid security assessment method known as GRCW-hybrid,combining grey relational analysis(GRA),analytic hierarchy process(AHP),and entropy weight method(EWM).According to the proposed assessment method,the security risk level of IEDs can be graded into 6 levels,namely 0,1,2,3,4,and 5.The higher the level,the greater the security risk.Finally,we assess and simulate 15 scenarios in 3 categories,which are based on monitoring indicators and real-world situations encountered by IEDs.The results show that calculated security risk level based on the proposed assessment method are consistent with actual simulation.Thus,the reasonableness and effectiveness of the proposed index system and assessment method are validated.
基金supported by a grant from NationalNatural Science Foundation of China (No.81060164)
文摘Recent findings show that Toll-like receptors(TLRs) expressed in immune cells play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection on tissue injury.Furthermore,expression of TLRs in cancer cells is associated with tumor proliferation and invasion.To explore the role of TLRs expression in cervical carcinogenesis in Uighur women,we detected the expressions of TLR3,TLR4,TLR7,and TLR9 in 25 normal cervical tissues,64 cervical intraepithelial neoplasia(CIN) tissues,and 63 cervical squamous cell carcinoma(CSCC) tissues using immunohistochemical staining,as well as human papillomavirus type 16(HPV16) infection using PCR.All samples used in this study were from Xinjiang Uighur women.We found the expression levels of TLR4,TLR7,and TLR9 were significantly higher in CIN and CSCC than in normal controls(P < 0.05).Up-regulation of TLR4 and TLR7 were correlated with tumor differentiation but not FIGO stage or lymph node metastasis(P > 0.05).Up-regulation of TLR9 was correlated with lymph node metastasis(P < 0.05) but not tumor differentiation or FIGO stage(P > 0.05).We also analyzed the correlation between the expressions of TLRs and HPV16 infection and found that the expressions of TLR4 and TLR9 significantly correlated with HPV16 infection in CIN(r = 7.434,P = 0.006;r = 7.123,P = 0.008) and CSCC(r = 6.423,P = 0.001;r = 8.478,P = 0.004),whereas the expression of TLR3 was not significantly different in any of the three groups and had no significant correlation with HPV16 infection.Our results suggest that high expression of TLR4,TLR7,and TLR9 may play important roles in the development and progression of CIN and CSCC in Uighur women,and the expressions of TLR4 and TLR9 can be up-regulated by HPV16 infection.
基金Project 2002CB412601 supported by Chinese Ministry of Science and Technology
文摘3D visualization is one of major problems in “Digital Mine” theory and its technological research field. Through the observation of 3D geological models, spatial structural information, connected with the information of production management hidden in geological data, could be detected. In order to meet the requirement of more efficient coal exploration, a case study of geological characters of the Daliuta Coal Mine is presented in which 3D visual models of the ground surface and geologic bodies are established on the basis of data models and data structures of 3D geology modeling. The main conclusions of this study are as follows: (1) Through analysis and organization of spatial discrete data, the drillhole database is designed with the data of the Daliuta mine; the connections amomg drillhole data are real- ized and displayed in a 3D environment. (2) Combining real data of the Daliuta mine, drillhole visualization is realized in a 3D environment by using the CoalMiner system. (3) The ground surface modeling of the Daliuta coal mine adopted a surface-data model and a TIN data structure. (4) 3D models of coal seams and rock formations of the Daliuta mine are established, which provide a method for the simulation of complex surfaces of geologic bodies. In the end, the models are applied to the Daliuta coal mine and the result shows that better geological effects are obtained.
基金Projects GPMR0547 supported by the State Key Laboratory of Geological Processes and Mineral Resources, China University of Geosciences, and 2002 CB 412601 by the Chinese Ministry of Science and Technology
文摘The Xiangshan deposit in Jiangxi province is one of the most important uranium deposits in China. The aim of this study is to achieve a better understanding of mineralization in the Xiangshan deposit through numerical simulation. In order to find the most favorable locations of mineralization and to help further mineral exploration, a coupling deforma- tion and fluid flow model has been established to describe the mineralization process. In this model, the simulation re- constructs the strata deformations under fields of compressive stress and thrust structure on the hanging wall of the Zou-Shi fault. Compared with practical information, the simulation results are consistent with the No. 51 exploration section of the western Xiangshan. In addition, on the basis of geological information provided by previous investigators, the model simulates the flow process of fluids under compressive stress fields. The result suggests that many tensional areas are formed, which can help the fluid flowing upward from deeper parts. The fluid is easy to concentrate on the breccia fractured zone between two volcanic layers, especially on the intersection parts with faults, resulting in the for- mation of favourable locations of mineralization. In addition, the model is significant in guiding the exploration of ura- nium deposits in the western Xiangshan and provides clues for further exploration of deposits.
基金Project GPMR0547 supported by the State Key Laboratory of Geological Process and Mineral Resources, China University of Geosciences
文摘The Xiangshan uranium deposit in Jiangxi province is one of the most important uranium deposits in China. The aim of our study is to obtain a better understanding of rock deformation and dilation associated with mineralization, to predict the most favorable locations of mineralization, and to assist with future mineral exploration in this deposit. On the basis of geological and structural data from previous studies, we have constructed a coupled deformation and fluid flow numerical model and simulated the faulting deformation and major mechanical factors controlling mineralization in the deposit. Particular attention has been paid to variations in regional stress, distributions of shear strain, volumetric strain and pore pressure. The relationship between the struc-tural/faulting movement and mineralization is obtained through analyzing the deformation state of fault zones. The results suggest that the mineralization is related to volumetric strain, shear strain and pore pressures. The locations displaying all these factors rep-resent the most favorable sites for mineralization. These model results are important for guiding the exploration of new uranium deposits in Xiangshan.
