Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physi...Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.展开更多
A mathematical hydraulic support self-tracking model for three-machine cooperative mining is proposed to address low efficiency and difficulties in strategy evaluation of a fully mechanized coal face.The proposed mode...A mathematical hydraulic support self-tracking model for three-machine cooperative mining is proposed to address low efficiency and difficulties in strategy evaluation of a fully mechanized coal face.The proposed model uses the coordinates and traction speed of the shearer to calculate the frequency of the circular hydraulic support and realize the coordinated operation of the three-machine mining technology.A unity3d hardware-in-the-loop simulation experimental hearer and hydraulic support platform was used to validate the model of autonomous follow-up.The results indicate that collaborative control of coal mining allowed for an efficiency 3.76%higher than under automatic operation mode and 46.03%higher than under manual control;thus,The mathematical model provided an improved production efficiency of the fully mechanized mining face.The mathematical model also provides a more intelligent and reliable security support,and improves the intelligent level of hydraulic support follow-up control.展开更多
For a study of the movement and deformation of coal-rock mass and low protected seams below a stope,as well as for fracture developments and rules of evolution of permeability,we designed a plane strain model test sta...For a study of the movement and deformation of coal-rock mass and low protected seams below a stope,as well as for fracture developments and rules of evolution of permeability,we designed a plane strain model test stand to carry out model tests of similar materials in order to improve the effect of gas drainage from low protected seams and to measure the movement and deformation of coal-rock mass using a method of non-contact close-range photogrammetry.Our results show that 1) using paraffin melting to take the place of coal seam mining can satisfy the mining conditions of a protective seam;2) coal-rock mass under goafs has an upward movement after the protective seam has been mined,causing floor heaving;3) low protected seams become swollen and deformed,providing a good pressure-relief effect and causing the coal-rock mass under both sides of coal pillars to become deformed by compression and 4) the evolution of permeability of low protected seams follows the way of initial values→a slight decrease→a great increase→stability→final decrease.Simultaneously,the coefficient of air permeability increased at a decreasing rate with an increase in interlayer spacing.展开更多
Attacking time-sensitive targets has rigid demands for the timeliness and reliability of information transmission, while typical Media Access Control（MAC） designed for this application works well only in very light-...Attacking time-sensitive targets has rigid demands for the timeliness and reliability of information transmission, while typical Media Access Control（MAC） designed for this application works well only in very light-load scenarios; as a consequence, the performances of system throughput and channel utilization are degraded. For this problem, a feedback-retransmission based asynchronous FRequency hopping Media Access（FRMA） control protocol is proposed. Burst communication, asynchronous Frequency Hopping（FH）, channel coding, and feedback retransmission are utilized in FRMA. With the mechanism of asynchronous FH, immediate packet transmission and multi-packet reception can be realized, and thus the timeliness is improved.Furthermore, reliability can be achieved via channel coding and feedback retransmission. With theories of queuing theory, Markov model, packets collision model, and discrete Laplace transformation, the formulas of packet success probability, system throughput, average packet end-to-end delay, and delay distribution are obtained. The approximation accuracy of theoretical derivation is verified by experimental results. Within a light-load network, the proposed FRMA has the ability of millisecond delay and 99% reliability as well as outperforms the non-feedback-retransmission based asynchronous frequency hopping media access control protocol.展开更多
Reverberation is significant in shallow water and produces obvious notches in OBC spec- tra. It also degrades the quality of sections and increases the difficulty of processing and interpretation. This article present...Reverberation is significant in shallow water and produces obvious notches in OBC spec- tra. It also degrades the quality of sections and increases the difficulty of processing and interpretation. This article presents the relationship between notch, shooting depth, and seabed depth based on the seismic convolution model. Forward modelling based on wave equation theory is used to verify this relationship. Dual-sensor summation is applied to suppress receiver-side multiples and remove notches according to the opposite response of geophones and hydrophones to down-going wave fields based on a detailed analysis of the OBC technique. The good results obtained in practical applications reveal the effectiveness of this method.展开更多
The application of bio-inspired computational techniques to the field of condition monitoring is addressed. First, the bio-inspired computational techniques are briefly addressed; the advantages and disadvantages of t...The application of bio-inspired computational techniques to the field of condition monitoring is addressed. First, the bio-inspired computational techniques are briefly addressed; the advantages and disadvantages of these computational methods are made clear. Then, the roles of condition monitoring in the predictive maintenance and failures prediction and the development trends of condition monitoring are discussed. Finally, a case study on the condition monitoring of grinding machine is described, which shows the application of bio-inspired computational technique to a practical condition monitoring system.展开更多
Aiming at the detection failure of strong noise interference in the dual channel of the dual-sequence frequency hopping(DSFH),the scale transformation stochastic resonance(STSR)is applied for the first time,and the ou...Aiming at the detection failure of strong noise interference in the dual channel of the dual-sequence frequency hopping(DSFH),the scale transformation stochastic resonance(STSR)is applied for the first time,and the output signal to noise ratio(SNR)is raised effectively,at the same time,the symbol reception is completed for DSFH at low input SNR.Firstly,the radio frequency(RF)and intermediate frequency(IF)signals are analyzed based on the super-heterodyne reception of DSFH;secondly,the equations of probability density function(PDF),output power spectrum and SNR of the STSR output are derived for the IF signal;finally,the algorithm of the optimal matching STSR is proposed with the optimal matching parameters.The simulation results show that the algorithm can effectively solve the detection failure,as the global output SNR of DSFH is strongly improved that the output SNR can reach-17.72 d B when the input SNR is-20 d B after the processing of the optimal matching STSR.展开更多
As one of the divisions in China Southern Power Grid, Yunnan Power Grid Corporation has conducted research and demonstration projects on multiple smart grid technologies to improve the power system reliability, save o...As one of the divisions in China Southern Power Grid, Yunnan Power Grid Corporation has conducted research and demonstration projects on multiple smart grid technologies to improve the power system reliability, save operation cost and enhance measurement accuracy. In this paper, we will introduce The Study of Yunnan Mountain Substation Data Aggregation Technology based on Sparse Methods. Most substations are built in the mountain, the complex geological conditions and poor natural conditions put forward higher requirements on the substation running and real-time comprehensive monitoring of substation system. Processing and polymerization research of large amounts of the monitoring data and information is studied in this article. This paper introduces the sparse methods and then explains the thinning algorithm, especially new algorithm is proposed. Finally, the substation sparse method architecture is put forward and the simulation experiment was carried out to prove the feasibility and effectiveness of the proposed method.展开更多
The visualization of drugs in living systems has become key techniques in modern therapeutics.Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization....The visualization of drugs in living systems has become key techniques in modern therapeutics.Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization.At the subcellular level,super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs.Moving beyond subcellular imaging,researchers have integrated multiple modes,like optical near-infrared II imaging,to study the complex spatiotemporal interactions between drugs and their surroundings.By combining these visualization approaches,researchers gain supplementary information on physiological parameters,metabolic activity,and tissue composition,leading to a comprehensive understanding of drug behavior.This review focuses on cutting-edge technologies in drug visualization,particularly fluorescence imaging,and the main types of fluorescent molecules used.Additionally,we discuss current challenges and prospects in targeted drug research,emphasizing the importance of multidisciplinary cooperation in advancing drug visualization.With the integration of advanced imaging technology and molecular design,drug visualization has the potential to redefine our understanding of pharmacology,enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.展开更多
Rural tourism is an important means of comprehensively promoting the rural revitalisation of industry andpractising the concept of“two mountains theory”.Rural tourism transforms the resource advantages of rural area...Rural tourism is an important means of comprehensively promoting the rural revitalisation of industry andpractising the concept of“two mountains theory”.Rural tourism transforms the resource advantages of rural areasinto economic advantages,but its development entails problems such as the unfair distribution of benefits,uncleardistribution mechanisms,and the non-standardised compensation of benefits.Therefore,finding a mode of governance of rural tourism that can effectively achieve sustainable development is an urgent issue that warrants attention.Taking Jukou Township in Fujian Province as a case,this study constructs a logical framework linking theEco-bank model and rural tourism governance and reveals the practicality and sustainability of rural tourism governance under the Eco-bank model.The study shows the following.(1)As a kind of innovative mechanism forachieving the transformation of resource value through the participation of multiple subjects,the Eco-bank modelsolves the development dilemma of rural tourism through the integration of decentralised resource managementrights,the establishment of property rights constraints and supervision mechanisms for the coordination of stakeholder interests,and the linkage and development of internal and external resources of the countryside.(2)JukouTownship has built a resource operation platform for“ancient house Eco-bank”based on ancient house resourcesand ecological tourism resources.The construction of a rural governance mechanism that combines village collectives,new township elites,villagers,high-end art operation units,and multiple institutional governance entities effectively converts idle ancient houses and high-quality ecological tourism resources into assets and funds to promote the development and growth of the rural collective economy while effectively promoting the stable and sustainable development of the cultural tourism industry in Jukou Township.展开更多
The governance effects of directors’and officers’liability insurance(D&O insurance),an important tool for risk diversification,are of strong concern in the capital market.Using a sample of Chinese A-share listed...The governance effects of directors’and officers’liability insurance(D&O insurance),an important tool for risk diversification,are of strong concern in the capital market.Using a sample of Chinese A-share listed firms from2009 to 2018,we examine the impact of D&O insurance on excess corporate leverage.We find that D&O insurance is negatively associated with excess corporate leverage and that this result is consistent with a series of robustness tests.Further analyses show that D&O insurance impedes excess corporate leverage mainly because of its effect on external monitoring.The effect is more pronounced for firms that are state-owned,have political connections and are located in provinces with low marketization than for other firms.展开更多
Kirsten rat sarcoma(KRAS)mutant non-small cell lung cancer(NSCLC)has distinct co-mutational profiles.Approximately 20%of KRAS mutant NSCLC cases underwent loss-of-function mutation of Kelch-like ECH-associated protein...Kirsten rat sarcoma(KRAS)mutant non-small cell lung cancer(NSCLC)has distinct co-mutational profiles.Approximately 20%of KRAS mutant NSCLC cases underwent loss-of-function mutation of Kelch-like ECH-associated protein 1(KEAP1)gene,namely KRAS-KEAP1 comutation(KK)type,which exhibited a poorer immune checkpoint inhibitor(ICl)response compared with individual KRAS mutation(K)type tumors.i Recent studies suggest that K-type tumors are referred to as"hot tumors"while KK-type tumors are as"cold tumors".Therefore,clarifying the molecular mechanism of the poor IClresponsive phenotype of KK-type tumors is the key to improving the clinical efficacy and breaking through the therapy bottleneck.Co-mutations could regulate the immune contexture to reshape the tumor immune microenvironment(TIME)。展开更多
Posttranslational modifications(PTMs)of proteins,including chromatin modifiers,play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties.However,the roles ...Posttranslational modifications(PTMs)of proteins,including chromatin modifiers,play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties.However,the roles of Lymphoid-specific helicase(LSH),a DNA methylation modifier,in modulating stem-like properties in cancer are still not clearly clarified.Therefore,exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH.Here,we demonstrate that LSH is capable to undergo PTMs,including methylation and phosphorylation.The arginine methyltransferase PRMT5 can methylate LSH at R309 residue,meanwhile,LSH could as well be phosphorylated by MAPK1 kinase at S503 residue.We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue,which eventually promoting stem-like properties in lung cancer.Whereas,phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties,indicating the critical roles of LSH PTMs in modulating stem-like properties.Thus,our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.展开更多
基金National Natural Science Foundation of China(32202800)Natural Science Foundation of Heilongjiang Province(LH2022C104)+1 种基金Heilongjiang Province Education Department Fundamental Scientifc Research Funds(145109516)Qiqihar University Graduate Innovative Research Project(YJSCX2022016).
文摘Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.
基金This work was supported by the Project funded by China Postdoctoral Science Foundation under Grant 2019M651081the Merit Funding for the Returned Overseas Personnel Sci-Tech Activities of Shanxi Province under Grant 2016 and Key Research and Development Program of Shanxi(2019)and Innovation Programs of Higher Education Institutions in Shanxi(2019L0305).
文摘A mathematical hydraulic support self-tracking model for three-machine cooperative mining is proposed to address low efficiency and difficulties in strategy evaluation of a fully mechanized coal face.The proposed model uses the coordinates and traction speed of the shearer to calculate the frequency of the circular hydraulic support and realize the coordinated operation of the three-machine mining technology.A unity3d hardware-in-the-loop simulation experimental hearer and hydraulic support platform was used to validate the model of autonomous follow-up.The results indicate that collaborative control of coal mining allowed for an efficiency 3.76%higher than under automatic operation mode and 46.03%higher than under manual control;thus,The mathematical model provided an improved production efficiency of the fully mechanized mining face.The mathematical model also provides a more intelligent and reliable security support,and improves the intelligent level of hydraulic support follow-up control.
基金the Major Programs of the National Basic Research Program of China (No.2005CB221503)the National Natural Science Foundation of China (Nos. 70533050 and 50674089) for their support of this project
文摘For a study of the movement and deformation of coal-rock mass and low protected seams below a stope,as well as for fracture developments and rules of evolution of permeability,we designed a plane strain model test stand to carry out model tests of similar materials in order to improve the effect of gas drainage from low protected seams and to measure the movement and deformation of coal-rock mass using a method of non-contact close-range photogrammetry.Our results show that 1) using paraffin melting to take the place of coal seam mining can satisfy the mining conditions of a protective seam;2) coal-rock mass under goafs has an upward movement after the protective seam has been mined,causing floor heaving;3) low protected seams become swollen and deformed,providing a good pressure-relief effect and causing the coal-rock mass under both sides of coal pillars to become deformed by compression and 4) the evolution of permeability of low protected seams follows the way of initial values→a slight decrease→a great increase→stability→final decrease.Simultaneously,the coefficient of air permeability increased at a decreasing rate with an increase in interlayer spacing.
基金supported by the National Natural Science Foundation of China(No.61501496)
文摘Attacking time-sensitive targets has rigid demands for the timeliness and reliability of information transmission, while typical Media Access Control（MAC） designed for this application works well only in very light-load scenarios; as a consequence, the performances of system throughput and channel utilization are degraded. For this problem, a feedback-retransmission based asynchronous FRequency hopping Media Access（FRMA） control protocol is proposed. Burst communication, asynchronous Frequency Hopping（FH）, channel coding, and feedback retransmission are utilized in FRMA. With the mechanism of asynchronous FH, immediate packet transmission and multi-packet reception can be realized, and thus the timeliness is improved.Furthermore, reliability can be achieved via channel coding and feedback retransmission. With theories of queuing theory, Markov model, packets collision model, and discrete Laplace transformation, the formulas of packet success probability, system throughput, average packet end-to-end delay, and delay distribution are obtained. The approximation accuracy of theoretical derivation is verified by experimental results. Within a light-load network, the proposed FRMA has the ability of millisecond delay and 99% reliability as well as outperforms the non-feedback-retransmission based asynchronous frequency hopping media access control protocol.
基金supported by the National Natural Science Foundation of China(Nos.41176077 and 41074077)the Key Laboratory of Marine Hydrocarbon Resources and Environmental Geology,Ministry of Land and Resources of China(No.MRE201303)
文摘Reverberation is significant in shallow water and produces obvious notches in OBC spec- tra. It also degrades the quality of sections and increases the difficulty of processing and interpretation. This article presents the relationship between notch, shooting depth, and seabed depth based on the seismic convolution model. Forward modelling based on wave equation theory is used to verify this relationship. Dual-sensor summation is applied to suppress receiver-side multiples and remove notches according to the opposite response of geophones and hydrophones to down-going wave fields based on a detailed analysis of the OBC technique. The good results obtained in practical applications reveal the effectiveness of this method.
基金supported by the National Natural Science Foundation of China ( No. 61025019No. 90820016)+1 种基金Program for New Century Excellent Talents in University ( No. NECT-07-0735)Natural Science Foundation of Hebei ( No. F2009001638)
文摘The application of bio-inspired computational techniques to the field of condition monitoring is addressed. First, the bio-inspired computational techniques are briefly addressed; the advantages and disadvantages of these computational methods are made clear. Then, the roles of condition monitoring in the predictive maintenance and failures prediction and the development trends of condition monitoring are discussed. Finally, a case study on the condition monitoring of grinding machine is described, which shows the application of bio-inspired computational technique to a practical condition monitoring system.
基金the Natural Science of Foundation of Hebei Province(No.F2017506006)
文摘Aiming at the detection failure of strong noise interference in the dual channel of the dual-sequence frequency hopping(DSFH),the scale transformation stochastic resonance(STSR)is applied for the first time,and the output signal to noise ratio(SNR)is raised effectively,at the same time,the symbol reception is completed for DSFH at low input SNR.Firstly,the radio frequency(RF)and intermediate frequency(IF)signals are analyzed based on the super-heterodyne reception of DSFH;secondly,the equations of probability density function(PDF),output power spectrum and SNR of the STSR output are derived for the IF signal;finally,the algorithm of the optimal matching STSR is proposed with the optimal matching parameters.The simulation results show that the algorithm can effectively solve the detection failure,as the global output SNR of DSFH is strongly improved that the output SNR can reach-17.72 d B when the input SNR is-20 d B after the processing of the optimal matching STSR.
文摘As one of the divisions in China Southern Power Grid, Yunnan Power Grid Corporation has conducted research and demonstration projects on multiple smart grid technologies to improve the power system reliability, save operation cost and enhance measurement accuracy. In this paper, we will introduce The Study of Yunnan Mountain Substation Data Aggregation Technology based on Sparse Methods. Most substations are built in the mountain, the complex geological conditions and poor natural conditions put forward higher requirements on the substation running and real-time comprehensive monitoring of substation system. Processing and polymerization research of large amounts of the monitoring data and information is studied in this article. This paper introduces the sparse methods and then explains the thinning algorithm, especially new algorithm is proposed. Finally, the substation sparse method architecture is put forward and the simulation experiment was carried out to prove the feasibility and effectiveness of the proposed method.
基金supported by the Shandong Province Key R&D Program(Major Technological Innovation Project,2021CXGC010501,China)National Natural Science Foundation of China(Nos.22107059,22007060,32300957,82141209)+9 种基金Young Elite Scientists Sponsorship Program by CACM,China(CACM-2023-QNRC1-02)the key Program of Natural Science Foundation of Shandong Province(ZR2023ZD25,China)Natural Science Foundation of Shandong Province(ZR2021QH057,ZR2022QH304,ZR2020QB166,ZR2023QH427,China)Innovation Team of Shandong Higher School Youth Innovation Technology Program(2021KJ035,2022KJ197,China)Taishan Scholars Project in Shandong Province,China(TSPD20181218 TSTP20230633 TSQN202211221)Shandong Science Fund for Excellent Young Scholars(ZR2022YQ66,China)Jinan New 20 Policies for Higher Education Funding(202228048,China)Natural Science Foundation of Shandong Province(Joint Fundation for Innovation and Development,ZR2022LZY021,China)Youth Qihuang Scholars Support Program of the State Administration of Traditional Chinese Medicine,Tianjin Graduate Research Innovation Project(General Project,2022BKY180,China)TUTCM Graduate Research Innovation Project(General Project)and Shandong Province Traditional Chinese Medicine Science and Technology Project(M-2023208,China).
文摘The visualization of drugs in living systems has become key techniques in modern therapeutics.Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization.At the subcellular level,super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs.Moving beyond subcellular imaging,researchers have integrated multiple modes,like optical near-infrared II imaging,to study the complex spatiotemporal interactions between drugs and their surroundings.By combining these visualization approaches,researchers gain supplementary information on physiological parameters,metabolic activity,and tissue composition,leading to a comprehensive understanding of drug behavior.This review focuses on cutting-edge technologies in drug visualization,particularly fluorescence imaging,and the main types of fluorescent molecules used.Additionally,we discuss current challenges and prospects in targeted drug research,emphasizing the importance of multidisciplinary cooperation in advancing drug visualization.With the integration of advanced imaging technology and molecular design,drug visualization has the potential to redefine our understanding of pharmacology,enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.
基金The National Social Science Foundation of China(20BGL152)The General Project on the Protection,Inheritance and Promotion of the Yangtze River Culture in Hubei Province(HCYK2024Y09)。
文摘Rural tourism is an important means of comprehensively promoting the rural revitalisation of industry andpractising the concept of“two mountains theory”.Rural tourism transforms the resource advantages of rural areasinto economic advantages,but its development entails problems such as the unfair distribution of benefits,uncleardistribution mechanisms,and the non-standardised compensation of benefits.Therefore,finding a mode of governance of rural tourism that can effectively achieve sustainable development is an urgent issue that warrants attention.Taking Jukou Township in Fujian Province as a case,this study constructs a logical framework linking theEco-bank model and rural tourism governance and reveals the practicality and sustainability of rural tourism governance under the Eco-bank model.The study shows the following.(1)As a kind of innovative mechanism forachieving the transformation of resource value through the participation of multiple subjects,the Eco-bank modelsolves the development dilemma of rural tourism through the integration of decentralised resource managementrights,the establishment of property rights constraints and supervision mechanisms for the coordination of stakeholder interests,and the linkage and development of internal and external resources of the countryside.(2)JukouTownship has built a resource operation platform for“ancient house Eco-bank”based on ancient house resourcesand ecological tourism resources.The construction of a rural governance mechanism that combines village collectives,new township elites,villagers,high-end art operation units,and multiple institutional governance entities effectively converts idle ancient houses and high-quality ecological tourism resources into assets and funds to promote the development and growth of the rural collective economy while effectively promoting the stable and sustainable development of the cultural tourism industry in Jukou Township.
基金supported by the National Social Science Youth Foundation of China(Project No.20CGL014)the Social Science Planning Project in Chongqing,China(Project No.2021BS084)
文摘The governance effects of directors’and officers’liability insurance(D&O insurance),an important tool for risk diversification,are of strong concern in the capital market.Using a sample of Chinese A-share listed firms from2009 to 2018,we examine the impact of D&O insurance on excess corporate leverage.We find that D&O insurance is negatively associated with excess corporate leverage and that this result is consistent with a series of robustness tests.Further analyses show that D&O insurance impedes excess corporate leverage mainly because of its effect on external monitoring.The effect is more pronounced for firms that are state-owned,have political connections and are located in provinces with low marketization than for other firms.
基金financially supported by the project of lung cancer targeted therapy research of Beijing CSCO(No.Y-2021AST/qn-0013)the National Natural Science Foundation of China(No.82103343).
文摘Kirsten rat sarcoma(KRAS)mutant non-small cell lung cancer(NSCLC)has distinct co-mutational profiles.Approximately 20%of KRAS mutant NSCLC cases underwent loss-of-function mutation of Kelch-like ECH-associated protein 1(KEAP1)gene,namely KRAS-KEAP1 comutation(KK)type,which exhibited a poorer immune checkpoint inhibitor(ICl)response compared with individual KRAS mutation(K)type tumors.i Recent studies suggest that K-type tumors are referred to as"hot tumors"while KK-type tumors are as"cold tumors".Therefore,clarifying the molecular mechanism of the poor IClresponsive phenotype of KK-type tumors is the key to improving the clinical efficacy and breaking through the therapy bottleneck.Co-mutations could regulate the immune contexture to reshape the tumor immune microenvironment(TIME)。
基金supported by the National Natural Science Foundation of China[81672991 and 81874139 to S.L.,81872285 to Y.S.,81728014 to Y.T.,81672787 to Y.T.,81672307 to X.W,81772927 to D.X.]the National Basic Research Program of China[2015CB553903 to Y.T.]+1 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,No.111-2-12)the Fundamental Research Funds for the Central Universities[2017zzts206 to N.L.].
文摘Posttranslational modifications(PTMs)of proteins,including chromatin modifiers,play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties.However,the roles of Lymphoid-specific helicase(LSH),a DNA methylation modifier,in modulating stem-like properties in cancer are still not clearly clarified.Therefore,exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH.Here,we demonstrate that LSH is capable to undergo PTMs,including methylation and phosphorylation.The arginine methyltransferase PRMT5 can methylate LSH at R309 residue,meanwhile,LSH could as well be phosphorylated by MAPK1 kinase at S503 residue.We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue,which eventually promoting stem-like properties in lung cancer.Whereas,phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties,indicating the critical roles of LSH PTMs in modulating stem-like properties.Thus,our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.
