The main constituents of a typical medicinal herb, Polygonum multiflorum （Heshouwu in Chinese）, that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic do...The main constituents of a typical medicinal herb, Polygonum multiflorum （Heshouwu in Chinese）, that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide （LPS） and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent ＂knock-out＂ and ＂knock-in＂ strategy, we found that the ethyl acetate （EA） extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4＇-tetrahydroxy trans-stilbene-2-O-p-glucoside （trans-SG） and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization oftrans- SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.展开更多
The empirical valence bond model, solved by the DMRG technique, is applied to the systematical study of the photochemical processes of carotenoids. The polyenes with five up to one hundred of C== C bonds are investiga...The empirical valence bond model, solved by the DMRG technique, is applied to the systematical study of the photochemical processes of carotenoids. The polyenes with five up to one hundred of C== C bonds are investigated. The probability of the state arrangement for the conjugated bond, Pij, is evaluated. It is a parameter to correlate the bond lengths, and could also be applied to rationalizing the quantum yields of the photo-isomerization and the reaction constant of the quenching of singlet-oxygen happened to the external C== C bond of the carotenoids. The maximum reaction constant in long chain limit is determined as about 2.92×1010 L·mol-1·s-1.展开更多
Manufacturing machines converting energy to mechanical work at the molecular level is a vital pathway to ex- plore the microscopic world. A kind of operable molecular engines, composed offl-cyclodextrin （fl-CD）, ary...Manufacturing machines converting energy to mechanical work at the molecular level is a vital pathway to ex- plore the microscopic world. A kind of operable molecular engines, composed offl-cyclodextrin （fl-CD）, aryl, al- kene and amide moiety was investigated using molecular dynamics simulations combined with free-energy calcula- tions. To understand how the integrated alkene double bond controls the work performed on the engines, two alkene isomers of the prototype were considered as two molecular engines. The free-energy profiles delineating the binding process of the amide （Z）- and （E）-isomers for each alkene isomer with 1-adamantanol indicate that for the alkene （E）-isomer, the apparent work performed on the amide bond is 1.6 kcal/mol, while the alkene （Z）-isomer is incapa- ble to perform work. Direct switch on/off of engines caused by the isomerization of the alkene bond was, therefore, witnessed, in line with experimental measurements. Decomposition of the free-energy profile into different compo- nents and structural analyses suggest that the isomerization of the alkene bond controls the position of the aryl unit relative to the cavity of the CD, resulting in the difference among the free-energy profiles and the stark contrast of the work performed on engines.展开更多
PBOND is a web server that predicts the conformation of the peptide bond between any two amino acids. PBOND classifies the peptide bonds into one out of four classes, namely cis imide （cis-Pro）, cis amide （cis-non...PBOND is a web server that predicts the conformation of the peptide bond between any two amino acids. PBOND classifies the peptide bonds into one out of four classes, namely cis imide （cis-Pro）, cis amide （cis-nonPro）, trans imide （trans-Pro） and trans amide （trans-nonPro）. Moreover, for every prediction a reliability index is computed. The underlying structure of the server consists of three stages： （1） feature extraction, （2） feature selection and （3） peptide bond classification. PBOND can handle both single sequences as well as multiple sequences for batch processing. The predictions can either be directly downloaded from the web site or returned via e-mail. The PBOND web server is freely available at http：//195.251.198.21/pbond.html.展开更多
Photochromism of two bispyrryl-substituted ethenes, 2, 3-bis-(1-p-methoxyphenyl-5-phenyl-2-methyl-3-pyrryl)-2-butene (BPE1) and 2,3-bis(1-p-bromophenyl-4-phenyl-2-methyl-3-pyrryl)-2-butene (BPE2), was studied by laser...Photochromism of two bispyrryl-substituted ethenes, 2, 3-bis-(1-p-methoxyphenyl-5-phenyl-2-methyl-3-pyrryl)-2-butene (BPE1) and 2,3-bis(1-p-bromophenyl-4-phenyl-2-methyl-3-pyrryl)-2-butene (BPE2), was studied by laser flash photolysis technique. The results indicate that photocyclization of these compounds proceeds mainly via the excited triplet state, and the cis-trans isomerization proceeds mainly via the excited singlet state. After UV laser pulse irradiation, both photocylization and cis-trans isomerization of BPEl occur, but photocydization is the main reaction. On the other hand, laser photolysis of BPE2 leads mainly to photocydization. The effects of the substituents on the photochromic mechanism are also discussed.展开更多
文摘The main constituents of a typical medicinal herb, Polygonum multiflorum （Heshouwu in Chinese）, that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide （LPS） and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent ＂knock-out＂ and ＂knock-in＂ strategy, we found that the ethyl acetate （EA） extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4＇-tetrahydroxy trans-stilbene-2-O-p-glucoside （trans-SG） and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization oftrans- SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.
基金Part of the computational work was done on the SGI Origin 3800 and Dawning 3000 supercom-puters at Nanjing University. This work was supported by the National Natural Science Foundation of China (Grant Nos. 20073020 and 20273030).
文摘The empirical valence bond model, solved by the DMRG technique, is applied to the systematical study of the photochemical processes of carotenoids. The polyenes with five up to one hundred of C== C bonds are investigated. The probability of the state arrangement for the conjugated bond, Pij, is evaluated. It is a parameter to correlate the bond lengths, and could also be applied to rationalizing the quantum yields of the photo-isomerization and the reaction constant of the quenching of singlet-oxygen happened to the external C== C bond of the carotenoids. The maximum reaction constant in long chain limit is determined as about 2.92×1010 L·mol-1·s-1.
文摘Manufacturing machines converting energy to mechanical work at the molecular level is a vital pathway to ex- plore the microscopic world. A kind of operable molecular engines, composed offl-cyclodextrin （fl-CD）, aryl, al- kene and amide moiety was investigated using molecular dynamics simulations combined with free-energy calcula- tions. To understand how the integrated alkene double bond controls the work performed on the engines, two alkene isomers of the prototype were considered as two molecular engines. The free-energy profiles delineating the binding process of the amide （Z）- and （E）-isomers for each alkene isomer with 1-adamantanol indicate that for the alkene （E）-isomer, the apparent work performed on the amide bond is 1.6 kcal/mol, while the alkene （Z）-isomer is incapa- ble to perform work. Direct switch on/off of engines caused by the isomerization of the alkene bond was, therefore, witnessed, in line with experimental measurements. Decomposition of the free-energy profile into different compo- nents and structural analyses suggest that the isomerization of the alkene bond controls the position of the aryl unit relative to the cavity of the CD, resulting in the difference among the free-energy profiles and the stark contrast of the work performed on engines.
文摘PBOND is a web server that predicts the conformation of the peptide bond between any two amino acids. PBOND classifies the peptide bonds into one out of four classes, namely cis imide （cis-Pro）, cis amide （cis-nonPro）, trans imide （trans-Pro） and trans amide （trans-nonPro）. Moreover, for every prediction a reliability index is computed. The underlying structure of the server consists of three stages： （1） feature extraction, （2） feature selection and （3） peptide bond classification. PBOND can handle both single sequences as well as multiple sequences for batch processing. The predictions can either be directly downloaded from the web site or returned via e-mail. The PBOND web server is freely available at http：//195.251.198.21/pbond.html.
基金Project supported by the Chinese Academy of Sciencesthe National Natural Science Foundation of China
文摘Photochromism of two bispyrryl-substituted ethenes, 2, 3-bis-(1-p-methoxyphenyl-5-phenyl-2-methyl-3-pyrryl)-2-butene (BPE1) and 2,3-bis(1-p-bromophenyl-4-phenyl-2-methyl-3-pyrryl)-2-butene (BPE2), was studied by laser flash photolysis technique. The results indicate that photocyclization of these compounds proceeds mainly via the excited triplet state, and the cis-trans isomerization proceeds mainly via the excited singlet state. After UV laser pulse irradiation, both photocylization and cis-trans isomerization of BPEl occur, but photocydization is the main reaction. On the other hand, laser photolysis of BPE2 leads mainly to photocydization. The effects of the substituents on the photochromic mechanism are also discussed.
