In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level ...In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation（OGD）/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages（E16 and E20）.The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate（NADPH） significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.展开更多
Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the imm...Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.展开更多
The sluggish kinetics of the oxygen evolution reaction(OER),an essential half-reaction of water splitting,lead to high OER overpotential and low energy-conversion efficiency,hampering its industrial application.Theref...The sluggish kinetics of the oxygen evolution reaction(OER),an essential half-reaction of water splitting,lead to high OER overpotential and low energy-conversion efficiency,hampering its industrial application.Therefore,considerable attention has been paid to the development of efficient catalysts to accelerate the OER.In this study,we synthesized the high-entropy oxides[(FeCoNiMnV)_(x)O]and used them as efficient OER catalysts.A simple oil-phase method was used to synthesize(FeCoNiMnV)_(x)O.The catalytic performances of the(FeCoNiMnV)_(x)O catalysts were modified by tuning the reaction temperature.The optimized(FeCoNiMnV)_(x)O catalyst exhibited multiple elemental interactions and abundant exposed active sites,leading to an overpotential of approximately 264 mV to reach a current density of 10 mA cm^(-2) in 1 M KOH and stability of 50 h at 1000 mA cm^(-2).Thus,a highly active OER catalyst was synthesized.This study provides an efficient approach for the synthesis of high-entropy oxides.展开更多
基金supported by the Natural Science Foundation of China (30930035 and 81271459)a "973" project from the Ministry of Science and Technology of China (2011CB51000)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD)the Graduate Education Innovation Project of Jiangsu Province (CXZZ12_0850)
文摘In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation（OGD）/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages（E16 and E20）.The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate（NADPH） significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.
文摘为探讨牡蛎肽(oyster peptide)的降糖作用及消化稳定性,以香港牡蛎(Grassostrea hongkongensis)为原料制备牡蛎肽,对其结构特征进行表征,通过体外降糖模型及模拟胃肠消化模型考察牡蛎肽的降糖活性及消化稳定性,并利用花色苷协同提高牡蛎肽消化稳定性和降糖活性。结果表明:牡蛎肽含有丰富的疏水性氨基酸,相对分子质量主要集中在1000之内;肽谱分析显示,牡蛎肽含有LYF、TLFLK、IRAGYD、TLHHRVH、ARNEANVNIY、CVIGR等15条肽段,具有显著的降糖肽结构特征;牡蛎肽对α-淀粉酶、α-葡萄糖苷酶和二肽基肽酶Ⅳ(DPP-Ⅳ)的半抑制浓度(IC50)分别为(3.66±0.47)、(8.62±0.66)、(2.60±0.46)mg/mL,具有良好的降糖活性;牡蛎肽的消化稳定性相对较差,经体外模拟胃肠消化后,其α-淀粉酶、α-葡萄糖苷酶和DPP-Ⅳ酶的抑制率显著下降了6.23%~32.48%(P<0.05);通过组合花色苷设计协同矩阵,选用Highest Single Agent(HSA)模型计算组合效果,结果显示,牡蛎肽和花色苷对α-葡萄糖苷酶(HSA协同得分3.503)、α-淀粉酶(HSA协同得分3.632)和DPP-Ⅳ(HSA协同得分3.156)具有协同抑制作用,经体外模拟胃肠消化试验验证,花色苷可以提高牡蛎肽的消化稳定性。研究表明,牡蛎肽具有降糖活性肽的特征结构,其与花色苷协同后具有显著的消化稳定性和降糖活性增效作用。
基金supported by the National Key Research and Development Program of China(No.2021YFA1201102)Henan Medical Science and Technology Joint Building Program(No.SBGJ202102132)+2 种基金Henan Province Youth Talent Promoting Project(No.2022HYTP047)the National Natural Science Foundation of China(Nos.82003255,82101385 and 82073231)Key Research and Development Project of Henan Province(No.232102311224)and First-Class Clinical Medicine Discipline Construction Talents Cultivation Project of Zhengzhou University.
文摘Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.
文摘The sluggish kinetics of the oxygen evolution reaction(OER),an essential half-reaction of water splitting,lead to high OER overpotential and low energy-conversion efficiency,hampering its industrial application.Therefore,considerable attention has been paid to the development of efficient catalysts to accelerate the OER.In this study,we synthesized the high-entropy oxides[(FeCoNiMnV)_(x)O]and used them as efficient OER catalysts.A simple oil-phase method was used to synthesize(FeCoNiMnV)_(x)O.The catalytic performances of the(FeCoNiMnV)_(x)O catalysts were modified by tuning the reaction temperature.The optimized(FeCoNiMnV)_(x)O catalyst exhibited multiple elemental interactions and abundant exposed active sites,leading to an overpotential of approximately 264 mV to reach a current density of 10 mA cm^(-2) in 1 M KOH and stability of 50 h at 1000 mA cm^(-2).Thus,a highly active OER catalyst was synthesized.This study provides an efficient approach for the synthesis of high-entropy oxides.
