Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic r...Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.展开更多
The Brushless DC Motor drive systems are used widely with renewable energy resources.The power converter controlling technique increases the performance by novel techniques and algorithms.Conventional approaches are m...The Brushless DC Motor drive systems are used widely with renewable energy resources.The power converter controlling technique increases the performance by novel techniques and algorithms.Conventional approaches are mostly focused on buck converter,Fuzzy logic control with various switching activity.In this proposed research work,the QPSO(Quantum Particle Swarm Optimization algorithm)is used on the switching state of converter from the generation unit of solar module.Through the duty cycle pulse from optimization function,the MOSFET(Metal-Oxide-Semiconductor Field-Effect Transistor)of the Boost converter gets switched when BLDC(Brushless Direct Current Motor)motor drive system requires power.Voltage Source three phase inverter and Boost converter is controlled by proportional-integral(PI)controller.Based on the BLDC drive,the load utilized from the solar generating module.Experimental results analyzed every module of the proposed grid system,which are solar generation utilizes the irradiance and temperature depends on this the Photovoltaics(PV)power is generated and the QPSO with Duty cycle switching state is determined.The Boost converter module is boost stage based on generation and load is obtained.Single Ended Primary Inductor Converter(SEPIC)and Zeta converter model is compared with the proposed logic;the proposed boost converter achieves the results.Three phase inverter control,PI,and BLDC motor drive results.Thus the proposed grid model is constructed to obtain the better performance results than most recent literatures.Overall design model is done by using MATLAB/Simulink 2020a.展开更多
基金funded by the National Natural Science Foundation of China(No.81770126,No.81900160,No.81800163,No.22025702,and No.91853203)the Fujian Natural Science Foundation of China(No.2020J011246 and No.2021J011359)+2 种基金the Foundation of Health and Family Planning Commission of Fujian Province of China(No.2020GGB054)the Xiamen Municipal Bureau of Science and Technology(No.3502Z20209003)the Fundamental Research Funds for the Central Universities of China(No.20720190101).
文摘Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.
文摘The Brushless DC Motor drive systems are used widely with renewable energy resources.The power converter controlling technique increases the performance by novel techniques and algorithms.Conventional approaches are mostly focused on buck converter,Fuzzy logic control with various switching activity.In this proposed research work,the QPSO(Quantum Particle Swarm Optimization algorithm)is used on the switching state of converter from the generation unit of solar module.Through the duty cycle pulse from optimization function,the MOSFET(Metal-Oxide-Semiconductor Field-Effect Transistor)of the Boost converter gets switched when BLDC(Brushless Direct Current Motor)motor drive system requires power.Voltage Source three phase inverter and Boost converter is controlled by proportional-integral(PI)controller.Based on the BLDC drive,the load utilized from the solar generating module.Experimental results analyzed every module of the proposed grid system,which are solar generation utilizes the irradiance and temperature depends on this the Photovoltaics(PV)power is generated and the QPSO with Duty cycle switching state is determined.The Boost converter module is boost stage based on generation and load is obtained.Single Ended Primary Inductor Converter(SEPIC)and Zeta converter model is compared with the proposed logic;the proposed boost converter achieves the results.Three phase inverter control,PI,and BLDC motor drive results.Thus the proposed grid model is constructed to obtain the better performance results than most recent literatures.Overall design model is done by using MATLAB/Simulink 2020a.
