Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol estrogens and a wide range of ...Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol estrogens and a wide range of endobiotics and xenobiotics that bear the catechol group.Currently,COMT inhibitors are used in combination with levodopa for the treatment of Parkinson’s disease in clinical practice.The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples,as well as for rapid screening and characterization of COMT inhibitors as drug candidates.This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications.Several lists of biochemical assays for measuring COMT activity,including the probe substrates,along with their analytical conditions and kinetic parameters,are presented.Finally,the challenges and future perspectives in the field,such as visualization of COMT activity in vivo and in situ,are highlighted.Collectively,this review article overviews the practical assays for measuring COMT activities in complex biological samples,which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.展开更多
Lower Cretaceous black shales in coastal southeastern China are of significance to the geological study of the Tethys and Pacific realms and to hydrocarbon exploration of southeastern China and East China Sea. However...Lower Cretaceous black shales in coastal southeastern China are of significance to the geological study of the Tethys and Pacific realms and to hydrocarbon exploration of southeastern China and East China Sea. However, the stratigraphic correlation, distribution patterns and hydrocarbon potential of the black shales have not been well constrained so far. In this study, the zircon UePb ages, organic petrologic and geochemical analyses were performed for representative outcrop sections in the region. Zircon UePb ages demonstrate that the Lower Cretaceous black shales in coastal southeastern China can be divided into two regional-scale sets. The first set was deposited during the early stage of the Early Cretaceous(K_1~1, BerriasianeHauterivian). The second set was deposited during the late stage of the Early Cretaceous(K_1~2), and might extend to the Taiwan Strait. Detailed organic geochemical analyses including organic matter abundance, type and maturity of the Lower Cretaceous black shales demonstrate that the organic matter abundance of the sources reached medium to good quality by the hydrocarbon source rock standards, and the average TOC values and the chloroform bitumen "A" of the K_1~1 black shales are higher. The type of organic matter is mainly type III, type II can also be found from the K_1~2 black shales. The thermal maturity of most samples is high to overmature. A relatively comprehensive hydrocarbon resource evaluation indicates that favorable regions are in the northern Guangdong Province for the K_1~1 and in the coastal region of Zhejiang Province and the westernFujian Province for the K_1~2. Sedimentology studies on the Shipu section for the K_1~1 black shales illuminated that the K_1~2 black shales in coastal southeastern China were mainly deposited during transgressive period. The relative sea level changes controlled the sequential development pattern of the K_1~2 black shales.展开更多
基金supported by the National Key Research and Development Program of China(2017YFC1700200,2017YFC1702000),the National Natural Science Foundation of China(81922070,81703604,81973286,81773687 and 81603187)Natural Science Foundation of Shanghai(18ZR1436500)+3 种基金Program of Shanghai Academic/Technology Research Leader(18XD1403600)Shuguang Program(18SG40)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commissionthe project sponsored by the development fund for Shanghai talents(2019)the Key Science and Technology Program of Shenyang supported by Shenyang Science and Technology Bureau(17-230-9-05).
文摘Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol estrogens and a wide range of endobiotics and xenobiotics that bear the catechol group.Currently,COMT inhibitors are used in combination with levodopa for the treatment of Parkinson’s disease in clinical practice.The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples,as well as for rapid screening and characterization of COMT inhibitors as drug candidates.This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications.Several lists of biochemical assays for measuring COMT activity,including the probe substrates,along with their analytical conditions and kinetic parameters,are presented.Finally,the challenges and future perspectives in the field,such as visualization of COMT activity in vivo and in situ,are highlighted.Collectively,this review article overviews the practical assays for measuring COMT activities in complex biological samples,which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.
基金funded by the National Natural Science Foundation of China (Grant No. 41472099)
文摘Lower Cretaceous black shales in coastal southeastern China are of significance to the geological study of the Tethys and Pacific realms and to hydrocarbon exploration of southeastern China and East China Sea. However, the stratigraphic correlation, distribution patterns and hydrocarbon potential of the black shales have not been well constrained so far. In this study, the zircon UePb ages, organic petrologic and geochemical analyses were performed for representative outcrop sections in the region. Zircon UePb ages demonstrate that the Lower Cretaceous black shales in coastal southeastern China can be divided into two regional-scale sets. The first set was deposited during the early stage of the Early Cretaceous(K_1~1, BerriasianeHauterivian). The second set was deposited during the late stage of the Early Cretaceous(K_1~2), and might extend to the Taiwan Strait. Detailed organic geochemical analyses including organic matter abundance, type and maturity of the Lower Cretaceous black shales demonstrate that the organic matter abundance of the sources reached medium to good quality by the hydrocarbon source rock standards, and the average TOC values and the chloroform bitumen "A" of the K_1~1 black shales are higher. The type of organic matter is mainly type III, type II can also be found from the K_1~2 black shales. The thermal maturity of most samples is high to overmature. A relatively comprehensive hydrocarbon resource evaluation indicates that favorable regions are in the northern Guangdong Province for the K_1~1 and in the coastal region of Zhejiang Province and the westernFujian Province for the K_1~2. Sedimentology studies on the Shipu section for the K_1~1 black shales illuminated that the K_1~2 black shales in coastal southeastern China were mainly deposited during transgressive period. The relative sea level changes controlled the sequential development pattern of the K_1~2 black shales.