Objective Mitochondrial reactive oxygen species(mtROS)could cause damage to pancreaticβ-cells,rendering them susceptible to oxidative damage.Hence,investigating the potential of the mitochondriatargeted antioxidant(M...Objective Mitochondrial reactive oxygen species(mtROS)could cause damage to pancreaticβ-cells,rendering them susceptible to oxidative damage.Hence,investigating the potential of the mitochondriatargeted antioxidant(Mito-TEMPO)to protect pancreaticβ-cells from ferroptosis by mitigating lipid peroxidation becomes crucial.Methods MIN6 cells were cultured in vitro with 100μmol/L sodium palmitate(SP)to simulate diabetes.FerroOrange was utilized for the detection of Fe2+fluorescence staining,BODIPY581/591C11 for lipid reactive oxygen species,and MitoSox-Red for mtROS.Alterations in mitophagy levels were assessed through the co-localization of lysosomal and mitochondrial fluorescence.Western blotting was employed to quantify protein levels of Acsl4,GPX4,FSP1,FE,PINK1,Parkin,TOMM20,P62,and LC3.Subsequently,interventions were implemented using Mito-TEMPO and Carbonyl cyanide 3-chlorophenylhydrazone(CCCP)to observe changes in ferroptosis and mitophagy within MIN6 cells.Results We found that SP induced a dose-dependent increase in Fe2+and lipid ROS in MIN6 cells while decreasing the expression levels of GPX4 and FSP1 proteins.Through bioinformatics analysis,it has been uncovered that mitophagy assumes a crucial role within the ferroptosis pathway associated with diabetes.Additionally,SP decreased the expression of mitophagy-related proteins PINK1 and Parkin,leading to mtROS overproduction.Conversely,Mito-TEMPO effectively eliminated mtROS while activating the mitophagy pathways involving PINK1 and Parkin,thereby reducing the occurrence of ferroptosis in MIN6 cells.CCCP also demonstrated efficacy in reducing ferroptosis in MIN6 cells.Conclusion In summary,Mito-TEMPO proved effective in attenuating mtROS production and initiating mitophagy pathways mediated by PINK1 and Parkin in MIN6 cells.Consequently,this decreased iron overload and lipid peroxidation,ultimately safeguarding the cells from ferroptosis.展开更多
A variety of problems in operations research, performance analysis, manufacturing, and communication networks, etc., can be modelled as discrete event systems with minimum and maximum constraints. When such systems re...A variety of problems in operations research, performance analysis, manufacturing, and communication networks, etc., can be modelled as discrete event systems with minimum and maximum constraints. When such systems require only maximum constraints （or dually, only minimum constraints）, they can be studied using linear methods based on max-plus algebra. Systems with mixed constraints are called min-max systems in which rain, max and addition operations appear simultaneously. A significant amount of work on such systems can be seen in literature. In this paper we provide some new results with regard to the balance problem of min-max functions; these are the structure properties of min-max systems. We use these results in the structural stabilization. Our main results are two sufficient conditions for the balance and one sufficient condition for the structural stabilization. The block technique is used to analyse the structure of the systems. The proposed methods, based on directed graph and max-plus algebra are constructive in nature. We provide several examples to demonstrate how the methods work in practice.展开更多
基金supported by a grant from the Science and Technology Tackling Programme Project of Xinjiang Production and Construction Corps(2021AB030).
文摘Objective Mitochondrial reactive oxygen species(mtROS)could cause damage to pancreaticβ-cells,rendering them susceptible to oxidative damage.Hence,investigating the potential of the mitochondriatargeted antioxidant(Mito-TEMPO)to protect pancreaticβ-cells from ferroptosis by mitigating lipid peroxidation becomes crucial.Methods MIN6 cells were cultured in vitro with 100μmol/L sodium palmitate(SP)to simulate diabetes.FerroOrange was utilized for the detection of Fe2+fluorescence staining,BODIPY581/591C11 for lipid reactive oxygen species,and MitoSox-Red for mtROS.Alterations in mitophagy levels were assessed through the co-localization of lysosomal and mitochondrial fluorescence.Western blotting was employed to quantify protein levels of Acsl4,GPX4,FSP1,FE,PINK1,Parkin,TOMM20,P62,and LC3.Subsequently,interventions were implemented using Mito-TEMPO and Carbonyl cyanide 3-chlorophenylhydrazone(CCCP)to observe changes in ferroptosis and mitophagy within MIN6 cells.Results We found that SP induced a dose-dependent increase in Fe2+and lipid ROS in MIN6 cells while decreasing the expression levels of GPX4 and FSP1 proteins.Through bioinformatics analysis,it has been uncovered that mitophagy assumes a crucial role within the ferroptosis pathway associated with diabetes.Additionally,SP decreased the expression of mitophagy-related proteins PINK1 and Parkin,leading to mtROS overproduction.Conversely,Mito-TEMPO effectively eliminated mtROS while activating the mitophagy pathways involving PINK1 and Parkin,thereby reducing the occurrence of ferroptosis in MIN6 cells.CCCP also demonstrated efficacy in reducing ferroptosis in MIN6 cells.Conclusion In summary,Mito-TEMPO proved effective in attenuating mtROS production and initiating mitophagy pathways mediated by PINK1 and Parkin in MIN6 cells.Consequently,this decreased iron overload and lipid peroxidation,ultimately safeguarding the cells from ferroptosis.
基金This work was supported by National Natural Science of China (No.69874040) the National Key Project of China, and the Hundred Talents Program of the Chinese Academy of Sciences.
文摘A variety of problems in operations research, performance analysis, manufacturing, and communication networks, etc., can be modelled as discrete event systems with minimum and maximum constraints. When such systems require only maximum constraints （or dually, only minimum constraints）, they can be studied using linear methods based on max-plus algebra. Systems with mixed constraints are called min-max systems in which rain, max and addition operations appear simultaneously. A significant amount of work on such systems can be seen in literature. In this paper we provide some new results with regard to the balance problem of min-max functions; these are the structure properties of min-max systems. We use these results in the structural stabilization. Our main results are two sufficient conditions for the balance and one sufficient condition for the structural stabilization. The block technique is used to analyse the structure of the systems. The proposed methods, based on directed graph and max-plus algebra are constructive in nature. We provide several examples to demonstrate how the methods work in practice.
