Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh...Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.展开更多
Based on the theoretical representation of piezoelectric quasicrystal,a generalized dynamic model is built to represent the transmission of wave aspects in surface acoustic pulse nano-devices.Surface elasticity,surfac...Based on the theoretical representation of piezoelectric quasicrystal,a generalized dynamic model is built to represent the transmission of wave aspects in surface acoustic pulse nano-devices.Surface elasticity,surface piezoelectricity,and surface permittivity help to include the surface effect,which equals additional thin sheets.It is shown that,under certain assumptions,this generalized dynamic model may be simplified to a few classical examples that are appropriate for both macro and nano-scale applications.In the current work,surface piezoelectricity is used to develop a theoretical model for shear horizontal(SH)waves where it contains the surface piezoelectricity theory and a linear spring model to quantitatively and qualitatively explore SH waves in an orthotropic piezoelectric quasicrystal layer overlying an elastic framework(Model I),a piezoelectric quasi-crystal nano substrate,and an orthotropic piezoelectric quasicrystal half-space(Model II).The theoretical model stimulates the numerical results,which establish the critical thickness.As the piezoelectric layer’s thickness gets closer to nanometres,surface energy must be included when analyzing dispersion properties.Furthermore,the effects of surface elasticity and density on wave velocity are investigated individually.The authors establish a parameter,precisely the ratio of the physical modulus along the width direction to along the direction of wave travel.The surface effect’s impact on the general char-acteristics of piezoelectric structures is seen as a spring force acting on bulk boundaries.Analytical presentation of frequency equations for both symmetric and anti-symmetric waves pertains to the case of an electrical short circuit in Model II.The project aims to analyze SH waves in orthogonal anisotropic,transversely isotropic piezoelectric layered nanostructures,providing a practical mathematical tool for surface effects analysis and adaptability to other wave types,including Rayleigh waves and acoustic surface waves.展开更多
基金supported by research grants from the Ministry of Science and Technology(MOST 108-2314-B-400-026 and 109-2013-B-400-036)National Science and Technology Council(NSTC 112-2320-B-214-010 and 113-2320-B-214-002)+1 种基金I-Shou University(ISU-112-01-12A,ISU112-S-02 and ISU114-S-04)National Health Research Institutes,Taiwan(CA-111-PP-19).
文摘Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.
文摘Based on the theoretical representation of piezoelectric quasicrystal,a generalized dynamic model is built to represent the transmission of wave aspects in surface acoustic pulse nano-devices.Surface elasticity,surface piezoelectricity,and surface permittivity help to include the surface effect,which equals additional thin sheets.It is shown that,under certain assumptions,this generalized dynamic model may be simplified to a few classical examples that are appropriate for both macro and nano-scale applications.In the current work,surface piezoelectricity is used to develop a theoretical model for shear horizontal(SH)waves where it contains the surface piezoelectricity theory and a linear spring model to quantitatively and qualitatively explore SH waves in an orthotropic piezoelectric quasicrystal layer overlying an elastic framework(Model I),a piezoelectric quasi-crystal nano substrate,and an orthotropic piezoelectric quasicrystal half-space(Model II).The theoretical model stimulates the numerical results,which establish the critical thickness.As the piezoelectric layer’s thickness gets closer to nanometres,surface energy must be included when analyzing dispersion properties.Furthermore,the effects of surface elasticity and density on wave velocity are investigated individually.The authors establish a parameter,precisely the ratio of the physical modulus along the width direction to along the direction of wave travel.The surface effect’s impact on the general char-acteristics of piezoelectric structures is seen as a spring force acting on bulk boundaries.Analytical presentation of frequency equations for both symmetric and anti-symmetric waves pertains to the case of an electrical short circuit in Model II.The project aims to analyze SH waves in orthogonal anisotropic,transversely isotropic piezoelectric layered nanostructures,providing a practical mathematical tool for surface effects analysis and adaptability to other wave types,including Rayleigh waves and acoustic surface waves.
