Polychlorinated biphenyls(PCBs) can antagonize human pregnane X receptor(hPXR) activation.Such chemicals could pose a serious threat to the reproductive and developmental ability of humans.The quantitative structure a...Polychlorinated biphenyls(PCBs) can antagonize human pregnane X receptor(hPXR) activation.Such chemicals could pose a serious threat to the reproductive and developmental ability of humans.The quantitative structure activity relationship(QSAR) provides a promising method for the estimation of PCBs' antagonistic activity.In this investigation,a QSAR model was developed by using heuristic method and best subset modeling(r2 = 0.873,q2LOO=0.742).The built model was validated externally by splitting the original data set into training and prediction sets.The results of the model derived are as follows:r2 = 0.907,q2LOO=0.709,r2pred=0.676,suggesting developed QSAR model had good robustness and predictive ability.The applicability domain(AD) of the model was assessed by Williams plot.The antagonistic activity(?logKi) of 108 PCBs,which are unavailable by experiment at present,was predicted within the applicability domain of the model.The critical structural features related to the activity of PCBs were identified.展开更多
Understanding the factors influencing the distribution of plant species is crucial for enhancing the management of endangered ecosystems. This study investigated the response of Hedysarum criniferum Boiss, an endemic ...Understanding the factors influencing the distribution of plant species is crucial for enhancing the management of endangered ecosystems. This study investigated the response of Hedysarum criniferum Boiss, an endemic and endangered species to 25 environmental variables within its habitats with an area of 2.95×10^(5) km^(2) in arid and semi-arid rangelands of Iran. The purpose of this research is to identify the key environmental factors affecting the distribution and habitat preferences of H. criniferum for further conservation and restoration of the species. To predict the occurrence of H. criniferum and explore its relationship with environmental factors, we employed the best subset regression analysis, the hierarchical classification, and the extended Huisman-Olf-Fresco(eHOF) model. The results showed that four environmental variables, i.e., gravel content, pH, annual minimum temperature, and mean annual temperature showed significant correlations with the canopy cover of H. criniferum(P<0.05). The probability of H. criniferum occurrence increased with higher precipitation and elevation, while it decreased with higher mean annual temperature, annual minimum temperature, and gravel content. The species' response curves and their optimal values, as assessed by the eHOF model, indicated that the response to mean annual temperature, ranging from 12℃ to 16℃, was optimal at 13℃. The response to mean annual precipitation, within a range of 150–650 mm, was optimal at 650 mm. Elevation responses, spanning from 1546 to 2450 m, showed an optimum at 2450 m. Regarding soil characteristics, the response to gravel content, ranging from 13.0%–48.0%, demonstrated an optimal value at 20.0%. The pH levels, varying from 7.5 to 8.2, prompted a sine-shaped response with an optimal pH of 8.0. These findings provide valuable insights for predicting species occurrence and identifying suitable locations for restoration programs. Our study underscores the importance of considering multiple environmental variables in habitat suitability assessments. By incorporating these broader considerations, we can further refine predictive models and enhance conservation efforts aimed at restoring habitats conducive to the luxuriance of endangered species like H. criniferum.展开更多
The human pregnane X receptor（hPXR） plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiat...The human pregnane X receptor（hPXR） plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards h PXR. Heuristic method（HM）-Best Subset Modeling（BSM） and HM-Polynomial Neural Networks（PNN） were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain（AD） of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved（for HM-BSM, r^2=0.881, q^2_（LOO）=0.797, q^2_（EXT）=0.674; for HM-PNN, r^2=0.882, q^2_（LOO）=0.856, q^2_（EXT）=0.655）. The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to h PXR.展开更多
基金supported by the Science and Technology Development Foundation Key Project of Nanjing Medical University (09NJMUZ16)Natural Science Research Project of Institution of Higher Education of Jiangsu Province (11KJB180006)
文摘Polychlorinated biphenyls(PCBs) can antagonize human pregnane X receptor(hPXR) activation.Such chemicals could pose a serious threat to the reproductive and developmental ability of humans.The quantitative structure activity relationship(QSAR) provides a promising method for the estimation of PCBs' antagonistic activity.In this investigation,a QSAR model was developed by using heuristic method and best subset modeling(r2 = 0.873,q2LOO=0.742).The built model was validated externally by splitting the original data set into training and prediction sets.The results of the model derived are as follows:r2 = 0.907,q2LOO=0.709,r2pred=0.676,suggesting developed QSAR model had good robustness and predictive ability.The applicability domain(AD) of the model was assessed by Williams plot.The antagonistic activity(?logKi) of 108 PCBs,which are unavailable by experiment at present,was predicted within the applicability domain of the model.The critical structural features related to the activity of PCBs were identified.
基金funded by the Isfahan University of Technology,Iran.
文摘Understanding the factors influencing the distribution of plant species is crucial for enhancing the management of endangered ecosystems. This study investigated the response of Hedysarum criniferum Boiss, an endemic and endangered species to 25 environmental variables within its habitats with an area of 2.95×10^(5) km^(2) in arid and semi-arid rangelands of Iran. The purpose of this research is to identify the key environmental factors affecting the distribution and habitat preferences of H. criniferum for further conservation and restoration of the species. To predict the occurrence of H. criniferum and explore its relationship with environmental factors, we employed the best subset regression analysis, the hierarchical classification, and the extended Huisman-Olf-Fresco(eHOF) model. The results showed that four environmental variables, i.e., gravel content, pH, annual minimum temperature, and mean annual temperature showed significant correlations with the canopy cover of H. criniferum(P<0.05). The probability of H. criniferum occurrence increased with higher precipitation and elevation, while it decreased with higher mean annual temperature, annual minimum temperature, and gravel content. The species' response curves and their optimal values, as assessed by the eHOF model, indicated that the response to mean annual temperature, ranging from 12℃ to 16℃, was optimal at 13℃. The response to mean annual precipitation, within a range of 150–650 mm, was optimal at 650 mm. Elevation responses, spanning from 1546 to 2450 m, showed an optimum at 2450 m. Regarding soil characteristics, the response to gravel content, ranging from 13.0%–48.0%, demonstrated an optimal value at 20.0%. The pH levels, varying from 7.5 to 8.2, prompted a sine-shaped response with an optimal pH of 8.0. These findings provide valuable insights for predicting species occurrence and identifying suitable locations for restoration programs. Our study underscores the importance of considering multiple environmental variables in habitat suitability assessments. By incorporating these broader considerations, we can further refine predictive models and enhance conservation efforts aimed at restoring habitats conducive to the luxuriance of endangered species like H. criniferum.
基金supported by grants from the Natural Science Research Project of Institution of Higher Education of Jiangsu Province(No.11KJB180006)National Natural Science Foundation of China(No.21277074 and No.81302458)
文摘The human pregnane X receptor（hPXR） plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards h PXR. Heuristic method（HM）-Best Subset Modeling（BSM） and HM-Polynomial Neural Networks（PNN） were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain（AD） of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved（for HM-BSM, r^2=0.881, q^2_（LOO）=0.797, q^2_（EXT）=0.674; for HM-PNN, r^2=0.882, q^2_（LOO）=0.856, q^2_（EXT）=0.655）. The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to h PXR.
