Bearingless switched reluctance motor(BSRM) not only combines the merits of bearingless motor(BM) and switched reluctance motor(SRM), but also decreases the vibration and acoustic noise of SRM, so it could be a strong...Bearingless switched reluctance motor(BSRM) not only combines the merits of bearingless motor(BM) and switched reluctance motor(SRM), but also decreases the vibration and acoustic noise of SRM, so it could be a strong candidate for high-speed driving fields. Under the circumstances, a 12/14 BSRM with hybrid stator pole has been proposed due to its high output torque density and excellent decoupling characteristics between torque and suspension force. However, this motor has torque dead-zone, which leads to problems of self-start at some rotor positions and large torque ripple during normal operation. To solve the existing problems in the 12/14 type, an asymmetric rotor pole type BSRM is proposed. The structure and design process of the proposed motor is presented in detail. The characteristics of the proposed motor is analyzed and compared with that of the 12/14 type. Furthermore, prototype of the proposed structure is designed, manufactured and experimented. Finally, simulation and test results are illustrated and analyzed to prove the validity of the proposed structure.展开更多
Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte proliferation.Indeed,Th17 cells and IL-17 play critical roles in...Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte proliferation.Indeed,Th17 cells and IL-17 play critical roles in the pathogenesis of psoriasis.The monoclonal antibodies against cytokines have been shown to have effectively immunosuppressive effects on human psoriasis.However,there are still some patients that have no response to these treatments.Some patients have even serious side-effects which may affect their life.Mesenchymal stem cells have the ability of immunosuppressive and anti-inflammatory effects,which may be an alternative therapy with more safety and efficacy for human psoriasis.Moreover,the underlying mechanisms by which the MSCs prevent or ameliorate psoriasis are still poorly understood.Here,we first isolated and characterized human adipose,placenta,and umbilical cord-derived mesenchymal stem cells(haMSCs,hpMSCs,and huMSCs).After that,the animal model of imiquimod(IMQ)-induced psoriasis in C57BL/6 mice was confirmed.We investigated the impact of haMSCs,hpMSCs,and huMSCs on this model by H&E staining,immunohistochemistry staining,and quantitative real-time PCR.Data analysis showed that mice subcutaneously injected with these MSCs had a significantly decreased epidermal thickness,which was caused by obviously reduced hyper-proliferation of keratinocytes.Furthermore,our findings revealed that the infiltration of T cells to psoriatic lesions in IMQ-induced psoriasis mice was markedly downregulated by intradermal administration of haMSCs,hpMSCs,and huMSCs,respectively.Consequently,the production of IL-17 from Th17 cells was reduced,which inhibits the proliferation of keratinocytes in lesioned skin of IMQ-induced psoriasis mice.These data suggest that haMSCs,hpMSCs,and huMSCs can inhibit the effects of proinflammatory Th17 cells on the development of psoriasis,which may be potential therapeutic candidates for skin inflammatory disease or other autoimmune diseases.展开更多
Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent st...Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.展开更多
基金supported by National Natural Science Foundation of China under Grant 52077141 and 51920105011Young and Middle-Aged Scientific and Technological Innovation Talent Program of Shenyang City of Liaoning Province of China under Grant RC200427。
文摘Bearingless switched reluctance motor(BSRM) not only combines the merits of bearingless motor(BM) and switched reluctance motor(SRM), but also decreases the vibration and acoustic noise of SRM, so it could be a strong candidate for high-speed driving fields. Under the circumstances, a 12/14 BSRM with hybrid stator pole has been proposed due to its high output torque density and excellent decoupling characteristics between torque and suspension force. However, this motor has torque dead-zone, which leads to problems of self-start at some rotor positions and large torque ripple during normal operation. To solve the existing problems in the 12/14 type, an asymmetric rotor pole type BSRM is proposed. The structure and design process of the proposed motor is presented in detail. The characteristics of the proposed motor is analyzed and compared with that of the 12/14 type. Furthermore, prototype of the proposed structure is designed, manufactured and experimented. Finally, simulation and test results are illustrated and analyzed to prove the validity of the proposed structure.
基金from the National Natural Science Foundation of China(No.81703118).
文摘Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte proliferation.Indeed,Th17 cells and IL-17 play critical roles in the pathogenesis of psoriasis.The monoclonal antibodies against cytokines have been shown to have effectively immunosuppressive effects on human psoriasis.However,there are still some patients that have no response to these treatments.Some patients have even serious side-effects which may affect their life.Mesenchymal stem cells have the ability of immunosuppressive and anti-inflammatory effects,which may be an alternative therapy with more safety and efficacy for human psoriasis.Moreover,the underlying mechanisms by which the MSCs prevent or ameliorate psoriasis are still poorly understood.Here,we first isolated and characterized human adipose,placenta,and umbilical cord-derived mesenchymal stem cells(haMSCs,hpMSCs,and huMSCs).After that,the animal model of imiquimod(IMQ)-induced psoriasis in C57BL/6 mice was confirmed.We investigated the impact of haMSCs,hpMSCs,and huMSCs on this model by H&E staining,immunohistochemistry staining,and quantitative real-time PCR.Data analysis showed that mice subcutaneously injected with these MSCs had a significantly decreased epidermal thickness,which was caused by obviously reduced hyper-proliferation of keratinocytes.Furthermore,our findings revealed that the infiltration of T cells to psoriatic lesions in IMQ-induced psoriasis mice was markedly downregulated by intradermal administration of haMSCs,hpMSCs,and huMSCs,respectively.Consequently,the production of IL-17 from Th17 cells was reduced,which inhibits the proliferation of keratinocytes in lesioned skin of IMQ-induced psoriasis mice.These data suggest that haMSCs,hpMSCs,and huMSCs can inhibit the effects of proinflammatory Th17 cells on the development of psoriasis,which may be potential therapeutic candidates for skin inflammatory disease or other autoimmune diseases.
基金This work is supported by grants from the National Natural Science Foundation of China(No.82070509,81930088,81725018)Innovative Research Team of High-Level Local Universities in Shanghai,and the Natural Science Foundation of Shanghai Science and Technology Committee,China(No.20ZR1447400).
文摘Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.