城市电网在发生N-1故障后,极可能新增运行风险,导致N-1-1时出现大面积停电事故。为管控城市电网N-1后运行风险,该文提出一种改进双智能体竞争双深度Q网络(dueling double deep Q network,D3QN)的城市电网N-1风险管控转供策略。根据风险...城市电网在发生N-1故障后,极可能新增运行风险,导致N-1-1时出现大面积停电事故。为管控城市电网N-1后运行风险,该文提出一种改进双智能体竞争双深度Q网络(dueling double deep Q network,D3QN)的城市电网N-1风险管控转供策略。根据风险管控原则,提出一种无需额外历史数据、考虑备自投装置、单供变电站风险和单供负荷母线风险的N-1场景指标;建立计及动作次序、指标间关系的负荷转供三阶段求解模型。以含预动作-变化探索值选择策略的改进双智能体D3QN方法,将负荷转供分为多个子转供环节学习,使转供思路清晰化,对动作空间进行降维,提高训练寻优效果,得到管控N-1风险的负荷转供策略。通过城市电网多场景算例分析,验证该文模型和方法的有效性。展开更多
Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male s...Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death （PCD） as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling （TUNEL） and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species （O2- and H202） and down-regulation of the activities of superoxide dismutase （SOD）, catalase （CAT） and guaiacol peroxidase （POD）. Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.展开更多
Nicotinamide phosphoribosyltransferase(NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD^+, essential for a number of enzymes and regulatory proteins involved in a variety of cellular pro...Nicotinamide phosphoribosyltransferase(NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD^+, essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA(TSA) and β-lapachone(β-lap) induced a rapid depletion of NAD^+ pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death. Compared with TSA or β-lap treatment alone, co-treatment with FK866 induced a more dramatic depletion of NAD^+, repression of SIRT1 activity, and thereby the increased accumulation of acetylated FOXO1 and the activation of apoptotic pathway. In conclusion, the results from the present study support that NAMPT inhibition can synergize with NQO1 activation to induce apoptotic cell death, thereby providing a new rationale for the development of combinative therapeutic drugs in combating non-small lung cancer.展开更多
The ultrastructure of porcine kidney(PK)-15 cells was examined after lipofectamine-aided transfection of the molecular clone of the P1 agent.PK-15 cells transfected with the tandem dimer of the P1molecular DNA clone h...The ultrastructure of porcine kidney(PK)-15 cells was examined after lipofectamine-aided transfection of the molecular clone of the P1 agent.PK-15 cells transfected with the tandem dimer of the P1molecular DNA clone had numbers of intracytoplasmic inclusions,and a few cells had intranuclear inclusions.Intracytoplasmic inclusions were round to oval and 0.1-0.3μm in diameter,and intranuclear inclusions,which were more electron dense,were of two general types:the first were round and small(0.1μm approximately)and the second were hexagonal and larger(0.4-0.8μm in diameter).Cells transfected with the tandem dimer of the P1 molecular DNA clone tested positive for P1 DNA at passage 5.This is the first report that the P1 molecular clone has infectivity in vitro and it will provide fundamental materials for further study of the biological characterization of P1.展开更多
The tobacco Ralstonia Solanacearum were both cultured on nutrient agar plates and inoculated in seedling stage of tobacco, then treated with K1 and K2, two anti-bacterial agents, at a serial con-centrations to study t...The tobacco Ralstonia Solanacearum were both cultured on nutrient agar plates and inoculated in seedling stage of tobacco, then treated with K1 and K2, two anti-bacterial agents, at a serial con-centrations to study their inhibitory efficiency. The result indicated that K1 can inhibit R. Solanacearum growth entirely, at the concentration range from 1/50 to 1/5000. K2 can reach the same result at the concentration range from 1/50 to 1/50000. Compared with the control plates, K1, at the concentration 1/50000, had no significant differences, and the average number of colony per plate was 112-115. The immature tobacco shown wilt as soon as inoculated with R. Solanacearum, and recovered gradually after using K1, K2. The densities of microbial suspension, handled by K1, K2 within 10 hs, were both significantly lower than the controlled ones. The optical microscopy also shown that handled microbial body differed from the controlled, whose body was regular short, rod shape as opposed to the handled ones with irregular rod shape and damaged body. All the results indicated that K1 and K2 both had inhibitory effects on tobacco R. Solanacearum, and K2 was more efficient than K1.展开更多
为了筛选适宜塞外红苹果冷藏的保鲜袋,研究了在0~0.5℃的贮藏条件下,0.01、0.02、0.04mm厚度的PE(聚乙烯,polyethylene)保鲜袋结合1-甲基环丙烯(1-methylcyclopropene,1-MCP)缓释剂处理对果肉硬度、可溶性固形物含量、可滴定酸含量、外...为了筛选适宜塞外红苹果冷藏的保鲜袋,研究了在0~0.5℃的贮藏条件下,0.01、0.02、0.04mm厚度的PE(聚乙烯,polyethylene)保鲜袋结合1-甲基环丙烯(1-methylcyclopropene,1-MCP)缓释剂处理对果肉硬度、可溶性固形物含量、可滴定酸含量、外观及风味以及原果胶含量、可溶性果胶含量、纤维素含量、乙醇含量、乙醛含量、总抗氧化能力、过氧化氢含量等品质指标的影响。结果表明,与CK相比,不同厚度的保鲜袋结合1-MCP缓释剂处理均能有效延缓塞外红果肉硬度、可溶性固形物含量、可滴定酸含量的下降速度,抑制原果胶含量的降低和可溶性果胶含量的升高,延缓乙醇、乙醛高峰的出现时间,维持果实总抗氧化能力在较高的水平。综合比较认为:0.02 mm PE袋+1-MCP缓释剂和0.01 mm PE袋+1-MCP缓释剂2个处理的贮藏保鲜效果相对较好,贮藏120 d及货架5 d期间,能保持果实较好的硬度、外观及风味,有效延缓果实的衰老;0.04 mm PE保鲜袋贮藏的果实果皮出现褐变,而且果肉有异味,不适宜用于塞外红果实冷藏。展开更多
PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as...PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.展开更多
Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on...Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on cardiomyo-cyte injury.The structure of the newly synthesized compounds had been confirmed by 1H-NMR,13C-NMR,and HR-ESI-MS spectra.Among all target compounds at 1μM,compounds 9d,9f,9k,9m,and 9n,with a protection ratio exceeding 30%,exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A.Meanwhile,compounds 9k,9m,and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte,all with a dpHi/min value less than 0.23.What is more,compounds 9k,9m,9o and buthutin A all exhibited the specificity on NHE-1 inhibition.Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1,but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A.The structure-activity relationship(SAR)studies suggested that the presences of amide group,four-carbon linker,and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions.This research would open new avenues for developing amide-guanidine-based cardioprotective agents.展开更多
Exploration of immunosuppressive agents for the treatment of diabetes is a burgeoning field that has captured the attention of the medical community.The innovative approach of using these agents to combat diabetes is ...Exploration of immunosuppressive agents for the treatment of diabetes is a burgeoning field that has captured the attention of the medical community.The innovative approach of using these agents to combat diabetes is driven by their diverse capabilities to regulate the immune system,which is pivotal for disease pathogenesis.The primary objective is to enhance the management of blood glucose levels,which is a critical factor in the daily life of diabetic patients.This comprehensive review delves into the therapeutic horizons opened by immunosuppressive agents,particularly their potential impact on type 1 and type 2 diabetes mellitus,and their utility in the transplantation process.The complex etiology of diabetes,which involves a delicate interplay of genetic,environmental,and immunological factors,presents a multifaceted target landscape for these therapies.The agents discussed in the review,including CD3 inhibitors,cytotoxic T-lymphocyte-associated protein 4-immunoglobulin G,Janus kinase inhibitors,anti-thymocyte globulin,tumor necrosis factor-αinhibitors,CD20 inhibitors,alefacept,and alemtuzumab,each bring a unique mechanism to the table,offering a tailored approach to immune modulation.As research progresses,emphasis is being placed on evaluating the long-term efficacy and safety of these agents to pave the way for more personalized and effective diabetes management strategies.展开更多
文摘城市电网在发生N-1故障后,极可能新增运行风险,导致N-1-1时出现大面积停电事故。为管控城市电网N-1后运行风险,该文提出一种改进双智能体竞争双深度Q网络(dueling double deep Q network,D3QN)的城市电网N-1风险管控转供策略。根据风险管控原则,提出一种无需额外历史数据、考虑备自投装置、单供变电站风险和单供负荷母线风险的N-1场景指标;建立计及动作次序、指标间关系的负荷转供三阶段求解模型。以含预动作-变化探索值选择策略的改进双智能体D3QN方法,将负荷转供分为多个子转供环节学习,使转供思路清晰化,对动作空间进行降维,提高训练寻优效果,得到管控N-1风险的负荷转供策略。通过城市电网多场景算例分析,验证该文模型和方法的有效性。
基金supported by the National High Technology Research and Development Program of China (2011AA10A106)the National Natural Science Foundation of China (31171611, 31371697)+1 种基金the Technological Innovation and Over Planning Projects of Shaanxi Province, China (2014KTZB02-01-02, 2011KTZB02-01-01)the Projects Opening Up New Function of Precision Instrument of Northwest A&F University, China (dysb130210)
文摘Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death （PCD） as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling （TUNEL） and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species （O2- and H202） and down-regulation of the activities of superoxide dismutase （SOD）, catalase （CAT） and guaiacol peroxidase （POD）. Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.
基金supported by the National Natural Science Foundation of China(Nos.81430091,81325025,and 81273586)Jiangsu Provincial Promotion Foundation for the Key Lab of Drug Metabolism and Pharmacokinetics(No.BM2012012)the Natural Science Foundation of Jiangsu Province for Outstanding Youth Scholar(No.BK2012026)
文摘Nicotinamide phosphoribosyltransferase(NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD^+, essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA(TSA) and β-lapachone(β-lap) induced a rapid depletion of NAD^+ pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death. Compared with TSA or β-lap treatment alone, co-treatment with FK866 induced a more dramatic depletion of NAD^+, repression of SIRT1 activity, and thereby the increased accumulation of acetylated FOXO1 and the activation of apoptotic pathway. In conclusion, the results from the present study support that NAMPT inhibition can synergize with NQO1 activation to induce apoptotic cell death, thereby providing a new rationale for the development of combinative therapeutic drugs in combating non-small lung cancer.
基金supported by the State Key Basic Research Project(973 project)of China(Grant No.2007CB116308)Planned Projects for Postdoctoral Research Funds of Jiangsu Province,China(Grant No.5910602)Postdoctoral Funds of Jiangsu Academy of Agricultural Sciences,China(Grant No.6510501)
文摘The ultrastructure of porcine kidney(PK)-15 cells was examined after lipofectamine-aided transfection of the molecular clone of the P1 agent.PK-15 cells transfected with the tandem dimer of the P1molecular DNA clone had numbers of intracytoplasmic inclusions,and a few cells had intranuclear inclusions.Intracytoplasmic inclusions were round to oval and 0.1-0.3μm in diameter,and intranuclear inclusions,which were more electron dense,were of two general types:the first were round and small(0.1μm approximately)and the second were hexagonal and larger(0.4-0.8μm in diameter).Cells transfected with the tandem dimer of the P1 molecular DNA clone tested positive for P1 DNA at passage 5.This is the first report that the P1 molecular clone has infectivity in vitro and it will provide fundamental materials for further study of the biological characterization of P1.
文摘The tobacco Ralstonia Solanacearum were both cultured on nutrient agar plates and inoculated in seedling stage of tobacco, then treated with K1 and K2, two anti-bacterial agents, at a serial con-centrations to study their inhibitory efficiency. The result indicated that K1 can inhibit R. Solanacearum growth entirely, at the concentration range from 1/50 to 1/5000. K2 can reach the same result at the concentration range from 1/50 to 1/50000. Compared with the control plates, K1, at the concentration 1/50000, had no significant differences, and the average number of colony per plate was 112-115. The immature tobacco shown wilt as soon as inoculated with R. Solanacearum, and recovered gradually after using K1, K2. The densities of microbial suspension, handled by K1, K2 within 10 hs, were both significantly lower than the controlled ones. The optical microscopy also shown that handled microbial body differed from the controlled, whose body was regular short, rod shape as opposed to the handled ones with irregular rod shape and damaged body. All the results indicated that K1 and K2 both had inhibitory effects on tobacco R. Solanacearum, and K2 was more efficient than K1.
文摘为了筛选适宜塞外红苹果冷藏的保鲜袋,研究了在0~0.5℃的贮藏条件下,0.01、0.02、0.04mm厚度的PE(聚乙烯,polyethylene)保鲜袋结合1-甲基环丙烯(1-methylcyclopropene,1-MCP)缓释剂处理对果肉硬度、可溶性固形物含量、可滴定酸含量、外观及风味以及原果胶含量、可溶性果胶含量、纤维素含量、乙醇含量、乙醛含量、总抗氧化能力、过氧化氢含量等品质指标的影响。结果表明,与CK相比,不同厚度的保鲜袋结合1-MCP缓释剂处理均能有效延缓塞外红果肉硬度、可溶性固形物含量、可滴定酸含量的下降速度,抑制原果胶含量的降低和可溶性果胶含量的升高,延缓乙醇、乙醛高峰的出现时间,维持果实总抗氧化能力在较高的水平。综合比较认为:0.02 mm PE袋+1-MCP缓释剂和0.01 mm PE袋+1-MCP缓释剂2个处理的贮藏保鲜效果相对较好,贮藏120 d及货架5 d期间,能保持果实较好的硬度、外观及风味,有效延缓果实的衰老;0.04 mm PE保鲜袋贮藏的果实果皮出现褐变,而且果肉有异味,不适宜用于塞外红果实冷藏。
文摘PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.
基金supported by the National Natural Science Foundation of China(NSFC)Youth Project(No.82204397).
文摘Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on cardiomyo-cyte injury.The structure of the newly synthesized compounds had been confirmed by 1H-NMR,13C-NMR,and HR-ESI-MS spectra.Among all target compounds at 1μM,compounds 9d,9f,9k,9m,and 9n,with a protection ratio exceeding 30%,exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A.Meanwhile,compounds 9k,9m,and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte,all with a dpHi/min value less than 0.23.What is more,compounds 9k,9m,9o and buthutin A all exhibited the specificity on NHE-1 inhibition.Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1,but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A.The structure-activity relationship(SAR)studies suggested that the presences of amide group,four-carbon linker,and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions.This research would open new avenues for developing amide-guanidine-based cardioprotective agents.
基金Supported by The National Natural Science Foundation of China,No.82273986Natural Science Foundation of Zhejiang Province,No.LYY22H310014.
文摘Exploration of immunosuppressive agents for the treatment of diabetes is a burgeoning field that has captured the attention of the medical community.The innovative approach of using these agents to combat diabetes is driven by their diverse capabilities to regulate the immune system,which is pivotal for disease pathogenesis.The primary objective is to enhance the management of blood glucose levels,which is a critical factor in the daily life of diabetic patients.This comprehensive review delves into the therapeutic horizons opened by immunosuppressive agents,particularly their potential impact on type 1 and type 2 diabetes mellitus,and their utility in the transplantation process.The complex etiology of diabetes,which involves a delicate interplay of genetic,environmental,and immunological factors,presents a multifaceted target landscape for these therapies.The agents discussed in the review,including CD3 inhibitors,cytotoxic T-lymphocyte-associated protein 4-immunoglobulin G,Janus kinase inhibitors,anti-thymocyte globulin,tumor necrosis factor-αinhibitors,CD20 inhibitors,alefacept,and alemtuzumab,each bring a unique mechanism to the table,offering a tailored approach to immune modulation.As research progresses,emphasis is being placed on evaluating the long-term efficacy and safety of these agents to pave the way for more personalized and effective diabetes management strategies.
