The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural...The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural products that are edible and safe for human use,are a good source of drug discovery with potential for uncovering novel applications,In this study,we tested 40 natural products of dietary supplements and identified capsaicin,a common dietary supplement abundant in chili peppers,as an inhibitor of Lassa virus(LASV)entry with EC5,of 6.9-10.0μmol/L using an HIV based pseudo virus platform.Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus(LCMV),showing a preferential activity against LASV.Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide(SSP)-GP2 transmembrane(GP2TM)region of the LASV surface glycoprotein.Mutational study revealed the key residues Ala25,Val431,Phe434 and Val435 in SsP-CP2TM region in capsaicin’s antiviral effect.This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV,providing detailed interaction hot spots in the unique SSP-GP2TMinterface of LASV glycoprotein that is crucial in fusion inhibition,and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.展开更多
A multi-channel fast super-resolution image reconstruction algorithm based on matrix observation model is proposed in the paper,which consists of three steps to avoid the computational complexity: a single image SR re...A multi-channel fast super-resolution image reconstruction algorithm based on matrix observation model is proposed in the paper,which consists of three steps to avoid the computational complexity: a single image SR reconstruction step,a registration step and a wavelet-based image fusion. This algorithm decomposes two large matrixes to the tensor product of two little matrixes and uses the natural isomorphism between matrix space and vector space to transform cost function based on matrix-vector products model to matrix form. Furthermore,we prove that the regularization part can be transformed to the matrix formed. The conjugate-gradient method is used to solve this new model. Finally,the wavelet fusion is used to integrate all the registered highresolution images obtained from the single image SR reconstruction step. The proposed algorithm reduces the storage requirement and the calculating complexity,and can be applied to large-dimension low-resolution images.展开更多
High fusion triple product has been obtained in the advanced scenarios with high normalized beta(βN)on the Experimental Advanced Superconducting Tokamak(EAST).A record value of ni0Ti0τE1.0×1019m^(-3)ke V s for ...High fusion triple product has been obtained in the advanced scenarios with high normalized beta(βN)on the Experimental Advanced Superconducting Tokamak(EAST).A record value of ni0Ti0τE1.0×1019m^(-3)ke V s for EAST deuterium plasma has been achieved,which is due to the formation of strong and broad internal transport barriers(ITBs)in ne,Teand Tiprofiles.Analysis shows that the strong ITB formation could be attributed to the reduction of transport from ITG modes.Based on the analysis,the physical mechanisms and methods to furtherimprove the plasma performance are discussed.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.81473256 and 81273561)the CAMS Innovation Fund for Medical Sciences(No.2016-I2M-1014,China)+3 种基金the Science and Technology Program of Beijing(No.Z151100000115008,China)the Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study(No.BZ0150,China)the Drug Innovation Major Project(Nos.2015ZX09102-023 and 2018ZX09711001-003-002,China)the Disciplines Construction Project(No.201920200802,China)
文摘The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural products that are edible and safe for human use,are a good source of drug discovery with potential for uncovering novel applications,In this study,we tested 40 natural products of dietary supplements and identified capsaicin,a common dietary supplement abundant in chili peppers,as an inhibitor of Lassa virus(LASV)entry with EC5,of 6.9-10.0μmol/L using an HIV based pseudo virus platform.Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus(LCMV),showing a preferential activity against LASV.Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide(SSP)-GP2 transmembrane(GP2TM)region of the LASV surface glycoprotein.Mutational study revealed the key residues Ala25,Val431,Phe434 and Val435 in SsP-CP2TM region in capsaicin’s antiviral effect.This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV,providing detailed interaction hot spots in the unique SSP-GP2TMinterface of LASV glycoprotein that is crucial in fusion inhibition,and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.
基金Sponsored by the National Natural Science Foundation of China(Grant No.60474016)the Fundamental Research Funds for the Central Universities(Grant No.HIT.NSRIF.2009046)
文摘A multi-channel fast super-resolution image reconstruction algorithm based on matrix observation model is proposed in the paper,which consists of three steps to avoid the computational complexity: a single image SR reconstruction step,a registration step and a wavelet-based image fusion. This algorithm decomposes two large matrixes to the tensor product of two little matrixes and uses the natural isomorphism between matrix space and vector space to transform cost function based on matrix-vector products model to matrix form. Furthermore,we prove that the regularization part can be transformed to the matrix formed. The conjugate-gradient method is used to solve this new model. Finally,the wavelet fusion is used to integrate all the registered highresolution images obtained from the single image SR reconstruction step. The proposed algorithm reduces the storage requirement and the calculating complexity,and can be applied to large-dimension low-resolution images.
基金supported by the National Key R&D Program of China(Nos.2017YFE0301205 and 2019YFE03040002)National Natural Science Foundation of China(Nos.11875289,11975271,11805136 and 12075284)。
文摘High fusion triple product has been obtained in the advanced scenarios with high normalized beta(βN)on the Experimental Advanced Superconducting Tokamak(EAST).A record value of ni0Ti0τE1.0×1019m^(-3)ke V s for EAST deuterium plasma has been achieved,which is due to the formation of strong and broad internal transport barriers(ITBs)in ne,Teand Tiprofiles.Analysis shows that the strong ITB formation could be attributed to the reduction of transport from ITG modes.Based on the analysis,the physical mechanisms and methods to furtherimprove the plasma performance are discussed.
