The co-occurrence of glyphosate(GLP)and aminomethylphosphonic acid(AMPA)in contaminated water,soil,sediment and plants is a cause for concern due to potential threats to the ecosystem and human health.A major route of...The co-occurrence of glyphosate(GLP)and aminomethylphosphonic acid(AMPA)in contaminated water,soil,sediment and plants is a cause for concern due to potential threats to the ecosystem and human health.A major route of exposure is through contact with contaminated soil and consumption of crops containing GLP and AMPA residues.However,clay-based sorption strategies for mixtures of GLP and AMPA in soil,plants and garden produce have been very limited.In this study,in vitro soil and in vivo genetically modified corn models were used to establish the proof of concept that the inclusion of clay sorbents in contaminated soils will reduce the bioavailability of GLP and AMPA in soils and their adverse effects on plant growth.Effects of chemical concentration(1–10 mg/kg),sorbent dose(0.5%-3%in soil and 0.5%-1%in plants)and duration(up to 28 days)on sorption kinetics were studied.The time course results showed a continuous GLP degradation to AMPA.The inclusion of calcium montmorillonite(CM)and acid processed montmorillonite(APM)clays at all doses significantly and consistently reduced the bioavailability of both chemicals from soils to plant roots and leaves in a dose-and time-dependent manner without detectable dissociation.Plants treated with 0.5%and 1%APM inclusion showed the highest growth rate(p≤0.05)and lowest chemical bioavailability with up to 76%reduction in roots and57%reduction in leaves.Results indicated that montmorillonite clays could be added as soil supplements to reduce hazardous mixtures of GLP and AMPA in soils and plants.展开更多
The aim of this study is to evaluate the hydrogeochemical characteristics and water environmental quality of shallow groundwater in the Suxian mining area of Huaibei coalfield,China.The natural formation process of sh...The aim of this study is to evaluate the hydrogeochemical characteristics and water environmental quality of shallow groundwater in the Suxian mining area of Huaibei coalfield,China.The natural formation process of shallow groundwater in Suxian is explored using Piper trilinear charts and Gibbs diagrams,and by examining the ratios between the major ions.United States Salinity Laboratory(USSL)charts,Wilcox diagrams,and the water quality index(WQI)are further employed to quantify the differences in water quality.The results reveal that the main hydrochemical facies of groundwater are HC03-Ca,and that silicate dissolution is the main factor controlling the ion content in shallow groundwater.The USSL charts and Wilcox diagrams show that most of the water samples would be acceptable for use in irrigation systems.The WQI results for each water sample are compared and analyzed,and the quality of groundwater samples around collapse ponds is found to be relatively poor.展开更多
The cycloaddition of CO2 with epoxides catalyzed by ionic liquids(ILs)has been a widely ongoing studied hot topic over the years.Recent experimental research has shown that the protic ionic liquids(PILs)behave stronge...The cycloaddition of CO2 with epoxides catalyzed by ionic liquids(ILs)has been a widely ongoing studied hot topic over the years.Recent experimental research has shown that the protic ionic liquids(PILs)behave stronger hydrogen proton donating ability than aprotic ionic liquids(APILs),and can effectively catalyze the cycloaddition of CO2.Unfortunately,the mechanistic explanation remains primarily unraveled.Herein,a detailed simulation study on the cycloaddition reaction catalyzed by PIL([HDBU][Mim])in comparison with APIL([MeDBU][Mim])re-action catalysts was conducted,including the three-step route(ring-opening of PO(propylene oxide),insertion of CO2 and ring-closure of propylene carbonate(PC))and two-step route(simultaneously ring-opening of PO and addition of CO2,and then ring-closure of PC).Based on the activation energy barrier of the rate-determining step,PIL preferentially activates PO as the optimal route for the reaction with the energy barrier of 23.2 kcal mol-1,while that of APIL is 31.2 kcal mol-1.The role of[HDBU]+in the reaction was also explored and found that the direct formation of intermolecular hydrogen bond(H-bond)between[HDBU]+and the reactants(PO+CO2)was unfavorable for the reaction,while the cooperation with the anion[Mim]-to assist indirectly was more conducive.To fully consider the reaction microenvironment of ILs,ONIOM calculation was used to study the solvent effect.At last,the above conclusions were further verified by the analysis of intermediates with charge,non-covalent interaction(NCI),and atoms in molecules(AIM)methods.The computational findings show that ILs studied in this work have dual functions of catalyst and solvent,enabling a microscopic understanding of the ILs catalyst for CO2 utilization as well as providing guidance for the rational design of more efficient ILs-based catalysts.展开更多
The widespread use of pesticides has resulted in detectable residues throughout the environment,sometimes at concentrations well above regulatory limits.Therefore,the development of safe,effective,field-practical,and ...The widespread use of pesticides has resulted in detectable residues throughout the environment,sometimes at concentrations well above regulatory limits.Therefore,the development of safe,effective,field-practical,and economically feasible strategies to mitigate the effects of pesticides is warranted.Glyphosate is an organophosphorus herbicide that is degraded to aminomethylphosphonic acid(AMPA),a toxic and persistent metabolite that can accumulate in soil and sediment and translocate to plants.In this study,we investigated the binding efficacy of activated carbon(AC)and calcium montmorillonite(CM)clay to decrease AMPA bioavailability from soil and AMPA translocation to plants.Adsorption isotherms and thermodynamic studies on AC and CM were conducted and showed tight binding(enthalpy values>-20 k J/mol)for AMPA with high capacities(0.25 mol/kg and 0.38 mol/kg,respectively),based on derivations from the Langmuir model.A hydra assay was utilized to indicate toxicity of AMPA and the inclusion of 1%AC and CM both resulted in 90%protection of the hydra(**p≤0.01).Further studies in glyphosate-contaminated soil showed that AC and CM significantly reduced AMPA bioavailability by 53%and 44%,respectively.Results in genetically modified(GM)corn showed a conversion of glyphosate to AMPA in roots and sprouts over a 10-day exposure duration.Inclusion of AC and CM reduced AMPA residues in roots and sprouts by 47%-61%.These studies collectively indicate that AC and CM are effective sorbents for AMPA and could be used to reduce AMPA bioavailability from soil and AMPA residues in GM corn plants.展开更多
DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity.Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative...DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity.Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative effect.Natural products are a rich source of lead compounds for drug discovery,including anti-tumor drugs.In this study,we found that narciclasine(NCS),an amaryllidaceae alkaloid,is a novel inhibitor of topoisomerase I(topo I).Our data demonstrated that NCS inhibited topo I activity and reversed its unwinding effect on p-HOT DNA substrate.However,it had no obvious effect on topo II activity.The molecular mechanism of NCS inhibited topo I showed that NCS did not stabilize topo-DNA covalent complexes in cells,indicating that NCS is not a topo I poison.A blind docking result showed that NCS could bind to topo I,suggesting that NCS might be a topo I suppressor.Additionally,NCS exhibited a potent anti-proliferation effect in various cancer cells.NCS arrested the cell cycle at G_(2)/M phase and induced cell apoptosis.Our study reveals the antitumor mechanisms of NCS and provides a good foundation for the development of anti-cancer drugs based on topo I inhibition.展开更多
PD-1/PD-L1 inhibitors have emerged as standard treatments for advanced solid tumors;however,challenges such as a low overall response rate and systemic side effects impede their implementation.Hypoxia drives the remod...PD-1/PD-L1 inhibitors have emerged as standard treatments for advanced solid tumors;however,challenges such as a low overall response rate and systemic side effects impede their implementation.Hypoxia drives the remodeling of the tumor microenvironment,which is a leading reason for the failure of immunotherapies.Despite some reported strategies to alleviate hypoxia,their individual limitations constrain further improvements.Herein,a novel two-pronged strategy is pre-sented to efficiently address hypoxia by simultaneously adopting atovaquone(ATO,inhibiting oxygen consumption)and oxyhemoglobin(HbO2,directly supplement-ing oxygen)within a multifunctional aggregate termed NPs-aPD-1/HbO2/ATO.In addition to eliminating hypoxia with these two components,this smart aggre-gate also includes albumin and an ROS-responsive cross-linker as a controlled release scaffold,along with PD-1 antibody(aPD-1)for immunotherapy.Intriguingly,NPs-aPD-1/HbO2/ATO demonstrates exceptional tumor targeting in vivo,exhibit-ing≈4.2 fold higher accumulation in tumors than in the liver.Consequently,this aggregate not only effectively mitigates hypoxia and significantly assists aPD-1 immunotherapy but also simultaneously resolves the targeting and systemic toxicity issues associated with individual administration of each component.This study pro-poses substantial implications for drug-targeted delivery,addressing tumor hypoxia and advancing immunotherapy,providing valuable insights for advancing cancer treatment strategies.展开更多
The incidence of mycotoxin occurrence throughout the entire lifespan of some agricultural products could be due to climatic conditions and environmental factors(including high temperature,drought,and heavy rainfall)th...The incidence of mycotoxin occurrence throughout the entire lifespan of some agricultural products could be due to climatic conditions and environmental factors(including high temperature,drought,and heavy rainfall)that enhance growth of fungi.Deoxynivalenol(DON)which is also referred to as vomi-toxin is a mycotoxin produced from many Fusarium species.DON ranks high among the prominent mycotoxins in cereal products and is a ubiquitous toxin in livestock feeds.DON's adverse effects present major health challenges in both livestock and humans.The use of natural sorbents including smectite clays,is an economically feasible strategy to mitigate mycotoxin toxicities.Previous studies have demonstrated the potential of edible clays as protective components of human food and animal feed to alleviate toxicity associated with short-term exposure to mycotoxins including DON.Hence,this study was designed to investigate the sorption mechanisms of DON onto the binding surfaces of beidellite clay,assessing essential binding parameters such as enthalpy,free energy,binding capacity,affinity,and plateau surface density.These markers were used to predict availability of DON under the experimental conditions.Furthermore,the protection of beidellite clay against DON-induced toxicity was carried out using living organisms susceptible to DON toxicity,including Hydra vulgaris and Lemna minor.These studies investigated the dose-dependent detoxification of DON by 0.05-2%inclusion of beidellite.Beidellite exhibited more than 75%protection in Lemna minor and 53%in Hydra vulgaris validating that this clay is effective in detoxifying DON.During emergencies,or after disasters,inclusion of edible clay like beidellite in food,water or capsules could reduce bioavailability of DON and halt potential exposures to humans and animals.展开更多
基金supported by funding through NIEHS P42ES027704,R43 ES035325,and K99ES034090,and USDA Hatch6215。
文摘The co-occurrence of glyphosate(GLP)and aminomethylphosphonic acid(AMPA)in contaminated water,soil,sediment and plants is a cause for concern due to potential threats to the ecosystem and human health.A major route of exposure is through contact with contaminated soil and consumption of crops containing GLP and AMPA residues.However,clay-based sorption strategies for mixtures of GLP and AMPA in soil,plants and garden produce have been very limited.In this study,in vitro soil and in vivo genetically modified corn models were used to establish the proof of concept that the inclusion of clay sorbents in contaminated soils will reduce the bioavailability of GLP and AMPA in soils and their adverse effects on plant growth.Effects of chemical concentration(1–10 mg/kg),sorbent dose(0.5%-3%in soil and 0.5%-1%in plants)and duration(up to 28 days)on sorption kinetics were studied.The time course results showed a continuous GLP degradation to AMPA.The inclusion of calcium montmorillonite(CM)and acid processed montmorillonite(APM)clays at all doses significantly and consistently reduced the bioavailability of both chemicals from soils to plant roots and leaves in a dose-and time-dependent manner without detectable dissociation.Plants treated with 0.5%and 1%APM inclusion showed the highest growth rate(p≤0.05)and lowest chemical bioavailability with up to 76%reduction in roots and57%reduction in leaves.Results indicated that montmorillonite clays could be added as soil supplements to reduce hazardous mixtures of GLP and AMPA in soils and plants.
基金the Postgraduate Innovation Fund project of Anhui University of Science and Technology(2019CX2006)the National Natural Science Foundation of China(41773100)+1 种基金a Research Project of Huaibei Mining Group Co.(2020)a Research Project of Wanbei Coal-Electricity Group Co.,Ltd.(2020).
文摘The aim of this study is to evaluate the hydrogeochemical characteristics and water environmental quality of shallow groundwater in the Suxian mining area of Huaibei coalfield,China.The natural formation process of shallow groundwater in Suxian is explored using Piper trilinear charts and Gibbs diagrams,and by examining the ratios between the major ions.United States Salinity Laboratory(USSL)charts,Wilcox diagrams,and the water quality index(WQI)are further employed to quantify the differences in water quality.The results reveal that the main hydrochemical facies of groundwater are HC03-Ca,and that silicate dissolution is the main factor controlling the ion content in shallow groundwater.The USSL charts and Wilcox diagrams show that most of the water samples would be acceptable for use in irrigation systems.The WQI results for each water sample are compared and analyzed,and the quality of groundwater samples around collapse ponds is found to be relatively poor.
基金This work was supported by the National Science Fund for Excellent Young Scholars(21922813)and Key Research Program of Frontier Sciences of CAS(QYZDB-SSWSLH022)+2 种基金National Key Projects for Fundamental Research and Development of China(2017YFB0603301)DNL Cooperation Fund,CAS(DNL180202)and Youth Innovation Promotion Association of CAS(2017066).The authors sincerely appreciate Prof.Suojiang Zhang(IPE,CAS)for his careful academic guidance and great support.
文摘The cycloaddition of CO2 with epoxides catalyzed by ionic liquids(ILs)has been a widely ongoing studied hot topic over the years.Recent experimental research has shown that the protic ionic liquids(PILs)behave stronger hydrogen proton donating ability than aprotic ionic liquids(APILs),and can effectively catalyze the cycloaddition of CO2.Unfortunately,the mechanistic explanation remains primarily unraveled.Herein,a detailed simulation study on the cycloaddition reaction catalyzed by PIL([HDBU][Mim])in comparison with APIL([MeDBU][Mim])re-action catalysts was conducted,including the three-step route(ring-opening of PO(propylene oxide),insertion of CO2 and ring-closure of propylene carbonate(PC))and two-step route(simultaneously ring-opening of PO and addition of CO2,and then ring-closure of PC).Based on the activation energy barrier of the rate-determining step,PIL preferentially activates PO as the optimal route for the reaction with the energy barrier of 23.2 kcal mol-1,while that of APIL is 31.2 kcal mol-1.The role of[HDBU]+in the reaction was also explored and found that the direct formation of intermolecular hydrogen bond(H-bond)between[HDBU]+and the reactants(PO+CO2)was unfavorable for the reaction,while the cooperation with the anion[Mim]-to assist indirectly was more conducive.To fully consider the reaction microenvironment of ILs,ONIOM calculation was used to study the solvent effect.At last,the above conclusions were further verified by the analysis of intermediates with charge,non-covalent interaction(NCI),and atoms in molecules(AIM)methods.The computational findings show that ILs studied in this work have dual functions of catalyst and solvent,enabling a microscopic understanding of the ILs catalyst for CO2 utilization as well as providing guidance for the rational design of more efficient ILs-based catalysts.
基金funding through NIEHS SRP(Superfund Hazardous Substance Research and Training Program),P42 ES0277704,and USDA Hatch 6215。
文摘The widespread use of pesticides has resulted in detectable residues throughout the environment,sometimes at concentrations well above regulatory limits.Therefore,the development of safe,effective,field-practical,and economically feasible strategies to mitigate the effects of pesticides is warranted.Glyphosate is an organophosphorus herbicide that is degraded to aminomethylphosphonic acid(AMPA),a toxic and persistent metabolite that can accumulate in soil and sediment and translocate to plants.In this study,we investigated the binding efficacy of activated carbon(AC)and calcium montmorillonite(CM)clay to decrease AMPA bioavailability from soil and AMPA translocation to plants.Adsorption isotherms and thermodynamic studies on AC and CM were conducted and showed tight binding(enthalpy values>-20 k J/mol)for AMPA with high capacities(0.25 mol/kg and 0.38 mol/kg,respectively),based on derivations from the Langmuir model.A hydra assay was utilized to indicate toxicity of AMPA and the inclusion of 1%AC and CM both resulted in 90%protection of the hydra(**p≤0.01).Further studies in glyphosate-contaminated soil showed that AC and CM significantly reduced AMPA bioavailability by 53%and 44%,respectively.Results in genetically modified(GM)corn showed a conversion of glyphosate to AMPA in roots and sprouts over a 10-day exposure duration.Inclusion of AC and CM reduced AMPA residues in roots and sprouts by 47%-61%.These studies collectively indicate that AC and CM are effective sorbents for AMPA and could be used to reduce AMPA bioavailability from soil and AMPA residues in GM corn plants.
基金the National Natural Science Foundation of China(Grant Nos.21907044,81460559 and 82160697)Yunnan Fundamental Research Projects(Grant Nos.202101AT070155 and 202201AS070086)+2 种基金Basic Research Plan of Yunnan Provincial Science and Technology Department-Kunming Medical University(Grant Nos.202101AY070001-011,202201AY070001-003 and 202101AY070001-041)the Ten Thousand Talent Plans for Young Top-notch Talents of Yunnan Province(Hongyu Zhou,Dandan Liu),Yunnan Academician Expert Workstation(Grant No.202305AF150054)Basic Research Project of Yunnan Provincial Department of Education(Grant No.2022J0213).
文摘DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity.Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative effect.Natural products are a rich source of lead compounds for drug discovery,including anti-tumor drugs.In this study,we found that narciclasine(NCS),an amaryllidaceae alkaloid,is a novel inhibitor of topoisomerase I(topo I).Our data demonstrated that NCS inhibited topo I activity and reversed its unwinding effect on p-HOT DNA substrate.However,it had no obvious effect on topo II activity.The molecular mechanism of NCS inhibited topo I showed that NCS did not stabilize topo-DNA covalent complexes in cells,indicating that NCS is not a topo I poison.A blind docking result showed that NCS could bind to topo I,suggesting that NCS might be a topo I suppressor.Additionally,NCS exhibited a potent anti-proliferation effect in various cancer cells.NCS arrested the cell cycle at G_(2)/M phase and induced cell apoptosis.Our study reveals the antitumor mechanisms of NCS and provides a good foundation for the development of anti-cancer drugs based on topo I inhibition.
基金supported by the National Natural Science Foundation of China(Nos.82073058,32371449)Basic Research Projects of the Natural Science Foundation of Shaanxi Province(key program)(2021JZ-37)+2 种基金Youth Cultivation Project of the First Affiliated Hospital of Xi’an Jiaotong University(No.2019QN-02)Nanjing Tianqing Research Fund Project(No.HX202324)the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University,China(No.XJTU1AF-CRF-2022-009).
文摘PD-1/PD-L1 inhibitors have emerged as standard treatments for advanced solid tumors;however,challenges such as a low overall response rate and systemic side effects impede their implementation.Hypoxia drives the remodeling of the tumor microenvironment,which is a leading reason for the failure of immunotherapies.Despite some reported strategies to alleviate hypoxia,their individual limitations constrain further improvements.Herein,a novel two-pronged strategy is pre-sented to efficiently address hypoxia by simultaneously adopting atovaquone(ATO,inhibiting oxygen consumption)and oxyhemoglobin(HbO2,directly supplement-ing oxygen)within a multifunctional aggregate termed NPs-aPD-1/HbO2/ATO.In addition to eliminating hypoxia with these two components,this smart aggre-gate also includes albumin and an ROS-responsive cross-linker as a controlled release scaffold,along with PD-1 antibody(aPD-1)for immunotherapy.Intriguingly,NPs-aPD-1/HbO2/ATO demonstrates exceptional tumor targeting in vivo,exhibit-ing≈4.2 fold higher accumulation in tumors than in the liver.Consequently,this aggregate not only effectively mitigates hypoxia and significantly assists aPD-1 immunotherapy but also simultaneously resolves the targeting and systemic toxicity issues associated with individual administration of each component.This study pro-poses substantial implications for drug-targeted delivery,addressing tumor hypoxia and advancing immunotherapy,providing valuable insights for advancing cancer treatment strategies.
基金supported by funding through NIEHS P42 ES027704,USDA Hatch 6215.
文摘The incidence of mycotoxin occurrence throughout the entire lifespan of some agricultural products could be due to climatic conditions and environmental factors(including high temperature,drought,and heavy rainfall)that enhance growth of fungi.Deoxynivalenol(DON)which is also referred to as vomi-toxin is a mycotoxin produced from many Fusarium species.DON ranks high among the prominent mycotoxins in cereal products and is a ubiquitous toxin in livestock feeds.DON's adverse effects present major health challenges in both livestock and humans.The use of natural sorbents including smectite clays,is an economically feasible strategy to mitigate mycotoxin toxicities.Previous studies have demonstrated the potential of edible clays as protective components of human food and animal feed to alleviate toxicity associated with short-term exposure to mycotoxins including DON.Hence,this study was designed to investigate the sorption mechanisms of DON onto the binding surfaces of beidellite clay,assessing essential binding parameters such as enthalpy,free energy,binding capacity,affinity,and plateau surface density.These markers were used to predict availability of DON under the experimental conditions.Furthermore,the protection of beidellite clay against DON-induced toxicity was carried out using living organisms susceptible to DON toxicity,including Hydra vulgaris and Lemna minor.These studies investigated the dose-dependent detoxification of DON by 0.05-2%inclusion of beidellite.Beidellite exhibited more than 75%protection in Lemna minor and 53%in Hydra vulgaris validating that this clay is effective in detoxifying DON.During emergencies,or after disasters,inclusion of edible clay like beidellite in food,water or capsules could reduce bioavailability of DON and halt potential exposures to humans and animals.
