FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disea...FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P] on experimental autoimmune encephalomyelitis (EAE) in rats and mice. Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4^+ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and (S)-FTY720-P. When FTY720 or (S)-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4^+ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4^+ T cells into the inflammation site. Cellular & Molecular Immunology. 2005;2(6):439-448.展开更多
Background Methanesulfonic acid sodium salt (Dipyrone), an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of t...Background Methanesulfonic acid sodium salt (Dipyrone), an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle (V), methanesulfonic acid sodium salt (D), light damage model plus vehicle (MV) and light damage model plus methanesulfonic acid sodium salt (MD) groups (n=25 each). In the MD group, methanesulfonic acid sodium salt (100 mg/kg) was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy (TEM) were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I^m from the optic nerve. Electroretinography (ERG) test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c (CytC) and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group (P 〈0.05). TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 (Apaf-1), caspase 3, p53, p53-upregulated modulator of apoptosis (PUMA), Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.展开更多
This paper introduces the new notion of ( p +0) summable operator. It is shown that this property is stable under small perturbation by selfadjoint operators.
Carbon nanotubes(CNTs)are emerging as promising platforms for organic thermoelectric(TE)materials.However,the poor stability of n-doped states often presents a problem for the long-term operation of p-n junction TE mo...Carbon nanotubes(CNTs)are emerging as promising platforms for organic thermoelectric(TE)materials.However,the poor stability of n-doped states often presents a problem for the long-term operation of p-n junction TE modules.In this study,we synthesized a cross-linked organic superbase,2TBD-C10,as a dopant to create n-type CNTs that are resistant to air,heat,and humidity.When comparing the stability of 2TBD-C10-doped CNTs with those doped by a conventional superbase(TBD),we found that the enhanced stability could be attributed to the unique molecular structure of 2TBD-C10.This structure aids in effective adsorption on the CNT surfaces through multiple points,reduces volatility because of increased molecular weight,and suppresses water adsorption owing to the presence of hydrophobic alkyl chains.The results of our study demonstrate that tailoring the primary molecular structures of dopants can remarkably improve the stability of doped states in CNTs.The stable n-type materials were integrated into all-CNT TE modules,achieving good-to-excellent performance(power output of approximately 35μW from a temperature difference of approximately 65°C),making them suitable for powering wireless sensors and green light-emitting diodes.展开更多
Transition metal chalcogenides(TMCs)are extensively employed as cathode materials for rechargeable aluminum batteries(RABs)due to their high theoretical specific capacity and voltage plateau.Although promising,practic...Transition metal chalcogenides(TMCs)are extensively employed as cathode materials for rechargeable aluminum batteries(RABs)due to their high theoretical specific capacity and voltage plateau.Although promising,practical applications are hindered by challenges such as inferior structural stability,slow reaction kinetics,and inadequate electronic conductivity.Herein,Mn-ion doping engineering and g-C_(3)N_(4) etched porous carbon frameworks(Mn-ZnSe@CNPC)were integrated to synergistically enhance the electrochemical properties of ZnSe.Through modulating the d-and p-band centers and regulating electronic interactions,Mn-ion doping enhances adsorption for solvent groups and reduces electron transfer energy barriers,resulting in Mn-ZnSe@CNPC cathodes with high redox activity and fast reaction kinetics.In addition,the porous carbon nanocages act as support frameworks,preventing the agglomeration of ZnSe nanoparticles and providing ample ion transport channels,thus addressing issues related to poor cyclability and slow electrochemical kinetics in RABs.Benefiting from the d–p orbital modulation strategy and structural advantages,the tailored Mn-ZnSe@CNPC cathode exhibits boosted electrochemical performance and excellent stability.展开更多
P2-type Na-NiMn oxides have garnered significant attention for sodium-ion batteries owing to their excellent rate capability.However,they are adversely affected by the harmful P2-O2 phase transitions,which cause subst...P2-type Na-NiMn oxides have garnered significant attention for sodium-ion batteries owing to their excellent rate capability.However,they are adversely affected by the harmful P2-O2 phase transitions,which cause substantial capacity degradation and poor cycling performance.In this work,a unique P2(84%)/O3(16%)biphasic layered oxide,Na_(0.76)Ni_(0.22)Mg_(0.11)Mn_(0.57)Ti_(0.1)O_(2)(NNMMT),is successfully designed and synthesized by a Mg/Ti co-doping strategy.The doping of Mg and Ti can form stable O-TM-O bonds,while the biphasic structure generates distinctive interlocked interfaces at the boundaries.The harmful phase transition caused by the interlayer slip and structural strain is well suppressed under the synergistic effect of these two factors.As a result,NNMMT demonstrates exceptional capacity and cycling stability(reversible capacity of 109.8 mAh g^(-1) at 1 C and capacity retention of 97.35%after 100 cycles).Meanwhile,the higher proportion of the P2 phase enables NNMMT to maintain excellent rate capability(initial discharge capacity of 88.9 mAh g^(-1) at 5 C).Additionally,ex situ X-ray diffraction analyses before and after cycling demonstrated a significant suppression of the detrimental P2-O2 phase transition in NNMMT during the charge-discharge process,leading to a notable enhancement in structural stability.This work provides an innovative and efficient strategy for designing highly stable layered oxide cathodes.展开更多
文摘FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P] on experimental autoimmune encephalomyelitis (EAE) in rats and mice. Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4^+ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and (S)-FTY720-P. When FTY720 or (S)-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4^+ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4^+ T cells into the inflammation site. Cellular & Molecular Immunology. 2005;2(6):439-448.
文摘Background Methanesulfonic acid sodium salt (Dipyrone), an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle (V), methanesulfonic acid sodium salt (D), light damage model plus vehicle (MV) and light damage model plus methanesulfonic acid sodium salt (MD) groups (n=25 each). In the MD group, methanesulfonic acid sodium salt (100 mg/kg) was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy (TEM) were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I^m from the optic nerve. Electroretinography (ERG) test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c (CytC) and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group (P 〈0.05). TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 (Apaf-1), caspase 3, p53, p53-upregulated modulator of apoptosis (PUMA), Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.
文摘This paper introduces the new notion of ( p +0) summable operator. It is shown that this property is stable under small perturbation by selfadjoint operators.
基金supported in part by the A-STEP pro-gram of the Japan Science and Technology Agency(JST)(grant number JPMJTR23R6)a Grant-in-Aid for Scientific Research(KAKENHI)from the Japan Society for the Promotion of Science(JSPS)(grant number 23K13671).
文摘Carbon nanotubes(CNTs)are emerging as promising platforms for organic thermoelectric(TE)materials.However,the poor stability of n-doped states often presents a problem for the long-term operation of p-n junction TE modules.In this study,we synthesized a cross-linked organic superbase,2TBD-C10,as a dopant to create n-type CNTs that are resistant to air,heat,and humidity.When comparing the stability of 2TBD-C10-doped CNTs with those doped by a conventional superbase(TBD),we found that the enhanced stability could be attributed to the unique molecular structure of 2TBD-C10.This structure aids in effective adsorption on the CNT surfaces through multiple points,reduces volatility because of increased molecular weight,and suppresses water adsorption owing to the presence of hydrophobic alkyl chains.The results of our study demonstrate that tailoring the primary molecular structures of dopants can remarkably improve the stability of doped states in CNTs.The stable n-type materials were integrated into all-CNT TE modules,achieving good-to-excellent performance(power output of approximately 35μW from a temperature difference of approximately 65°C),making them suitable for powering wireless sensors and green light-emitting diodes.
基金supported by the National Natural Science Foundation of China(No.51971118,51771102 and 52371114).
文摘Transition metal chalcogenides(TMCs)are extensively employed as cathode materials for rechargeable aluminum batteries(RABs)due to their high theoretical specific capacity and voltage plateau.Although promising,practical applications are hindered by challenges such as inferior structural stability,slow reaction kinetics,and inadequate electronic conductivity.Herein,Mn-ion doping engineering and g-C_(3)N_(4) etched porous carbon frameworks(Mn-ZnSe@CNPC)were integrated to synergistically enhance the electrochemical properties of ZnSe.Through modulating the d-and p-band centers and regulating electronic interactions,Mn-ion doping enhances adsorption for solvent groups and reduces electron transfer energy barriers,resulting in Mn-ZnSe@CNPC cathodes with high redox activity and fast reaction kinetics.In addition,the porous carbon nanocages act as support frameworks,preventing the agglomeration of ZnSe nanoparticles and providing ample ion transport channels,thus addressing issues related to poor cyclability and slow electrochemical kinetics in RABs.Benefiting from the d–p orbital modulation strategy and structural advantages,the tailored Mn-ZnSe@CNPC cathode exhibits boosted electrochemical performance and excellent stability.
基金support from the National Natural Science Foundation of China(5237011751 and 52301282)the Key R&D program of Shanxi Province(202202070301016)the Shanxi Province Science Foundation for Youths(202303021212044 and 202303021212047).
文摘P2-type Na-NiMn oxides have garnered significant attention for sodium-ion batteries owing to their excellent rate capability.However,they are adversely affected by the harmful P2-O2 phase transitions,which cause substantial capacity degradation and poor cycling performance.In this work,a unique P2(84%)/O3(16%)biphasic layered oxide,Na_(0.76)Ni_(0.22)Mg_(0.11)Mn_(0.57)Ti_(0.1)O_(2)(NNMMT),is successfully designed and synthesized by a Mg/Ti co-doping strategy.The doping of Mg and Ti can form stable O-TM-O bonds,while the biphasic structure generates distinctive interlocked interfaces at the boundaries.The harmful phase transition caused by the interlayer slip and structural strain is well suppressed under the synergistic effect of these two factors.As a result,NNMMT demonstrates exceptional capacity and cycling stability(reversible capacity of 109.8 mAh g^(-1) at 1 C and capacity retention of 97.35%after 100 cycles).Meanwhile,the higher proportion of the P2 phase enables NNMMT to maintain excellent rate capability(initial discharge capacity of 88.9 mAh g^(-1) at 5 C).Additionally,ex situ X-ray diffraction analyses before and after cycling demonstrated a significant suppression of the detrimental P2-O2 phase transition in NNMMT during the charge-discharge process,leading to a notable enhancement in structural stability.This work provides an innovative and efficient strategy for designing highly stable layered oxide cathodes.