Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to ...Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.展开更多
Nitrogen(N)deposition is a significant aspect of global change and poses a threat to terrestrial biodiversity.The impact of plant-soil microbe relationships to N deposition has recently attracted considerable attentio...Nitrogen(N)deposition is a significant aspect of global change and poses a threat to terrestrial biodiversity.The impact of plant-soil microbe relationships to N deposition has recently attracted considerable attention.Soil microorganisms have been proven to provide nutrients for specific plant growth,especially in nutrient-poor desert steppe ecosystems.However,the effects of N deposition on plant-soil microbial community interactions in such ecosystems remain poorly understood.To investigate these effects,we conducted a 6-year N-addition field experiment in a Stipa breviflora Griseb.desert steppe in Inner Mongolia Autonomous Region,China.Four N treatment levels(N0,N30,N50,and N100,corresponding to 0,30,50,and 100 kg N/(hm2•a),respectively)were applied to simulate atmospheric N deposition.The results showed that N deposition did not significantly affect the aboveground biomass of desert steppe plants.N deposition did not significantly reduce the alfa-diversity of plant and microbial communities in the desert steppe,and low and mediate N additions(N30 and N50)had a promoting effect on them.The variation pattern of plant Shannon index was consistent with that of the soil bacterial Chao1 index.N deposition significantly affected the beta-diversity of plants and soil bacteria,but did not significantly affect fungal communities.In conclusion,N deposition led to co-evolution between desert steppe plants and soil bacterial communities,while fungal communities exhibited strong stability and did not undergo significant changes.These findings help clarify atmospheric N deposition effects on the ecological health and function of the desert steppe.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
Photodynamic therapy(PDT)has emerged as a novel therapeutic modality for cancer treatment,but its therapeutic efficacy is severely limited by the hypoxic tumor microenvironment(TME).Here we designed an innovative mult...Photodynamic therapy(PDT)has emerged as a novel therapeutic modality for cancer treatment,but its therapeutic efficacy is severely limited by the hypoxic tumor microenvironment(TME).Here we designed an innovative multifunctional nano-platform which consists of a hollow MnO_(2) shell and internal photosensitizer IR780.It is not only used for multimodal imaging of oral squamous cell carcinoma(OSCC),but also for adjustment hypoxic TME to enhance cancer treatment.Hollow MnO_(2) can promote decomposition of tumor endogenous H2O2 to relieve tumor hypoxia,thereby enhancing the effect of photodynamic therapy.Photosensitizer IR780 generates singlet oxygen under laser irradiation to kill tumor cells,playing photodynamic effect,can also act as the contrast agents for photoacoustic and fluorescence multiple imaging,providing potential imaging capability for cancer therapeutic guidance and monitoring.Our research results in this article show that HMnO_(2)-IR780 nanocomposite exhibits good biocompatibility and nontoxicity,strong PA/FL imaging contrast,excellent oxygen production capacity and outstanding photodynamic therapy effect.This finding provides a new idea for multimodal imaging-guided nanotherapy for OSCC.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81974132,81770927Hunan Provincial Health Commission,No.20220702839+1 种基金the Natural Science Foundation of Hunan Province of China,No.2022JJ30076National Key R&D Program of China,No.2021YFA1101202(all to WS)。
文摘Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.
基金the National Natural Science Foundation of China(31860136,31560156)the Basic Scientific Research Service Fee Project of Colleges and Universities of Inner Mongolia Autonomous Regionthe Graduate Scientific Research Innovation Project of Inner Mongolia Autonomous Region(B20210158Z).
文摘Nitrogen(N)deposition is a significant aspect of global change and poses a threat to terrestrial biodiversity.The impact of plant-soil microbe relationships to N deposition has recently attracted considerable attention.Soil microorganisms have been proven to provide nutrients for specific plant growth,especially in nutrient-poor desert steppe ecosystems.However,the effects of N deposition on plant-soil microbial community interactions in such ecosystems remain poorly understood.To investigate these effects,we conducted a 6-year N-addition field experiment in a Stipa breviflora Griseb.desert steppe in Inner Mongolia Autonomous Region,China.Four N treatment levels(N0,N30,N50,and N100,corresponding to 0,30,50,and 100 kg N/(hm2•a),respectively)were applied to simulate atmospheric N deposition.The results showed that N deposition did not significantly affect the aboveground biomass of desert steppe plants.N deposition did not significantly reduce the alfa-diversity of plant and microbial communities in the desert steppe,and low and mediate N additions(N30 and N50)had a promoting effect on them.The variation pattern of plant Shannon index was consistent with that of the soil bacterial Chao1 index.N deposition significantly affected the beta-diversity of plants and soil bacteria,but did not significantly affect fungal communities.In conclusion,N deposition led to co-evolution between desert steppe plants and soil bacterial communities,while fungal communities exhibited strong stability and did not undergo significant changes.These findings help clarify atmospheric N deposition effects on the ecological health and function of the desert steppe.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
基金The present study was funded by the Chongqing Social Livelihood Science and Technology Innovation Project(Grant No.cstc2016shmszx00010)the Science and Technology Research Project of Chongqing Education Commission(Grant No.KJ1600231)the Program for Innovation Team Building at Institutions of Higher Education in Chongqing(Grant No.CXTDG201602006).
文摘Photodynamic therapy(PDT)has emerged as a novel therapeutic modality for cancer treatment,but its therapeutic efficacy is severely limited by the hypoxic tumor microenvironment(TME).Here we designed an innovative multifunctional nano-platform which consists of a hollow MnO_(2) shell and internal photosensitizer IR780.It is not only used for multimodal imaging of oral squamous cell carcinoma(OSCC),but also for adjustment hypoxic TME to enhance cancer treatment.Hollow MnO_(2) can promote decomposition of tumor endogenous H2O2 to relieve tumor hypoxia,thereby enhancing the effect of photodynamic therapy.Photosensitizer IR780 generates singlet oxygen under laser irradiation to kill tumor cells,playing photodynamic effect,can also act as the contrast agents for photoacoustic and fluorescence multiple imaging,providing potential imaging capability for cancer therapeutic guidance and monitoring.Our research results in this article show that HMnO_(2)-IR780 nanocomposite exhibits good biocompatibility and nontoxicity,strong PA/FL imaging contrast,excellent oxygen production capacity and outstanding photodynamic therapy effect.This finding provides a new idea for multimodal imaging-guided nanotherapy for OSCC.
