The rapid development and widespread use of ZnO nanoparticles(nZnO) in various industries have raised concerns about their potential environmental impact.Therefore,understanding the fate and role of nZnO in the natura...The rapid development and widespread use of ZnO nanoparticles(nZnO) in various industries have raised concerns about their potential environmental impact.Therefore,understanding the fate and role of nZnO in the natural environment is crucial for mitigating their hazardous effects on the environment and human safety.The purpose of the present study was to provide scientific support for understanding and eliminating the joint risk of nanoparticle and heavy metal pollution in the soil environment by revealing the co-transport characteristics of Cd(Ⅱ) and ZnO nanoparticles(nZnO) in soil under different ionic strength(IS) and pH.The impacts of different IS and pH on the co-transport of Cd(Ⅱ) and nZnO in a20 cm long with an inner diameter of 2.5 cm acrylic column packed with 10 cm high soil samples were investigated in the present study.In the above system,a500 μg L^(-1) Cd(Ⅱ) loaded nZnO suspension pulse with varying IS or pH was introduced into the soil column for leaching over 5 PVs,followed up by 5 PVs background solutions without nZnO.The IS was 1,10,or 50 mM NaCl,with pH6,or the pH was 6,7 or 8 with 1 mM NaCl.Meanwhile,Sedimentation experiments for nZnO,adsorption of Cd(Ⅱ) on soil,and nZnO,DLVO theory calculation for the same background condition were conducted.The presence of nZnO significantly increased the mobility of Cd(Ⅱ) as a result of its strong adsorption capacity for nZnO-associated Cd(Ⅱ).However,with the increase of IS,the co-transport of nZnO and Cd(Ⅱ) was decreased and the retention of nZnO in the soil column due to more nZnO attended to aggregate and sediment during the transport and the decrease in the adsorption capacity of nZnO for Cd(Ⅱ) by competition of Na^(+).When pH was 6,7,and 8,the co-transport of nZnO and Cd(Ⅱ) increased with higher pH due to the lower electrostatic attraction between nZnO and soil under higher pH.Meanwhile,the DLVO theory was fitted to describe the above co-transport process of nZnO and Cd(Ⅱ).More attention should be paid to the presence of nZnO on the migration of Cd(Ⅱ) in the natural soil to control the potential risk of nanoparticles and heavy metals to the environment.The risk of co-transport of nZnO and Cd(Ⅱ) might be controlled by adjusting IS and pH in the soil solution.展开更多
A novel alkalizing strain Enterobacter sp.LYX-2 that could resist 400 mg/L Cd was isolated from Cd-contaminated soil,which immobilized 96.05%Cd^(2+)from medium.Cd distribution analysis demonstrated that more than half...A novel alkalizing strain Enterobacter sp.LYX-2 that could resist 400 mg/L Cd was isolated from Cd-contaminated soil,which immobilized 96.05%Cd^(2+)from medium.Cd distribution analysis demonstrated that more than half of the Cd^(2+)was converted into extracellular precipitated Cd through mobilization of the alkali-producing mechanism by the strain LYX-2,achieving the high immobilization efficiency of Cd^(2+).Biosorption experiments revealed that strain LYX-2 had superior biosorption capacity of 48.28 mg/g for Cd.Pot experiments with Brassica rapa L.were performed with and without strain LYX-2.Compared to control,15.92%bioavailable Cd was converted to non-bioavailable Cd and Cd content in aboveground vegetables was decreased by 37.10%with addition of strain LYX-2.Available Cd was mainly immobilized through extracellular precipitation,cell-surface biosorption and intracellular accumulation of strain LYX-2,which was investigated through Cd distribution,Scanning Electron Microscope and Energy-Dispersive X-ray Spectroscopy(SEM-EDS),Fourier Transform Infrared Spectroscopy(FT-IR),X-ray Photoelectron Spectroscopy(XPS)and Transmission Electron Microscopy(TEM)analysis.In addition,the application of strain LYX-2 significantly promoted the growth of vegetables about 2.4-fold.Above results indicated that highly Cd-resistant alkalizing strain LYX-2,as a novel microbial passivator,had excellent ability and reuse value to achieve the remediation of Cd-contaminated soil coupled with safe production of vegetables simultaneously.展开更多
KRAS-PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here...KRAS-PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36 l(KD= 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36 l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft(PDX) models. It represents a promising lead compound for investigating the druggability of KRAS-PDEδ interaction.展开更多
基金supported by the National Key Research and Development Project of Chinathe National Natural Science Fund of China (Grant number 2018YFC1800403, 41571226)。
文摘The rapid development and widespread use of ZnO nanoparticles(nZnO) in various industries have raised concerns about their potential environmental impact.Therefore,understanding the fate and role of nZnO in the natural environment is crucial for mitigating their hazardous effects on the environment and human safety.The purpose of the present study was to provide scientific support for understanding and eliminating the joint risk of nanoparticle and heavy metal pollution in the soil environment by revealing the co-transport characteristics of Cd(Ⅱ) and ZnO nanoparticles(nZnO) in soil under different ionic strength(IS) and pH.The impacts of different IS and pH on the co-transport of Cd(Ⅱ) and nZnO in a20 cm long with an inner diameter of 2.5 cm acrylic column packed with 10 cm high soil samples were investigated in the present study.In the above system,a500 μg L^(-1) Cd(Ⅱ) loaded nZnO suspension pulse with varying IS or pH was introduced into the soil column for leaching over 5 PVs,followed up by 5 PVs background solutions without nZnO.The IS was 1,10,or 50 mM NaCl,with pH6,or the pH was 6,7 or 8 with 1 mM NaCl.Meanwhile,Sedimentation experiments for nZnO,adsorption of Cd(Ⅱ) on soil,and nZnO,DLVO theory calculation for the same background condition were conducted.The presence of nZnO significantly increased the mobility of Cd(Ⅱ) as a result of its strong adsorption capacity for nZnO-associated Cd(Ⅱ).However,with the increase of IS,the co-transport of nZnO and Cd(Ⅱ) was decreased and the retention of nZnO in the soil column due to more nZnO attended to aggregate and sediment during the transport and the decrease in the adsorption capacity of nZnO for Cd(Ⅱ) by competition of Na^(+).When pH was 6,7,and 8,the co-transport of nZnO and Cd(Ⅱ) increased with higher pH due to the lower electrostatic attraction between nZnO and soil under higher pH.Meanwhile,the DLVO theory was fitted to describe the above co-transport process of nZnO and Cd(Ⅱ).More attention should be paid to the presence of nZnO on the migration of Cd(Ⅱ) in the natural soil to control the potential risk of nanoparticles and heavy metals to the environment.The risk of co-transport of nZnO and Cd(Ⅱ) might be controlled by adjusting IS and pH in the soil solution.
基金supported by the National Key Research and Development Program of China (No.2018YFC1800403)the National Natural Science Foundation of China (No.41571226)the Scientific Research Fund of Zhejiang University (No.XY2021020)。
文摘A novel alkalizing strain Enterobacter sp.LYX-2 that could resist 400 mg/L Cd was isolated from Cd-contaminated soil,which immobilized 96.05%Cd^(2+)from medium.Cd distribution analysis demonstrated that more than half of the Cd^(2+)was converted into extracellular precipitated Cd through mobilization of the alkali-producing mechanism by the strain LYX-2,achieving the high immobilization efficiency of Cd^(2+).Biosorption experiments revealed that strain LYX-2 had superior biosorption capacity of 48.28 mg/g for Cd.Pot experiments with Brassica rapa L.were performed with and without strain LYX-2.Compared to control,15.92%bioavailable Cd was converted to non-bioavailable Cd and Cd content in aboveground vegetables was decreased by 37.10%with addition of strain LYX-2.Available Cd was mainly immobilized through extracellular precipitation,cell-surface biosorption and intracellular accumulation of strain LYX-2,which was investigated through Cd distribution,Scanning Electron Microscope and Energy-Dispersive X-ray Spectroscopy(SEM-EDS),Fourier Transform Infrared Spectroscopy(FT-IR),X-ray Photoelectron Spectroscopy(XPS)and Transmission Electron Microscopy(TEM)analysis.In addition,the application of strain LYX-2 significantly promoted the growth of vegetables about 2.4-fold.Above results indicated that highly Cd-resistant alkalizing strain LYX-2,as a novel microbial passivator,had excellent ability and reuse value to achieve the remediation of Cd-contaminated soil coupled with safe production of vegetables simultaneously.
基金supported by the National Key R&D Program of China(Grant No.2020YFA0509100)the National Natural Science Foundation of China(Grants 21738002,82030105,81725020 and 81903436)。
文摘KRAS-PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36 l(KD= 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36 l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft(PDX) models. It represents a promising lead compound for investigating the druggability of KRAS-PDEδ interaction.