Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a vari...Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a variety of different biolog-ical activities,which cannot be adopted by the unassembled protein alone.Thus,it is important to investigate the molecular basis of self-assembly of protein amyloid aggregates and how the aggregated protein structure determines its function.In the review,wefirstly introduce our structural knowledge on how different amyloid pro-teins undergo conformational transition and assemble into amyloid aggregate,with the main focus on amyloidfibril,which is the major species of amyloid aggregate.Then,we elaborate how different structures of amyloidfibrils enable them to fulfill highly diverse functions in either physiological or pathological condition.Further-more,we discuss the structural polymorph which is a very unique feature of amyloidfibril,and its implication in understanding the structure-function relationship of amy-loidfibrils.Finally,we point out the importance of applying and integrating new approaches for deepening the structure-function study of amyloidfibrils and high-light the potential of designing amyloidfibril-based functional bio-nanomaterials for application.展开更多
Spirolindemers A and B,unprecedented lindenane sesquiterpenoid dimer(1)and trimer(2)equipped with oxaspiro[4.5]decane unit,were discovered from the medicinal plant Chloranthus henryi.Their structures including absolut...Spirolindemers A and B,unprecedented lindenane sesquiterpenoid dimer(1)and trimer(2)equipped with oxaspiro[4.5]decane unit,were discovered from the medicinal plant Chloranthus henryi.Their structures including absolute configurations were achieved by HRMS,NMR,ECD,X-ray diffraction analyses,and quantum chemical calculations.Biogenetically,hetero-and homo-Diels-Alder additions may dominate the formation of oxaspiro[4.5]decane and spiro[4.5]decane skeletons,respectively.Compound 1 showed anti-inflammatory activity by inhibiting the expression of iNOS and COX-2.展开更多
Elodexanthones A—J (1—10), two pairs of rearranged isoprenylated xanthone enantiomers with an unprecedent 6/6/5/6 tetracyclic core (1—2) along with seven new isoprenylated xanthones (3—9) and a pair of phenylpropa...Elodexanthones A—J (1—10), two pairs of rearranged isoprenylated xanthone enantiomers with an unprecedent 6/6/5/6 tetracyclic core (1—2) along with seven new isoprenylated xanthones (3—9) and a pair of phenylpropanoid xanthones (10), were purified and enantio-separated from the whole plant of Hypericum elodeoides. Their structures including absolute configurations were characterized by the comprehensive analysis of NMR, HRESIMS, NMR calculations, and ECD calculations. Through Bayer-Villiger oxidation, Claisen condensation and electrophilic addition, the rearranged skeletons of elodexanthones A—B (1—2) were generated from isoprenylated xanthone precursors. The bioactivities evaluation exhibited that compounds 3, 5, 8—10 showed anti-inflammatory activity with the IC_(50) values in the range of 9.53—34.39 μmol/L, and compounds 3—7, and 9 showed notable α-glucosidase inhibitory activity (IC_(50): 6.02—257.11 μmol/L).展开更多
Twenty-two new limonoids,mufolinoids A—V(1—22),including six rings A,B-seco limonoids(1—6),twelve ring A-seco limonoids(7—18),four ring-intact limonoids(19—22),together with thirteen known compounds(23—35)were i...Twenty-two new limonoids,mufolinoids A—V(1—22),including six rings A,B-seco limonoids(1—6),twelve ring A-seco limonoids(7—18),four ring-intact limonoids(19—22),together with thirteen known compounds(23—35)were isolated from Munronia unifoliolata.Their structures including absolute configurations were elucidated by combination of NMR,HR-MS,single-crystal X-ray diffraction and calculations of ECD and NMR technologies.Compounds 24,25,33,34 could be significantly reversed the multidrug resistance of MCF-7/doxorubicin(DOX)cells,and the reversal fold(RF)was much higher than that of positive drug Verapamil.Compounds 24,28,and 29 exhibited significant anti-inflammatory activity with the IC50 values in the range of 17.7—39.4μmol/L.Furthermore,compound 29 could markedly inhibit the release of IL-1βby inhibiting the initiation and assembly of NLRP3 inflammasome,which demonstrates the great potential of limonoids as an anti-inflammatory agent.展开更多
The nucleocapsid(N)protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation,which enables its incorporation into stress granules(SGs)of host cells.However,whether SG invasion by...The nucleocapsid(N)protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation,which enables its incorporation into stress granules(SGs)of host cells.However,whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow,neither do we know its con-sequence.Here,we used SARS-CoV-2 to infect mam-malian cells and observed the incorporation of N protein into SGs,which resulted in markedly impaired self-dis-assembly but stimulated cell cellular clearance of SGs.NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific tran-sient interactions,which not only expedites the phase transition of these proteins to aberrant amyloid aggre-gation in vitro,but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells.In addition,we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells.Our work indicates that SARS-CoV-2 infection can impair the dis-assembly of host SGs and promote the aggregation of SG-related amyloid proteins,which may lead to an increased risk of neurodegeneration.展开更多
Mufolinin A(1),a ring A-seco rearranged limonoid with an unprecedented ethyl at C-10 and novel 6/6/6/5 fused-ring skeleton,together with three new potential precursors(ring A-seco limonoids,2–4)were isolated from Mun...Mufolinin A(1),a ring A-seco rearranged limonoid with an unprecedented ethyl at C-10 and novel 6/6/6/5 fused-ring skeleton,together with three new potential precursors(ring A-seco limonoids,2–4)were isolated from Munronia unifoliolata.Their structures and absolute configurations were confirmed by nuclear magnetic resonance(NMR),high resolution electrospray ionization mass spectroscopy(HRESIMS),X-ray crystallography,electronic circular dichroism(ECD)calculations and NMR calculations with DP4+analyses.The unprecedented ethyl group of 1 was hypothesized to be derived from methyl migration and ring reduction rearrangement of ring A-seco limonoid 4.Compounds 2 and 4 showed significant multidrug resistance(MDR)reversal activities in MCF-7/DOX cells with reversal fold(RF)values of 13.1 and 8.0,respectively.展开更多
Since 2002,the People's Bank of China has frequently used both quantity-based direct monetary instruments and price-based indirect monetary instruments to promote economic growth and stabilize price level.Specific...Since 2002,the People's Bank of China has frequently used both quantity-based direct monetary instruments and price-based indirect monetary instruments to promote economic growth and stabilize price level.Specifically,this study estimates 13 three-variable factor-augmented vector autoregression (FAVAR) models to explore how two types of monetary instruments affect China's economy and price level.Overall,we find that monetary policy has positive effects on China's economy and price level.Second,this study clearly states that the effectiveness of China's monetary policy on the economy has depended on China's quantity-based direct monetary instruments since 2002.Third,the effectiveness of quantity-based direct monetary instruments on China's economy and price level is dependent on the significant and positive effects of quantity-based direct monetary instruments after the 2008 financial crisis.Fourth,the significant and positive effects of price-based indirect monetary instruments on China's economy and price level before 2008 cannot fundamentally change their current insignificant effects on China's economy and price level.展开更多
基金National Natural Science Foundation(NSF)of China,Grant/Award Numbers:82188101,32171236,31872716,32170683the Science and Technology Commission of Shanghai Municipality(STCSM),Grant/Award Numbers:20XD1425000,2019SHZDZX02the Shanghai Pilot Program for Basic Research–Chinese Academy of Science,Shanghai Branch,Grant/Award Number:CYJ-SHFY-2022-005。
文摘Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a variety of different biolog-ical activities,which cannot be adopted by the unassembled protein alone.Thus,it is important to investigate the molecular basis of self-assembly of protein amyloid aggregates and how the aggregated protein structure determines its function.In the review,wefirstly introduce our structural knowledge on how different amyloid pro-teins undergo conformational transition and assemble into amyloid aggregate,with the main focus on amyloidfibril,which is the major species of amyloid aggregate.Then,we elaborate how different structures of amyloidfibrils enable them to fulfill highly diverse functions in either physiological or pathological condition.Further-more,we discuss the structural polymorph which is a very unique feature of amyloidfibril,and its implication in understanding the structure-function relationship of amy-loidfibrils.Finally,we point out the importance of applying and integrating new approaches for deepening the structure-function study of amyloidfibrils and high-light the potential of designing amyloidfibril-based functional bio-nanomaterials for application.
基金The authors acknowledge supports from the National Natural Science Foundation of China(No.32070389)the"Double First-Class"University project(CPU2018GY08).
文摘Spirolindemers A and B,unprecedented lindenane sesquiterpenoid dimer(1)and trimer(2)equipped with oxaspiro[4.5]decane unit,were discovered from the medicinal plant Chloranthus henryi.Their structures including absolute configurations were achieved by HRMS,NMR,ECD,X-ray diffraction analyses,and quantum chemical calculations.Biogenetically,hetero-and homo-Diels-Alder additions may dominate the formation of oxaspiro[4.5]decane and spiro[4.5]decane skeletons,respectively.Compound 1 showed anti-inflammatory activity by inhibiting the expression of iNOS and COX-2.
基金supported by the National Natural Science Foundation of China(32170406)the“Double First-Class”University project(CPU2018GY08).
文摘Elodexanthones A—J (1—10), two pairs of rearranged isoprenylated xanthone enantiomers with an unprecedent 6/6/5/6 tetracyclic core (1—2) along with seven new isoprenylated xanthones (3—9) and a pair of phenylpropanoid xanthones (10), were purified and enantio-separated from the whole plant of Hypericum elodeoides. Their structures including absolute configurations were characterized by the comprehensive analysis of NMR, HRESIMS, NMR calculations, and ECD calculations. Through Bayer-Villiger oxidation, Claisen condensation and electrophilic addition, the rearranged skeletons of elodexanthones A—B (1—2) were generated from isoprenylated xanthone precursors. The bioactivities evaluation exhibited that compounds 3, 5, 8—10 showed anti-inflammatory activity with the IC_(50) values in the range of 9.53—34.39 μmol/L, and compounds 3—7, and 9 showed notable α-glucosidase inhibitory activity (IC_(50): 6.02—257.11 μmol/L).
基金sponsored by the National Natural Science Foundation of China(31470416)the 111 Project from Ministry of Education of Chinathe State Administration of Foreign Export Affairs of China(B18056).
文摘Twenty-two new limonoids,mufolinoids A—V(1—22),including six rings A,B-seco limonoids(1—6),twelve ring A-seco limonoids(7—18),four ring-intact limonoids(19—22),together with thirteen known compounds(23—35)were isolated from Munronia unifoliolata.Their structures including absolute configurations were elucidated by combination of NMR,HR-MS,single-crystal X-ray diffraction and calculations of ECD and NMR technologies.Compounds 24,25,33,34 could be significantly reversed the multidrug resistance of MCF-7/doxorubicin(DOX)cells,and the reversal fold(RF)was much higher than that of positive drug Verapamil.Compounds 24,28,and 29 exhibited significant anti-inflammatory activity with the IC50 values in the range of 17.7—39.4μmol/L.Furthermore,compound 29 could markedly inhibit the release of IL-1βby inhibiting the initiation and assembly of NLRP3 inflammasome,which demonstrates the great potential of limonoids as an anti-inflammatory agent.
基金This work was supported by the National Natural Science Foundation(NSF)of China(32170683,82188101,32171236,31872716,32070049,82041016)the Major State Basic Research Development Program(2019YFE0120600)+5 种基金the Science and Technology Commission of Shanghai Municipality(STCSM)(20XD1425000 and 2019SHZDZX02)CAS project for Young Scientists in Basic research(YSBR-009)the Eastem Scholar project supported by Shanghai Municipal Education Commission,National Key R&D Program of China(2021YFC2301700,2021YFA1301900)Yunnan Key Research and Development project(202103AQ100001)CAMS Innovation Fund for Medical Sciences(2021-12M-1-038)special research fund on COVID-19 of Sichuan Province(2020YFS0010).
文摘The nucleocapsid(N)protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation,which enables its incorporation into stress granules(SGs)of host cells.However,whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow,neither do we know its con-sequence.Here,we used SARS-CoV-2 to infect mam-malian cells and observed the incorporation of N protein into SGs,which resulted in markedly impaired self-dis-assembly but stimulated cell cellular clearance of SGs.NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific tran-sient interactions,which not only expedites the phase transition of these proteins to aberrant amyloid aggre-gation in vitro,but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells.In addition,we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells.Our work indicates that SARS-CoV-2 infection can impair the dis-assembly of host SGs and promote the aggregation of SG-related amyloid proteins,which may lead to an increased risk of neurodegeneration.
基金supported by the National Natural Science Foundation of China(No.31470416)the 111 Project from Ministry of Education of China and the State Administration of Foreign Export Affairs of China(No.B18056).ll supported in part by SciGrid,Chinese Academy of Sciences。
文摘Mufolinin A(1),a ring A-seco rearranged limonoid with an unprecedented ethyl at C-10 and novel 6/6/6/5 fused-ring skeleton,together with three new potential precursors(ring A-seco limonoids,2–4)were isolated from Munronia unifoliolata.Their structures and absolute configurations were confirmed by nuclear magnetic resonance(NMR),high resolution electrospray ionization mass spectroscopy(HRESIMS),X-ray crystallography,electronic circular dichroism(ECD)calculations and NMR calculations with DP4+analyses.The unprecedented ethyl group of 1 was hypothesized to be derived from methyl migration and ring reduction rearrangement of ring A-seco limonoid 4.Compounds 2 and 4 showed significant multidrug resistance(MDR)reversal activities in MCF-7/DOX cells with reversal fold(RF)values of 13.1 and 8.0,respectively.
基金The anthors thank the support from Tianjin Philosophy and Social Science Planning Project(No.TJYYQN19-004)Project of National and Regional Research Center,Ministry of Education(No.ZX20170183)National Natural Science Foundation Youth Project(No.71803089).
文摘Since 2002,the People's Bank of China has frequently used both quantity-based direct monetary instruments and price-based indirect monetary instruments to promote economic growth and stabilize price level.Specifically,this study estimates 13 three-variable factor-augmented vector autoregression (FAVAR) models to explore how two types of monetary instruments affect China's economy and price level.Overall,we find that monetary policy has positive effects on China's economy and price level.Second,this study clearly states that the effectiveness of China's monetary policy on the economy has depended on China's quantity-based direct monetary instruments since 2002.Third,the effectiveness of quantity-based direct monetary instruments on China's economy and price level is dependent on the significant and positive effects of quantity-based direct monetary instruments after the 2008 financial crisis.Fourth,the significant and positive effects of price-based indirect monetary instruments on China's economy and price level before 2008 cannot fundamentally change their current insignificant effects on China's economy and price level.