Guan River Estuary and adjacent coastal area(GREC) suffer from serious pollution and eutrophicational problems over the recent years.Thus,reducing the land-based load through the national pollutant total load control ...Guan River Estuary and adjacent coastal area(GREC) suffer from serious pollution and eutrophicational problems over the recent years.Thus,reducing the land-based load through the national pollutant total load control program and developing hydrodynamic and water quality models that can simulate the complex circulation and water quality kinetics within the system,including longitudinal and lateral variations in nutrient and COD concentrations,is a matter of urgency.In this study,a three-dimensional,hydrodynamic,water quality model was developed in GREC,Northern Jiangsu Province.The complex three-dimensional hydrodynamics of GREC were modeled using the unstructured-grid,finite-volume,free-surface,primitive equation coastal ocean circulation model(FVCOM).The water quality model was adapted from the mesocosm nutrients dynamic model in the south Yellow Sea and considers eight compartments:dissolved inorganic nitrogen,soluble reactive phosphorus(SRP),phytoplankton,zooplankton,detritus,dissolved organic nitrogen(DON),dissolved organic phosphorus(DOP),and chemical oxygen demand.The hydrodynamic and water quality models were calibrated and confirmed for 2012 and 2013.A comparison of the model simulations with extensive dataset shows that the models accurately simulate the longitudinal distribution of the hydrodynamics and water quality.The model can be used for total load control management to improve water quality in this area.展开更多
Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its ...Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.展开更多
基金supported by Natural Science Foundation of China-Shandong Joint Fund for Marine Science Research Centers (Grant No.U1406403)the Sea Area Use Fund of Jiangsu Province (Environmental Capacity for the Key Coast of Jiangsu Province)+1 种基金the National Natural Science Foundation of China (No.41340046)Modeling work was completed at the Computing Services Center,Ocean University of China
文摘Guan River Estuary and adjacent coastal area(GREC) suffer from serious pollution and eutrophicational problems over the recent years.Thus,reducing the land-based load through the national pollutant total load control program and developing hydrodynamic and water quality models that can simulate the complex circulation and water quality kinetics within the system,including longitudinal and lateral variations in nutrient and COD concentrations,is a matter of urgency.In this study,a three-dimensional,hydrodynamic,water quality model was developed in GREC,Northern Jiangsu Province.The complex three-dimensional hydrodynamics of GREC were modeled using the unstructured-grid,finite-volume,free-surface,primitive equation coastal ocean circulation model(FVCOM).The water quality model was adapted from the mesocosm nutrients dynamic model in the south Yellow Sea and considers eight compartments:dissolved inorganic nitrogen,soluble reactive phosphorus(SRP),phytoplankton,zooplankton,detritus,dissolved organic nitrogen(DON),dissolved organic phosphorus(DOP),and chemical oxygen demand.The hydrodynamic and water quality models were calibrated and confirmed for 2012 and 2013.A comparison of the model simulations with extensive dataset shows that the models accurately simulate the longitudinal distribution of the hydrodynamics and water quality.The model can be used for total load control management to improve water quality in this area.
文摘Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.
