Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies...Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.展开更多
Src homology containing protein tyrosine phosphatase 2(SHP2)represents a noteworthy target for various diseases,serving as a well-known oncogenic phosphatase in cancers.As a result of the low cell permeability and poo...Src homology containing protein tyrosine phosphatase 2(SHP2)represents a noteworthy target for various diseases,serving as a well-known oncogenic phosphatase in cancers.As a result of the low cell permeability and poor bioavailability,the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy.Recently,a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified.In particular,few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors.This review summarizes the development and structureeactivity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies,with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity,higher oral bioavailability and better physicochemical properties.展开更多
Dear Editor,The loss of PINK1/Parkin-dependent mitochondrial clearance causes loss of dopaminergic neurons in the substantia nigra and contributes to the pathogenesis of Parkinson's disease(PD).Several kinases wer...Dear Editor,The loss of PINK1/Parkin-dependent mitochondrial clearance causes loss of dopaminergic neurons in the substantia nigra and contributes to the pathogenesis of Parkinson's disease(PD).Several kinases were reported to regulate the ubiquitin E3 ligase activity of Parkin through phosphorylation but the involvement of protein tyrosine phosphatase(PTPase)for Parkin activity remains elusive.展开更多
Nanoscale two-dimensional(2D)organic materials have attracted significant interest on account of their unique properties,which result from their ultrathin and flat morphology.Supramolecular 2D nanomaterials prepared b...Nanoscale two-dimensional(2D)organic materials have attracted significant interest on account of their unique properties,which result from their ultrathin and flat morphology.Supramolecular 2D nanomaterials prepared by bottom-up approaches have great potential in the creation of nanoscale devices with various applications,each controlled by the properties of its single-molecular components.Here,we report a uniform and controllable 2D rhombic micelles formed by block copolymers(BCPs)with poly(p-phenylenevinylene)(PPV)as core blocks.The supramolecular 2D nanostructures created in this way and driven byπ-πinteractions realize the precise separation of the semiconducting and insulating constituents of the constructed BCPs.With a vertical tunneling device design,the 2D rhombic micelles exhibited an on-off current ratio of>10^(4)and a high on-state current density of 6000 A cm^(−2)as the insulating layer was compressed by a conductive atomic force microscopy(C-AFM)probe.The tunneling device also shows a reproducible sensitivity on a flexible substrate,opening up potential flexible pressure sensor applications for such novel supramolecular 2D nanostructures.展开更多
基金supported by National Natural Science Foundation of China(Nos.81872877,81730100,91853109,82073975)School of Life Science(NJU)-Sipimo Joint Funds,Characteristic Innovation Project of Guangdong Provincial Education Department(Nos.2019GKTSCX039,2020KTSCX295,China),School-Level Scientific Research Project of Shenzhen Polytechnic(No.6021310023K,China)+1 种基金Natural Science Research of Jiangsu Higher Education Institutions of China(No.22KJB360005)Fundamental Research Funds for the Central Universities(No.020814380174,China).
文摘Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.
基金financial support by Guangdong Natural Science Funds for Distinguished Young Scholar(No.2018B030306017,China)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2018)+4 种基金National Natural Science Foundation of China(Nos.81602972,81673436 and 91853109,China)The Fundamental Research Funds for the Central Universities(20ykzd15,China)Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery(2019B030301005,China)Guangzhou Science and Technology Project(202002020082,China)Key-Area Research and Development Program of Guangdong Province(2020B1111110003,China)
文摘Src homology containing protein tyrosine phosphatase 2(SHP2)represents a noteworthy target for various diseases,serving as a well-known oncogenic phosphatase in cancers.As a result of the low cell permeability and poor bioavailability,the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy.Recently,a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified.In particular,few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors.This review summarizes the development and structureeactivity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies,with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity,higher oral bioavailability and better physicochemical properties.
基金This work was supported by the National Natural Science Foundation of China(Nos.91853109,81673436,81730100,81872877,81922067,81922064,81903620)Six Talents Peaks in Jiangsu Province(YY-004)Mountain-Climbing Talents Project of Nanjing University。
文摘Dear Editor,The loss of PINK1/Parkin-dependent mitochondrial clearance causes loss of dopaminergic neurons in the substantia nigra and contributes to the pathogenesis of Parkinson's disease(PD).Several kinases were reported to regulate the ubiquitin E3 ligase activity of Parkin through phosphorylation but the involvement of protein tyrosine phosphatase(PTPase)for Parkin activity remains elusive.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.52109111,52079004,and U20B2004)the Natural Science Foundation of Beijing(Grant No.3212023)the State Key Program for Basic Research of China(Grant No.MKS20210003).
基金This studywas supported financially by the National Natural Science Foundation of China(nos.21975115,21733005,and 11674150)the Shenzhen Fundamental Research Programs(nos.JCYJ20180302180238419,JCYJ20190809161413310,and KQJSCX20180319114442157)+4 种基金the Shenzhen Nobel Prize Scientists Laboratory Project(no.C17213101)the Guangdong Provincial Key Laboratory of Catalysis(no.2020B121201002)the Key-Area Research and Development Program of Guangdong Province(no.2019B010931001)the Guangdong Innovative and Entrepreneurial Research Team Program(under contract nos.2016ZT06G587 and 2016ZT06D348)the“Shenzhen Sci-Tech Fund”(no.KYTDPT20181011104007).
文摘Nanoscale two-dimensional(2D)organic materials have attracted significant interest on account of their unique properties,which result from their ultrathin and flat morphology.Supramolecular 2D nanomaterials prepared by bottom-up approaches have great potential in the creation of nanoscale devices with various applications,each controlled by the properties of its single-molecular components.Here,we report a uniform and controllable 2D rhombic micelles formed by block copolymers(BCPs)with poly(p-phenylenevinylene)(PPV)as core blocks.The supramolecular 2D nanostructures created in this way and driven byπ-πinteractions realize the precise separation of the semiconducting and insulating constituents of the constructed BCPs.With a vertical tunneling device design,the 2D rhombic micelles exhibited an on-off current ratio of>10^(4)and a high on-state current density of 6000 A cm^(−2)as the insulating layer was compressed by a conductive atomic force microscopy(C-AFM)probe.The tunneling device also shows a reproducible sensitivity on a flexible substrate,opening up potential flexible pressure sensor applications for such novel supramolecular 2D nanostructures.
