[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total...[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining;the neuron and myelin sheath structure was observed by transmission electron microscopy;the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry;and the transfer of GRK2 was detected by western-blot.[Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dissolved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2.[Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI.展开更多
Isochronous mass spectrometry(IMS)of heavyion storage rings is a powerful tool for the mass measurements of short-lived nuclei.In IMS experiments,masses are determined through precision measurements of the revolution ...Isochronous mass spectrometry(IMS)of heavyion storage rings is a powerful tool for the mass measurements of short-lived nuclei.In IMS experiments,masses are determined through precision measurements of the revolution times of the ions stored in the ring.However,the revolution times cannot be resolved for particles with nearly the same mass-to-charge(m/q)ratios.To overcome this limitation and to extract the accurate revolution times for such pairs of ion species with very close m/q ratios,in our early work on particle identification,we analyzed the amplitudes of the timing signals from the detector based on the emission of secondary electrons.Here,the previous data analysis method is further improved by considering the signal amplitudes,detection efficiencies,and number of stored ions in the ring.A sensitive Z-dependent parameter is introduced in the data analysis,leading to a better resolution of ^(34)Ar^(18+) and ^(51)Co^(27+) with A/Z=17/9.The mean revolution times of ^(34)Ar^(18+) and ^(51)Co^(27+) are deduced,although their time difference is merely 1.8 ps.The uncorrected,overlapped peak of these ions has a full width at half maximum of 7.7 ps.The mass excess of ^(51)Co was determined to be-27;332e41T keV,which is in agreement with the previous value of-27;342e48T keV.展开更多
Preeclampsia(PE)is a serious pregnancy-related disorder characterized by dysregulated glycolysis and aberrant histone lactylation in the placenta.In this study,we developed folic acid(FA)-modified lipid nanoparticles(...Preeclampsia(PE)is a serious pregnancy-related disorder characterized by dysregulated glycolysis and aberrant histone lactylation in the placenta.In this study,we developed folic acid(FA)-modified lipid nanoparticles(FA-LNPs)encapsulating small interfering RNA targeting pyruvate kinase M(si-PKM),termed FA-LNP@si-PKM,to specifically modulate the molecular drivers of PE.Integrated transcriptomic and proteomic profiling identified PKM as a critical regulator in PE pathogenesis,associated with excessive lactate production and increased histone H3 lysine 18(H3K18)lactylation.Further mechanistic studies revealed that the histone acetyltransferase lysine acetyltransferase 7(KAT7)plays a pivotal role in mediating this lactylation process.In vitro silencing of PKM significantly reduced lactate accumulation,suppressed H3K18 lactylation,and attenuated pro-inflammatory cytokine production.Conversely,KAT7 overexpression abrogated these effects,highlighting its essential role in the PKM-lactate-H3K18la axis.In vivo,systemic administration of FA-LNP@si-PKM in an L-NAME-induced murine model of PE led to marked improvements,including reduced systolic blood pressure and proteinuria,diminished placental H3K18la levels,and lower expression of inflammatory markers IL-6 and TNF-α.These findings underscore the therapeutic potential of targeting the KAT7-H3K18la signaling axis using FA-LNP-mediated siRNA delivery.This nanotechnology-based approach offers a promising strategy for addressing the molecular etiology of PE and enhancing maternal and fetal outcomes.展开更多
A palladium-catalyzed tandem carbonylative lactonization and cycloaddition reaction of 2-vinyl acetophenones with alkenes and CO has been established.This reaction enables an efficient conversion of the easily availab...A palladium-catalyzed tandem carbonylative lactonization and cycloaddition reaction of 2-vinyl acetophenones with alkenes and CO has been established.This reaction enables an efficient conversion of the easily available alkenes to various bridged lactones through intermolecular cycloaddition.展开更多
基金Supported by Foundation of Anhui Academy of Medical Sciences(YKY2018006)
文摘[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining;the neuron and myelin sheath structure was observed by transmission electron microscopy;the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry;and the transfer of GRK2 was detected by western-blot.[Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dissolved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2.[Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI.
基金This work was supported by the National Key R&D Program of China(Nos.2016YFA0400504 and 2018YFA0404401)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB34000000)+4 种基金the National Natural Science Foundation of China(Nos.11905261,11805032,11975280,and 11605248)the CAS "Light of West China" Program,the China Postdoctoral Science Foundation(No.2019M660250)the FRIB-CSC Fellowship,China(No.201704910964)the International Postdoctoral Exchange Fellowship Program 2017 by the Office of China Postdoctoral Council(No.60 Document of OCPC,2017)the European Research Council(ERC)under the European Union’s Horizon 2020 Research and Innovation Programme(No.682841 "ASTRUm").
文摘Isochronous mass spectrometry(IMS)of heavyion storage rings is a powerful tool for the mass measurements of short-lived nuclei.In IMS experiments,masses are determined through precision measurements of the revolution times of the ions stored in the ring.However,the revolution times cannot be resolved for particles with nearly the same mass-to-charge(m/q)ratios.To overcome this limitation and to extract the accurate revolution times for such pairs of ion species with very close m/q ratios,in our early work on particle identification,we analyzed the amplitudes of the timing signals from the detector based on the emission of secondary electrons.Here,the previous data analysis method is further improved by considering the signal amplitudes,detection efficiencies,and number of stored ions in the ring.A sensitive Z-dependent parameter is introduced in the data analysis,leading to a better resolution of ^(34)Ar^(18+) and ^(51)Co^(27+) with A/Z=17/9.The mean revolution times of ^(34)Ar^(18+) and ^(51)Co^(27+) are deduced,although their time difference is merely 1.8 ps.The uncorrected,overlapped peak of these ions has a full width at half maximum of 7.7 ps.The mass excess of ^(51)Co was determined to be-27;332e41T keV,which is in agreement with the previous value of-27;342e48T keV.
基金supported by the 2025 National Health Commission Scientific Research Fund-Major Science and Technology Plan Project of Zhejiang Province(No.WKJ-ZJ-2533).
文摘Preeclampsia(PE)is a serious pregnancy-related disorder characterized by dysregulated glycolysis and aberrant histone lactylation in the placenta.In this study,we developed folic acid(FA)-modified lipid nanoparticles(FA-LNPs)encapsulating small interfering RNA targeting pyruvate kinase M(si-PKM),termed FA-LNP@si-PKM,to specifically modulate the molecular drivers of PE.Integrated transcriptomic and proteomic profiling identified PKM as a critical regulator in PE pathogenesis,associated with excessive lactate production and increased histone H3 lysine 18(H3K18)lactylation.Further mechanistic studies revealed that the histone acetyltransferase lysine acetyltransferase 7(KAT7)plays a pivotal role in mediating this lactylation process.In vitro silencing of PKM significantly reduced lactate accumulation,suppressed H3K18 lactylation,and attenuated pro-inflammatory cytokine production.Conversely,KAT7 overexpression abrogated these effects,highlighting its essential role in the PKM-lactate-H3K18la axis.In vivo,systemic administration of FA-LNP@si-PKM in an L-NAME-induced murine model of PE led to marked improvements,including reduced systolic blood pressure and proteinuria,diminished placental H3K18la levels,and lower expression of inflammatory markers IL-6 and TNF-α.These findings underscore the therapeutic potential of targeting the KAT7-H3K18la signaling axis using FA-LNP-mediated siRNA delivery.This nanotechnology-based approach offers a promising strategy for addressing the molecular etiology of PE and enhancing maternal and fetal outcomes.
基金We are grateful for the financial support from the National Natural Science Foundation of China(21790333 and 21925111)the Strategic Priority Research Program of the CAS(XDPB14).
文摘A palladium-catalyzed tandem carbonylative lactonization and cycloaddition reaction of 2-vinyl acetophenones with alkenes and CO has been established.This reaction enables an efficient conversion of the easily available alkenes to various bridged lactones through intermolecular cycloaddition.
