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 fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or offtarget effects.Recently,the fast accumulation of gen...A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or offtarget effects.Recently,the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology.Here,we propose a novel Siamese spectral-based graph convolutional network(SSGCN)model for inferring the protein targets of chemical compounds from gene transcriptional profiles.Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets,and the biological networks under different experiment conditions further complicate the situation,the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles.On a benchmark set and a large time-split validation dataset,the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map.Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound,or reversely,in finding novel inhibitors of a given target of interest.展开更多
Rare earth(RE) pentaborates,both α-and β-polymorphs,are good candidates for photoluminescent hosts suitable for various RE activators,Ce^(3+) acts not only as an activator itself,but also as a sensitizer to other ra...Rare earth(RE) pentaborates,both α-and β-polymorphs,are good candidates for photoluminescent hosts suitable for various RE activators,Ce^(3+) acts not only as an activator itself,but also as a sensitizer to other rare earth activators,like in the case of commercial green phosphor CeMgAl_(11)O_(19):Tb^(3+).In this work,two solid solutions of β-La_(0.9-x)Ce_(0.1)Tb_(x)B_(5)O_(9)(0≤x≤0.15) and β-La_(0.9-y)Ce_(0.1)Dy_(y)B_(5)O_(9)(0≤y≤0.07)were prepared by sol-gel method with high crystallinity,and the phase purity was confirmed with careful analyses on powder X-ray diffraction patterns.Energy transfers are expected due to the overlapping of Ce^(3+)emission with the Tb^(3+)/Dy^(3+)excitation.Indeed,the steady photoluminescence spectra indicate the decrease of the Ce^(3+)emission and the increase of the Tb^(3+)/Dy^(3+) emission,and the fluorescence decay curves exhibit the decrease of the average lifetime of Ce^(3+).The energy transfer efficiency is estimated to be 60% at χ=0.15 and 55% at y=0.07,respectively.The mechanism is likely through the dipole-dipole electric interactions for both cases.With this rationale,the Tb^(3+)and Dy^(3+)emissions are greatly enhanced,in particular,the white emission of Dy^(3+)in β-La_(0.85)Ce_(0.1)Dy_(0.05)B_(5)O_(9) is enhanced by 20 times.展开更多
To the Editor:ADP-ribosylation factor 1 (ARF1) plays a critical role in regulating vesicle formation and transport1. The dysregulation of ARF1 expression and/or activity is involved in many human cancers, such as brea...To the Editor:ADP-ribosylation factor 1 (ARF1) plays a critical role in regulating vesicle formation and transport1. The dysregulation of ARF1 expression and/or activity is involved in many human cancers, such as breast cancer2,3. Therefore, ARF1 is one of the promising therapeutic targets for cancer treatment.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.
文摘A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or offtarget effects.Recently,the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology.Here,we propose a novel Siamese spectral-based graph convolutional network(SSGCN)model for inferring the protein targets of chemical compounds from gene transcriptional profiles.Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets,and the biological networks under different experiment conditions further complicate the situation,the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles.On a benchmark set and a large time-split validation dataset,the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map.Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound,or reversely,in finding novel inhibitors of a given target of interest.
基金Project supported by the National Natural Science Foundation of China (21771027,21671028,21805020)Natural Science Foundation of Chongqing (cstc2019jcyj-msxmX0330)。
文摘Rare earth(RE) pentaborates,both α-and β-polymorphs,are good candidates for photoluminescent hosts suitable for various RE activators,Ce^(3+) acts not only as an activator itself,but also as a sensitizer to other rare earth activators,like in the case of commercial green phosphor CeMgAl_(11)O_(19):Tb^(3+).In this work,two solid solutions of β-La_(0.9-x)Ce_(0.1)Tb_(x)B_(5)O_(9)(0≤x≤0.15) and β-La_(0.9-y)Ce_(0.1)Dy_(y)B_(5)O_(9)(0≤y≤0.07)were prepared by sol-gel method with high crystallinity,and the phase purity was confirmed with careful analyses on powder X-ray diffraction patterns.Energy transfers are expected due to the overlapping of Ce^(3+)emission with the Tb^(3+)/Dy^(3+)excitation.Indeed,the steady photoluminescence spectra indicate the decrease of the Ce^(3+)emission and the increase of the Tb^(3+)/Dy^(3+) emission,and the fluorescence decay curves exhibit the decrease of the average lifetime of Ce^(3+).The energy transfer efficiency is estimated to be 60% at χ=0.15 and 55% at y=0.07,respectively.The mechanism is likely through the dipole-dipole electric interactions for both cases.With this rationale,the Tb^(3+)and Dy^(3+)emissions are greatly enhanced,in particular,the white emission of Dy^(3+)in β-La_(0.85)Ce_(0.1)Dy_(0.05)B_(5)O_(9) is enhanced by 20 times.
基金supported by the National Natural Science Foundation of China (81903639 to Sulin Zhang,China)Lingang Laboratory (LG202102-01-02 to Mingyue Zheng,China,LG-QS-202204-01 to Sulin Zhang,China)+1 种基金Shanghai Municipal Science and Technology Major Project (Hualiang Jiang,China)Shanghai Sailing Program (19YF1457800 to Sulin Zhang,China)。
文摘To the Editor:ADP-ribosylation factor 1 (ARF1) plays a critical role in regulating vesicle formation and transport1. The dysregulation of ARF1 expression and/or activity is involved in many human cancers, such as breast cancer2,3. Therefore, ARF1 is one of the promising therapeutic targets for cancer treatment.
