New Delhi metallo-β-lactamase 1(NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relative...New Delhi metallo-β-lactamase 1(NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relatively weak due to the shallow active pocket of NDM-1. Alternatively, irreversible covalent inhibitors can prevent their dissociation from the target, leading to permanent inactivation of the protein.Herein, we report a series of irreversible covalent inhibitors of NDM-1 targeting the conserved Lys211 in the active pocket. Several methods, including mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorescent labeling, and coumarin probe were used to demonstrate that pentafluorophenyl ester formed a covalent bond with Lys211. Moreover, our target inhibitor, in combination with meropenem, achieved an antibacterial effect on drug-resistant bacteria, along with an excellent safety profile. Our new strategy in designing lysine-targeted irreversible covalent NDM-1 inhibitors provides a potential option for the clinical treatment of Gram-negative bacteria.展开更多
Nicotinamide phosphoribosyl transferase(NAMPT)is considered as a promising target for cancer therapy to its crucial role in cancer metabolism.Despite the therapeutic potential of NAMPT enzymatic inhibitors,their effec...Nicotinamide phosphoribosyl transferase(NAMPT)is considered as a promising target for cancer therapy to its crucial role in cancer metabolism.Despite the therapeutic potential of NAMPT enzymatic inhibitors,their effectiveness is limited by dose-related toxicity and the inability to suppress nonenzymatic functions of extracellular NAMPT(e NAMPT).Herein,we designed and synthesized the first hydrophobic tagging NAMPT degraders.Among them,compound NH-11 selectively degraded NAMPT in leukemia cells through the ubiquitin-proteasome system.Compound NH-11 effectively induced apoptosis and showed low toxicity to normal cells,representing a promising anti-leukemia lead compound.?2024 Published by Elsevier B.V.on behalf of Chinese Chemical Society and Institute of Materia Medica,Chinese Academy of Medical Sciences.展开更多
With Sunflower （ Helianthus annuus L.） as an experimental material, phytohormones were externally applied, so as to screen phytohormones capable of alleviating environmental stress. Three kinds of phytohormones （au...With Sunflower （ Helianthus annuus L.） as an experimental material, phytohormones were externally applied, so as to screen phytohormones capable of alleviating environmental stress. Three kinds of phytohormones （auxin IAA, gibberellin GA and salicylic acid SA） were added through pot culture. The results showed that the three phytohormones all improved the accumulation of ^88 Sr in sunflower plant, and increased the translocation and bioaccumulation factors of ^88 Sr; and under the 100 mg/LSA treatment, the adsorption capacity, TF and BCF of ^88 Sr in sunflower plant reached the highest values.展开更多
Oil-use peony is a treasure with broad prospects.Heze City plans to develop oil-use peony as a local key industry.However,there are still many urgent problems that need to be solved for the sustained and healthy devel...Oil-use peony is a treasure with broad prospects.Heze City plans to develop oil-use peony as a local key industry.However,there are still many urgent problems that need to be solved for the sustained and healthy development of the oil-use peony industry.This paper delved into the comprehensive benefits of oil-use peony and its industrial development from the aspects of cultivating high-quality germplasm resources,technological innovation,policy support,developing leading enterprises,improving industrialization system,comprehensive promotion,and strengthening storage and transportation technology,aiming to provide some reference for further development of Heze oil-use peony industry.展开更多
The peony industry is a characteristic industry in Heze City,and oil-use peony is an emerging industry.Heze City has planned oil-use peony as a key support and development industry in the local area.The oil-use peony ...The peony industry is a characteristic industry in Heze City,and oil-use peony is an emerging industry.Heze City has planned oil-use peony as a key support and development industry in the local area.The oil-use peony industry is full of treasures,but there are still many urgent problems to be solved for its sustained and healthy development:cultivation and planting,variety selection,product processing,and enterprise development,which have hindered the development of the oil-use peony industry.This paper delved into the comprehensive benefits of oil-use peony and its industrial development,providing some reference for the further development of the oil-use peony industry in Heze.展开更多
[Objectives]The effects of three exogenous phytohormones on the uptake and accumulation of Cd in the seedlings of Amaranthus mangostanus L.were investigated.[Methods]Three effective plant hormones,auxin(IAA),gibberell...[Objectives]The effects of three exogenous phytohormones on the uptake and accumulation of Cd in the seedlings of Amaranthus mangostanus L.were investigated.[Methods]Three effective plant hormones,auxin(IAA),gibberellin(GA)and salicylic acid(SA)were selected and formulated into three concentrations,respectively,and were studied through pot experiments.[Results]The application of IAA,GA and SA increased the accumulation of Cd in each part of A.mangostanus.The absorption capacities of Cd in the roots,stems and leaves of A.mangostanus were related to the types and levels of hormones,and the overall trend was GA>SA>IAA.The leaves had significantly higher Cd translocation and bioaccumulation capacities than the stems.Under the treatment of 500 mg/L low concentration of gibberellin,the translocation and bioaccumulation factors reached the highest.[Conclusions]The results indicated that the absorptive,accumulative and transferred capacities of Cd of the amaranth plants after using phytohormones were obviously higher than the control.展开更多
基金funded by the National Natural Science Foundation of China (No. 82073688 to X. Sun and No. 82103971 to Y. Liang)Science and Technology Commission of Shanghai Municipality (No. 21S11907300 to X. Sun)Shanghai Science and Technology Development Fund from Central Leading Local Government (No. YDZX20223100001004 to X. Sun)。
文摘New Delhi metallo-β-lactamase 1(NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relatively weak due to the shallow active pocket of NDM-1. Alternatively, irreversible covalent inhibitors can prevent their dissociation from the target, leading to permanent inactivation of the protein.Herein, we report a series of irreversible covalent inhibitors of NDM-1 targeting the conserved Lys211 in the active pocket. Several methods, including mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorescent labeling, and coumarin probe were used to demonstrate that pentafluorophenyl ester formed a covalent bond with Lys211. Moreover, our target inhibitor, in combination with meropenem, achieved an antibacterial effect on drug-resistant bacteria, along with an excellent safety profile. Our new strategy in designing lysine-targeted irreversible covalent NDM-1 inhibitors provides a potential option for the clinical treatment of Gram-negative bacteria.
基金supported by the National Key Research and Development Program of China(No.2022YFC3401500 to C.S.)the National Natural Science Foundation of China(No.82030105 to C.S.)and Shanghai Rising-Star Program(No.20QA1411700 to G.D.)。
文摘Nicotinamide phosphoribosyl transferase(NAMPT)is considered as a promising target for cancer therapy to its crucial role in cancer metabolism.Despite the therapeutic potential of NAMPT enzymatic inhibitors,their effectiveness is limited by dose-related toxicity and the inability to suppress nonenzymatic functions of extracellular NAMPT(e NAMPT).Herein,we designed and synthesized the first hydrophobic tagging NAMPT degraders.Among them,compound NH-11 selectively degraded NAMPT in leukemia cells through the ubiquitin-proteasome system.Compound NH-11 effectively induced apoptosis and showed low toxicity to normal cells,representing a promising anti-leukemia lead compound.?2024 Published by Elsevier B.V.on behalf of Chinese Chemical Society and Institute of Materia Medica,Chinese Academy of Medical Sciences.
文摘With Sunflower （ Helianthus annuus L.） as an experimental material, phytohormones were externally applied, so as to screen phytohormones capable of alleviating environmental stress. Three kinds of phytohormones （auxin IAA, gibberellin GA and salicylic acid SA） were added through pot culture. The results showed that the three phytohormones all improved the accumulation of ^88 Sr in sunflower plant, and increased the translocation and bioaccumulation factors of ^88 Sr; and under the 100 mg/LSA treatment, the adsorption capacity, TF and BCF of ^88 Sr in sunflower plant reached the highest values.
基金Supported by Social Science Planning Project of Heze City in 2022 (HSKGH[2022]3)Key Laboratory of Plant Biology,Heze University.
文摘Oil-use peony is a treasure with broad prospects.Heze City plans to develop oil-use peony as a local key industry.However,there are still many urgent problems that need to be solved for the sustained and healthy development of the oil-use peony industry.This paper delved into the comprehensive benefits of oil-use peony and its industrial development from the aspects of cultivating high-quality germplasm resources,technological innovation,policy support,developing leading enterprises,improving industrialization system,comprehensive promotion,and strengthening storage and transportation technology,aiming to provide some reference for further development of Heze oil-use peony industry.
基金Supported by Social Science Planning Project of Heze City in 2022(HSKGH[2022]3)。
文摘The peony industry is a characteristic industry in Heze City,and oil-use peony is an emerging industry.Heze City has planned oil-use peony as a key support and development industry in the local area.The oil-use peony industry is full of treasures,but there are still many urgent problems to be solved for its sustained and healthy development:cultivation and planting,variety selection,product processing,and enterprise development,which have hindered the development of the oil-use peony industry.This paper delved into the comprehensive benefits of oil-use peony and its industrial development,providing some reference for the further development of the oil-use peony industry in Heze.
文摘[Objectives]The effects of three exogenous phytohormones on the uptake and accumulation of Cd in the seedlings of Amaranthus mangostanus L.were investigated.[Methods]Three effective plant hormones,auxin(IAA),gibberellin(GA)and salicylic acid(SA)were selected and formulated into three concentrations,respectively,and were studied through pot experiments.[Results]The application of IAA,GA and SA increased the accumulation of Cd in each part of A.mangostanus.The absorption capacities of Cd in the roots,stems and leaves of A.mangostanus were related to the types and levels of hormones,and the overall trend was GA>SA>IAA.The leaves had significantly higher Cd translocation and bioaccumulation capacities than the stems.Under the treatment of 500 mg/L low concentration of gibberellin,the translocation and bioaccumulation factors reached the highest.[Conclusions]The results indicated that the absorptive,accumulative and transferred capacities of Cd of the amaranth plants after using phytohormones were obviously higher than the control.
