Fuzzy control problems for systems with bounded uncertain delays were studied. Based on Lyapunov stability theory and matrix theory, a nonlinear state feedback fuzzy controller was designed by linear matrix inequaliti...Fuzzy control problems for systems with bounded uncertain delays were studied. Based on Lyapunov stability theory and matrix theory, a nonlinear state feedback fuzzy controller was designed by linear matrix inequalities （LMI） approach, and the global exponential stability of the closed-loop system was strictly proved. For a fuzzy control system with bounded uncertain delays, under the global exponential stability condition which is reduced to p linear matrix inequalities, the controller guarantees stability performances of state variables. Finally, the simulation shows the validity of the method in tiffs paper.展开更多
Purpose:Approximately 1/3 of brain tumors are gliomas.Previous glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma deve...Purpose:Approximately 1/3 of brain tumors are gliomas.Previous glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma development remain unclear.Methods:Nanoscale liquid chromatography coupled with tandem mass spectrometry(nano LC-MS/MS)and RNA sequencing were used to identify diferential protein and mRNA expression in clinical glioma samples.Quantitative real-time PCR(qRT-PCR)was used to measure the expression of POSTN in tissues and cells.The efects of POSTN on glioma cell migration and invasion were examined using wound healing,Transwell,and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in vivo.The efects of POSTN on the stability,endocytosis,and degradation of EGFR were examined by immunoblotting and immunofuorescence staining.Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR.Immunohistochemical staining was carried out to confrm the clinical signifcance of POSTN.Results:Overexpression of POSTN induced epithelial-to-mesenchymal transition(EMT)in glioma cells in vivo and in vitro.Mechanistically,POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation.In addition,POSTN was found to bind to EGFR and RIN1,inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway.Conclusion:These fndings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation,resulting in glioma cell EMT through the PI3K-AKT signaling pathway.Targeting POSTN/EGFR/RIN1 interactions may guarantee benefcial outcomes of glioma treatment.展开更多
Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired ...Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM)due to overexpression of programmed death ligand 1(PD-L1)on the surface of cancer cell membrane.To improve the immunotherapeutic performance of CDK4/6i,we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo.We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs),and elicited protective immune response and efficiently suppressed tumor growth in vivo.This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery,which might provide a novel insight for RNAi-based cancer immunotherapy.展开更多
文摘Fuzzy control problems for systems with bounded uncertain delays were studied. Based on Lyapunov stability theory and matrix theory, a nonlinear state feedback fuzzy controller was designed by linear matrix inequalities （LMI） approach, and the global exponential stability of the closed-loop system was strictly proved. For a fuzzy control system with bounded uncertain delays, under the global exponential stability condition which is reduced to p linear matrix inequalities, the controller guarantees stability performances of state variables. Finally, the simulation shows the validity of the method in tiffs paper.
基金supported by grants from National Natural Science Foundation of China (81772682)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
文摘Purpose:Approximately 1/3 of brain tumors are gliomas.Previous glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma development remain unclear.Methods:Nanoscale liquid chromatography coupled with tandem mass spectrometry(nano LC-MS/MS)and RNA sequencing were used to identify diferential protein and mRNA expression in clinical glioma samples.Quantitative real-time PCR(qRT-PCR)was used to measure the expression of POSTN in tissues and cells.The efects of POSTN on glioma cell migration and invasion were examined using wound healing,Transwell,and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in vivo.The efects of POSTN on the stability,endocytosis,and degradation of EGFR were examined by immunoblotting and immunofuorescence staining.Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR.Immunohistochemical staining was carried out to confrm the clinical signifcance of POSTN.Results:Overexpression of POSTN induced epithelial-to-mesenchymal transition(EMT)in glioma cells in vivo and in vitro.Mechanistically,POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation.In addition,POSTN was found to bind to EGFR and RIN1,inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway.Conclusion:These fndings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation,resulting in glioma cell EMT through the PI3K-AKT signaling pathway.Targeting POSTN/EGFR/RIN1 interactions may guarantee benefcial outcomes of glioma treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.51873228 and 31671024)Basic Research Program of Shenzhen(No.JCYJ20180227175420974)+1 种基金Science and Technology Development Fund,Macao SAR(No.083/2017/A2)Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences。
文摘Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM)due to overexpression of programmed death ligand 1(PD-L1)on the surface of cancer cell membrane.To improve the immunotherapeutic performance of CDK4/6i,we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo.We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs),and elicited protective immune response and efficiently suppressed tumor growth in vivo.This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery,which might provide a novel insight for RNAi-based cancer immunotherapy.
