Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that ...Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis,contributing to a range of neurocellular dysfunctions.Pyroptosis,a recently identified form of programmed cell death,is characterized by caspase-1 activation and the action of the Gasdermin D(GSDMD)protein family,leading to cell perforation and inflammatory death.Methods In this study,human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide(H_(2)S)against this toxicity through the antagonization of pyroptosis.We employed CCK-8 and LDH assays to assess cell viability.YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability.Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells,that are mitigated by the H_(2)S donor NaHS.Furthermore,ATP was found to promote the activation of the NOD-like receptor pyrin domain-containing 1(NLRP-1),caspase-1,and the cleavage of GSDMD,with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1,caspase-1,and GSDMD pathway.展开更多
This study proposed a new and more flexible S-shaped rock damage evolution model from a phenomenological perspective based on an improved Logistic function to describe the characteristics of the rock strain softening ...This study proposed a new and more flexible S-shaped rock damage evolution model from a phenomenological perspective based on an improved Logistic function to describe the characteristics of the rock strain softening and damage process.Simultaneously,it established a constitutive model capable of describing the entire process of rock pre-peak compaction and post-peak strain softening deformation,considering the nonlinear effects of the initial compaction stage of rocks,combined with damage mechanics theory and effective medium theory.In addition,this research verified the rationality of the constructed damage constitutive model using results from uniaxial and conventional triaxial compression tests on Miluo granite,yellow sandstone,mudstone,and glutenite.The results indicate that based on the improved Logistic function,the theoretical damage model accurately describes the entire evolution of damage characteristics during rock compression deformation,from maintenance through gradual onset,accelerated development to deceleration and termination,in a simple and unified expression.At the same time,the constructed constitutive model can accurately simulate the stress-strain process of different rock types under uniaxial and conventional triaxial compression,and the theoretical model curve closely aligns with experimental data.Compared to existing constitutive models,the proposed model has significant advantages.The damage model parameters a,r and β have clear physical meanings and interact competitively,where the three parameters collectively determine the shape of the theoretical stress−strain curve.展开更多
文摘Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis,contributing to a range of neurocellular dysfunctions.Pyroptosis,a recently identified form of programmed cell death,is characterized by caspase-1 activation and the action of the Gasdermin D(GSDMD)protein family,leading to cell perforation and inflammatory death.Methods In this study,human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide(H_(2)S)against this toxicity through the antagonization of pyroptosis.We employed CCK-8 and LDH assays to assess cell viability.YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability.Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells,that are mitigated by the H_(2)S donor NaHS.Furthermore,ATP was found to promote the activation of the NOD-like receptor pyrin domain-containing 1(NLRP-1),caspase-1,and the cleavage of GSDMD,with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1,caspase-1,and GSDMD pathway.
基金Project(52074299)supported by the National Natural Science Foundation of ChinaProjects(2023JCCXSB02,BBJ2024083)supported by the Fundamental Research Funds for the Central Universities,China。
文摘This study proposed a new and more flexible S-shaped rock damage evolution model from a phenomenological perspective based on an improved Logistic function to describe the characteristics of the rock strain softening and damage process.Simultaneously,it established a constitutive model capable of describing the entire process of rock pre-peak compaction and post-peak strain softening deformation,considering the nonlinear effects of the initial compaction stage of rocks,combined with damage mechanics theory and effective medium theory.In addition,this research verified the rationality of the constructed damage constitutive model using results from uniaxial and conventional triaxial compression tests on Miluo granite,yellow sandstone,mudstone,and glutenite.The results indicate that based on the improved Logistic function,the theoretical damage model accurately describes the entire evolution of damage characteristics during rock compression deformation,from maintenance through gradual onset,accelerated development to deceleration and termination,in a simple and unified expression.At the same time,the constructed constitutive model can accurately simulate the stress-strain process of different rock types under uniaxial and conventional triaxial compression,and the theoretical model curve closely aligns with experimental data.Compared to existing constitutive models,the proposed model has significant advantages.The damage model parameters a,r and β have clear physical meanings and interact competitively,where the three parameters collectively determine the shape of the theoretical stress−strain curve.
