20 Quantum chemical parameters of chlorophenol compounds were fully optimized by using B3LYP method on both 6-31G^＊ and 6-311G^＊ basis sets. These structural parameters are taken as theoretical descriptors, and the ...20 Quantum chemical parameters of chlorophenol compounds were fully optimized by using B3LYP method on both 6-31G^＊ and 6-311G^＊ basis sets. These structural parameters are taken as theoretical descriptors, and the experimental data of 20 compounds＇ aquatic photogen toxicity（-lgEC50） are used to perform stepwise regression in order to obtain two predicted -lgEC50 correlation models whose correlation coefficients R^2 are respectively 0.9186 and 0.9567. In addition, parameters of chlorine atom＇s substitutive positions and their correlations （NPCs） are taken as descriptors to obtain another predicted -lgEC50 model with the correlation coefficient R2 of 0.9444. Correlation degree of each independent variable in the three models is verified by using variance inflation factors （VIF） and t value. In the cross-validation method, cross-validation coefficients q^2 of 3 models are respectively 0.8748, 0.9119 and 0.8993, which indicates that the relativity and prediction ability of this model are superior to those of the model obtained by topological and BLYP methods.展开更多
Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some struct...Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some structural parameters. Consequently, Cl substitution positions were taken as theoretical descriptors to establish a novel QSPR model for predicting –lgSw of all PCB congeners. The model achieved in this work contains four variables, of which r^2 = 0.9527, q^2 = 0.9490 and SD = 0.25 with large t values. In addition, the variation inflation factors （VIFs） of variables in this model are all less than 5.0, suggesting high accuracy of the –lgSw predicting model. And the results of cross-validation test and method validation also show that the model exhibits optimum stability and better predictive capability than that from the AM1 method.展开更多
The structural and thermodynamic （PCTAs） in the ideal gas state at 298.15 K and 1.013 properties of 75 polychlorinated thianthrenes ×10^5 Pa have been calculated at the B3LYP/6- 31G＊ level using Gaussian 98 pr...The structural and thermodynamic （PCTAs） in the ideal gas state at 298.15 K and 1.013 properties of 75 polychlorinated thianthrenes ×10^5 Pa have been calculated at the B3LYP/6- 31G＊ level using Gaussian 98 program. Based on the output data of Gaussian, the isodesmic reactions were designed to calculate standard enthalpy of formation （△fH^θ） and standard free energy of formation （△fH^θ） of PCTAs congeners. The relations of these thermodynamic parameters with the number and position of C1 atom substitution （Npcs） were discussed, and it was found that there exists high correlation between thermodynamic parameters （total energy （TE）, zero-point vibrational energy （ZPE）, thermal correction to energy （Eth）, heat capacity at constant volume （Cv^θ）, entropy （S^θ）, enthalpy （H^θ）, free energy （G^θ）, standard enthalpies of formation （△fH^θ） and standard Gibbs energies of formation （△fG^θ）） and Npcs. On the basis of the relative magnitude of their △fG^θ, the order of relative stability of PCTA congeners was theoretically proposed. In addition, the correlations between structural parameters and Npcs were also discussed. The good correlations were found between molecular average polarizability （α）, energy of the highest occupied molecular orbital （EHOMO）, molecular volume （Vm） and Npcs, and all R^2 values are larger than 0.95. Moreover, it was supposed that the isomer groups with higher toxicity should be Tri-CTA and TCTA.展开更多
The thermodynamic properties of 135 polychlorinated phenothiazines （PCPTZs） in the standard state are calculated using a combination of quantum mechanical computations performed with the Gaussian 03 program at the B...The thermodynamic properties of 135 polychlorinated phenothiazines （PCPTZs） in the standard state are calculated using a combination of quantum mechanical computations performed with the Gaussian 03 program at the B3LYP/6-311G^＊＊ level, and their octanol-water partition coefficients （logKow） are calculated based on group contributions. The chlorine substitution pattern strongly influenced the thermodynamic properties and hydrophilicity of the compounds. The thermodynamic properties of congeners also depend on the chlorine substitution pattern. The effect of chlorine substitution pattern is quantitatively studied by considering the mmaber and position of Cl atom substitution （Npcs）. The results show that the Npcs model may be used to predict the thermodynamic properties and hydrophilicity for all 135 PCPTZ congeners.展开更多
A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and d...A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and diseases.Herein,we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells(NPCs)from human ESC/iPSCs on Type I Collagen.The derived cells not only displayed the requisite markers,but also behaved similarly to classic NPCs both in vitro and in vivo.Upon transplantation into traumatic brain injury model,the derived NPCs facilitated recovery from injury.We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen,and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day.Meanwhile,ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction.Totally,our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases’treatment.展开更多
There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is ...There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development（Betts,2010;US EPA,2015）.展开更多
Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells （NSC/NPCs） activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased different...Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells （NSC/NPCs） activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSClNPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive ＂big-data＂ processing, we report that NSCINPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSCINPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Inter- estingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The ErkJMapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSCINPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSCINPCs and their microenvironment in the context of the aging brain.展开更多
基金973 National Basic Research Program of China (2003CB415002)
文摘20 Quantum chemical parameters of chlorophenol compounds were fully optimized by using B3LYP method on both 6-31G^＊ and 6-311G^＊ basis sets. These structural parameters are taken as theoretical descriptors, and the experimental data of 20 compounds＇ aquatic photogen toxicity（-lgEC50） are used to perform stepwise regression in order to obtain two predicted -lgEC50 correlation models whose correlation coefficients R^2 are respectively 0.9186 and 0.9567. In addition, parameters of chlorine atom＇s substitutive positions and their correlations （NPCs） are taken as descriptors to obtain another predicted -lgEC50 model with the correlation coefficient R2 of 0.9444. Correlation degree of each independent variable in the three models is verified by using variance inflation factors （VIF） and t value. In the cross-validation method, cross-validation coefficients q^2 of 3 models are respectively 0.8748, 0.9119 and 0.8993, which indicates that the relativity and prediction ability of this model are superior to those of the model obtained by topological and BLYP methods.
基金This work was supported by the 973 National Basic Research Program of China (2003CB415002)the China Postdoctoral Science Foundation (No. 2003033486)
文摘Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some structural parameters. Consequently, Cl substitution positions were taken as theoretical descriptors to establish a novel QSPR model for predicting –lgSw of all PCB congeners. The model achieved in this work contains four variables, of which r^2 = 0.9527, q^2 = 0.9490 and SD = 0.25 with large t values. In addition, the variation inflation factors （VIFs） of variables in this model are all less than 5.0, suggesting high accuracy of the –lgSw predicting model. And the results of cross-validation test and method validation also show that the model exhibits optimum stability and better predictive capability than that from the AM1 method.
基金the National Natural Science Foundation of China(No.20737001 and 20477018)
文摘The structural and thermodynamic （PCTAs） in the ideal gas state at 298.15 K and 1.013 properties of 75 polychlorinated thianthrenes ×10^5 Pa have been calculated at the B3LYP/6- 31G＊ level using Gaussian 98 program. Based on the output data of Gaussian, the isodesmic reactions were designed to calculate standard enthalpy of formation （△fH^θ） and standard free energy of formation （△fH^θ） of PCTAs congeners. The relations of these thermodynamic parameters with the number and position of C1 atom substitution （Npcs） were discussed, and it was found that there exists high correlation between thermodynamic parameters （total energy （TE）, zero-point vibrational energy （ZPE）, thermal correction to energy （Eth）, heat capacity at constant volume （Cv^θ）, entropy （S^θ）, enthalpy （H^θ）, free energy （G^θ）, standard enthalpies of formation （△fH^θ） and standard Gibbs energies of formation （△fG^θ）） and Npcs. On the basis of the relative magnitude of their △fG^θ, the order of relative stability of PCTA congeners was theoretically proposed. In addition, the correlations between structural parameters and Npcs were also discussed. The good correlations were found between molecular average polarizability （α）, energy of the highest occupied molecular orbital （EHOMO）, molecular volume （Vm） and Npcs, and all R^2 values are larger than 0.95. Moreover, it was supposed that the isomer groups with higher toxicity should be Tri-CTA and TCTA.
文摘The thermodynamic properties of 135 polychlorinated phenothiazines （PCPTZs） in the standard state are calculated using a combination of quantum mechanical computations performed with the Gaussian 03 program at the B3LYP/6-311G^＊＊ level, and their octanol-water partition coefficients （logKow） are calculated based on group contributions. The chlorine substitution pattern strongly influenced the thermodynamic properties and hydrophilicity of the compounds. The thermodynamic properties of congeners also depend on the chlorine substitution pattern. The effect of chlorine substitution pattern is quantitatively studied by considering the mmaber and position of Cl atom substitution （Npcs）. The results show that the Npcs model may be used to predict the thermodynamic properties and hydrophilicity for all 135 PCPTZ congeners.
基金supported by the National Key Research and Development Program of China(2017YFA0104800)the“Strategic Priority Research Program”of the Chinese Academy of Sciences(XDA16010505)+5 种基金the National Natural Science Foundation of China(81570944,31300901,and 31900547)Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education FoundationScience and Technology Planning Project of Guangdong Province,China(2017B030314056)Natural Science Foundation of Guangdong Province,China(2017A030310098,2016A030313165,2015A030310026,and 2014A030313732)Science and Technology Planning Project of Guangzhou,China(201904010474)Shenzhen Peacock Plan(KQTD2016113015442590)。
文摘A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and diseases.Herein,we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells(NPCs)from human ESC/iPSCs on Type I Collagen.The derived cells not only displayed the requisite markers,but also behaved similarly to classic NPCs both in vitro and in vivo.Upon transplantation into traumatic brain injury model,the derived NPCs facilitated recovery from injury.We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen,and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day.Meanwhile,ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction.Totally,our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases’treatment.
基金the Canada Research Chairs Program,the Canadian Institutes of Health Research,and the Natural Sciences and Engineering Research Council of Canada for their support
文摘There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development（Betts,2010;US EPA,2015）.
基金This study was supported by China National Key Research and Development Program （2016YFA0100801 YS）, and the National Natural Science Foundation of China （Grant Nos. 8133030 YS and 31620103904 YS）, and grants： 2016YFC102705 YS 2014BAI04B07 WZL+1 种基金 81470715 YSTJ1504219036 WZL.
文摘Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells （NSC/NPCs） activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSClNPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive ＂big-data＂ processing, we report that NSCINPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSCINPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Inter- estingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The ErkJMapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSCINPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSCINPCs and their microenvironment in the context of the aging brain.
