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Antibody-drug conjugates: recent advances in conjugation and linker chemistries 被引量:55
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作者 Kyoji Tsuchikama Zhiqiang An 《Protein & Cell》 SCIE CAS CSCD 2018年第1期33-46,共14页
The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potenti... The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potential to make a paradigm shift in cancer chemother- apy. This new antibody-based molecular platform enables selective delivery of a potent cytotoxic payload to target cancer cells, resulting in improved efficacy, reduced systemic toxicity, and preferable pharmacokinetics (PK)I pharmacodynamics (PD) and biodistribution compared to traditional chemotherapy. Boosted by the successes of FDA-approved Adcetris~ and Kadcyla~, this drug class has been rapidly growing along with about 60 ADCs cur- rently in clinical trials. In this article, we briefly review molecular aspects of each component (the antibody, payload, and linker) of ADCs, and then mainly discuss traditional and new technologies of the conjugation and linker chemistries for successful construction of clini- cally effective ADCs. Current efforts in the conjugation and linker chemistries will provide greater insights into molecular design and strategies for clinically effective ADCs from medicinal chemistry and pharmacology standpoints. The development of site-specific conjuga- tion methodologies for constructing homogeneous ADCs is an especially promising path to improving ADC design, which will open the way for novel cancer therapeutics. 展开更多
关键词 antibody-drug conjugates cancer chemotherapy CONJUGATION LINKER site-specific conjugation
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基于特定场地污染概念模型的健康风险评估案例研究 被引量:39
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作者 钟茂生 姜林 +4 位作者 姚珏君 夏天翔 朱笑盈 韩丹 张丽娜 《环境科学》 EI CAS CSCD 北大核心 2013年第2期647-652,共6页
对某有机化工厂地下水下游方向拟建设的地铁站所在区域土壤及地下水开展污染调查,结果表明,拟建地铁站区域深层土壤及地下水均被1,2-二氯乙烷污染,其中,土壤样品最高浓度104.08 mg·kg-1,位于地表以下8.6 m深处;地下水样品最高浓度1... 对某有机化工厂地下水下游方向拟建设的地铁站所在区域土壤及地下水开展污染调查,结果表明,拟建地铁站区域深层土壤及地下水均被1,2-二氯乙烷污染,其中,土壤样品最高浓度104.08 mg·kg-1,位于地表以下8.6 m深处;地下水样品最高浓度18 500μg·L-1.污染主要由位于上游的有机化工厂生产排污所致.本研究依据调查结果并结合地铁站的特殊结构设计构建了该场地特定的污染概念模型,推导了相应的风险计算公式用于计算站内人员的健康风险,并与基于通用污染概念模型建立的风险计算公式的评价结果进行比较.两种模型计算结果均表明该区域土壤及地下水中污染对未来地铁站工作人员造成的致癌风险将远高于目前普遍接受的风险水平(1×10-6),但前者计算的土壤和地下水对未来地铁工作人员造成的致癌风险要比后者分别高2倍和1.5倍.由此可见,对于具体的场地评价项目,应考虑场地的污染特性及未来建筑的结构特性对现有评估模型进行修正后进行健康风险评估,以避免因直接套用现有导则中的计算模型使最终评估结果偏离客观实际. 展开更多
关键词 特定场地 结构设计 污染概念模型 健康风险评价 案例研究
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Trends in cancer mortality in China from 2004 to 2018:A nationwide longitudinal study 被引量:36
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作者 Dongming Jiang Lijuan Zhang +9 位作者 Wenbin Liu Yibo Ding Jianhua Yin Rongbing Ren Qi Li Yifan Chen Jiaying Shen Xiaojie Tan Hongwei Zhang Guangwen Cao 《Cancer Communications》 SCIE 2021年第10期1024-1036,共13页
Background:The long-term trend in cancer death in a rapidly developing country provides information for cancer prophylaxis.Here,we aimed to identify the trends in cancer mortality in China during the 2004-2018 period.... Background:The long-term trend in cancer death in a rapidly developing country provides information for cancer prophylaxis.Here,we aimed to identify the trends in cancer mortality in China during the 2004-2018 period.Methods:Using raw data from the national mortality surveillance system of China,we assessed the mortalities of all cancer and site-specific cancers during the 2004-2018 period.The participants were divided into three age groups:≥65 years,40-64 years,and≤39 years.Changing trends in cancer death by gender,residency,and tumor location were estimated using fitting joinpoint models to log-transformed crude mortality rates(CMRs)and age-standardizedmortality rates(ASMRs).Results:Cancer death accounted for 24% of all-cause of death in China during 2014-2018.The CMR of all cancer was 150.0 per 100,000 persons.Cancer was the leading cause of death in the population<65 years.The six major cancer types(lung/bronchus cancer,liver cancer,stomach cancer,esophagus cancer,colorectal cancer,and pancreas cancer)accounted for 75.85% of all cancer deaths.The CMR of all cancer increased while the ASMR decreased during 2014-2018(P<0.001).Lung/bronchus cancer and liver cancer were the leading causes of cancer death in the population<65 years,accounting for 45.31%(CMR)and 44.35%(ASMR)of all cancer death,respectively.The ASMR of liver cancer was higher in the 40-64 years population than in the≥65 years population,in contrast to the other five major cancers.The ASMRs of liver cancer,stomach cancer,and esophagus cancer decreased although they were higher in rural residents than in urban residents;the ASMRs of lung/bronchus cancer,colorectal cancer,and pancreas cancer increased in rural residents although they were higher in urban residents than in rural residents during 2014-2018.Conclusion:Although the ASMR of all cancer decreased in China during 2004-2018,lung/bronchus cancer and liver cancer remained the leading causes of cancer-related premature death.Lung/bronchus cancer,colorectal cancer,and pancreas cancer increase 展开更多
关键词 age-standardized mortality rate breast cancer colorectal cancer crude mortality rate demographic distribution liver cancer national mortality surveillance system premature death site-specific cancer stomach cancer trend
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生物正交标记反应研究进展 被引量:14
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作者 杨麦云 陈鹏 《化学学报》 SCIE CAS CSCD 北大核心 2015年第8期783-792,共10页
对活体生物大分子进行特异性标记是一项具有挑战性的工作,它要求这类化学反应能够在生理条件下高效特异地进行,不会与生物体系中存在的各种活性物质发生副反应.最近十几年开发的生物正交反应能够比较好地满足这些要求,它们在生物分子标... 对活体生物大分子进行特异性标记是一项具有挑战性的工作,它要求这类化学反应能够在生理条件下高效特异地进行,不会与生物体系中存在的各种活性物质发生副反应.最近十几年开发的生物正交反应能够比较好地满足这些要求,它们在生物分子标记方面的应用拓展了我们对细胞内生物体系的理解.主要介绍那些应用广泛且可以用于活体细胞标记的生物正交反应.重点介绍通过位点特异性引入生物正交官能团来进行选择性标记细胞内目标蛋白质的策略.同时,我们根据使用催化剂类型对这些生物正交反应进行分类,并且列表比较它们的差异,以便于研究者挑选合适的反应.最后对生物正交反应的开发和进一步应用进行了展望. 展开更多
关键词 生物正交反应 活体细胞 蛋白质标记 位点特异性 非天然氨基酸
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Recombinase-mediated Gene Stacking as a Transformation Operating System 被引量:12
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作者 David W.Ow 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2011年第7期512-519,共8页
The current method for combining transgenes into a genome is through the assortment of independent loci, a classical operating system compatible with transgenic traits created by different developers, at different tim... The current method for combining transgenes into a genome is through the assortment of independent loci, a classical operating system compatible with transgenic traits created by different developers, at different times and/or through different transformation techniques. However, as the number of transgenic loci increases over time, increasingly larger populations are needed to find the rare individual with the desired assortment of transgenic loci along with the non-transgenic elite traits. Introducing a transgene directly into a field cultivar would bypass the need to introgress the engineered trait. However, this necessitates separate transformations into numerous field cultivars, along with the characterization and regulatory approval of each independent transformation event. Reducing the number of segregating transgenic loci could be achieved if multiple traits are introduced at the same time, a preferred option if each of the many traits is new or requires re-engineering. If reengineering of previously introduced traits is not needed, then appending a new trait to an existing locus would be a rational strategy. The insertion of new DNA at a known locus can be accomplished by site- specific integration, through a host-dependent homology-based process, or a heterologous site-specific recombination system. Here, we discuss gene stacking through the use of site-specific recombinases. 展开更多
关键词 site-specific recombination transgenic plants DNA integration marker removal CRE-LOX
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Spatial Variability of Soil Chemical Properties in the Reclaiming Marine Foreland to Yellow Sea of China 被引量:11
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作者 WEI Yi-chang BAI You-lu +3 位作者 JIN Ji-yun ZHANG Fang ZHANG Li-ping LIU Xiao-qiang 《Agricultural Sciences in China》 CAS CSCD 2009年第9期1103-1111,共9页
Precise information about the spatial variability of soil properties is essential in developing site-specific soil management, such as variable rate application of fertilizers. In this study the sampling grid of 100 m... Precise information about the spatial variability of soil properties is essential in developing site-specific soil management, such as variable rate application of fertilizers. In this study the sampling grid of 100 m × 100 m was established to collect 1 703 soil samples at the depth of 0-20 cm, and examine spatial patterns including 13 soil chemical properties (pH, OM, NH4^+, P, K, Ca, Mg, S, B, Cu, Fe, Mn, and Zn) in a 1 760 ha rice field in Haifeng farm, China, from 6th to 22nd of April, 2006, before fertilizer application and planting. Soil analysis was performed by ASI (Agro Services International) and data were analyzed both statistically and geostatistically. Results showed that the contents of soil OM, NH4^+, and Zn in Haifeng farm were very low for rice production and those of others were enough to meet the need for rice cultivation. The spatial distribution model and spatial dependence level for 13 soil chemical properties varied in the field. Soil Mg and B showed strong spatial variability on both descriptive statistics and geostatistics, and other properties showed moderate spatial variability. The maximum ranges for K, Ca, Mg, S, Cu and Mn were all - 3 990.6 m and the minimum ranges for soil pH, OM, NH4^+, P, Fe, and Zn ranged from 516.7 to 1 166.2 m. Clear patchy distribution of N, P, K, Mg, S, B, Mn, and Zn were found from their spatial distribution maps. This proved that sampling strategy for estimating variability should be adapted to the different soil chemical properties and field management. Therefore, the spatial variability of soil chemical properties with strong spatial dependence could be readily managed and a site-specific fertilization scheme for precision farming could be easily developed. 展开更多
关键词 soil property spatial variability geostatistcs site-specific fertilization precision farming
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国内外尾矿贮存堆放方法及应用 被引量:12
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作者 阎文庆 《金属矿山》 CAS 北大核心 2016年第9期1-14,共14页
尾矿是全球数量最大的工业废渣,对环境、生态、社会和矿山投资运营有巨大影响,其贮存堆放除传统尾矿库外,还有其他方法技术。针对目前国内外的尾矿贮存技术现状,从尾矿形态、堆放形式和贮存场地3个方面,归纳了尾矿贮存堆放的分类形式,... 尾矿是全球数量最大的工业废渣,对环境、生态、社会和矿山投资运营有巨大影响,其贮存堆放除传统尾矿库外,还有其他方法技术。针对目前国内外的尾矿贮存技术现状,从尾矿形态、堆放形式和贮存场地3个方面,归纳了尾矿贮存堆放的分类形式,并根据近几十年全球尾矿库事故资料,说明传统尾矿库的高风险性和高事故率;通过列举国内外使用过滤干堆、膏体堆放、水体内贮存及废渣混合堆放等方法的部分矿山,介绍了各贮存方法的应用特点、使用环境及选用各方法需要考虑的因素;讨论了地域特色、尾矿设备、环保标准和运营经济性等对尾矿贮存新技术推广的影响,认为在尾矿贮存的研究和应用上,我国同矿业强国比较,有进步也有不足;最后提出在经济适用前提下,过滤尾矿干堆、膏体尾矿、胶结尾矿和组合技术等贮存方法,未来在我国还有发展空间。 展开更多
关键词 尾矿 贮存堆放方法 尾矿库 膏体 过滤干堆 地域特色 发展趋势
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乡村公共艺术发展思路 被引量:10
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作者 潘鲁生 《公共艺术》 2019年第6期27-28,共2页
本文阐述了公共艺术与在地的文化生活、乡村发展之间的关系,指出公众参与是乡村公共艺术在地性发展的关键,民众共享、乡风文明是乡村公共艺术发展的目标;提出了中国乡村公共艺术的发展思路,即推进公共艺术介入乡村建设,助推乡村振兴,构... 本文阐述了公共艺术与在地的文化生活、乡村发展之间的关系,指出公众参与是乡村公共艺术在地性发展的关键,民众共享、乡风文明是乡村公共艺术发展的目标;提出了中国乡村公共艺术的发展思路,即推进公共艺术介入乡村建设,助推乡村振兴,构建植根中国语境的公共艺术生态体系,发挥其精神提升与文化引领的作用,突出民生主体,健全"政府主导、艺术介入、社会协作、村民受益"的乡村公共艺术发展思路。 展开更多
关键词 公共艺术 乡村振兴 政府主导 在地性
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数字时代的艺术风险:公共艺术与大数据资本主义 被引量:9
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作者 张钟萄(文/图) 《公共艺术》 2020年第3期24-29,共6页
数字时代的公共艺术正面临公共空间的数字化转型,因而公共艺术与特定的物理场域之间的联系在渐渐变弱。这既改变了过去几十年公共艺术中重要的"场域特性",也会改变公共艺术自身的特征。本文试图以数字时代的公共空间转变为视... 数字时代的公共艺术正面临公共空间的数字化转型,因而公共艺术与特定的物理场域之间的联系在渐渐变弱。这既改变了过去几十年公共艺术中重要的"场域特性",也会改变公共艺术自身的特征。本文试图以数字时代的公共空间转变为视角,表明公共艺术正面临着数字时代的风险,一方面是基于公共艺术与物理场域及场域特性的关系发生了变化;另一方面,公共空间、展示平台与艺术内容在数字时代的变化,暗含着艺术实践平台和大数据资本主义相结合的可能。 展开更多
关键词 公共艺术 大数据资本主义 数字公共空间 场域特性
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Probing the active sites of site-specific nitrogen doping in metal-free graphdiyne for electrochemical oxygen reduction reactions 被引量:7
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作者 Xingzhu Chen Wee-Jun Ong +2 位作者 Zhouzhou Kong Xiujian Zhao Neng Li 《Science Bulletin》 SCIE EI CSCD 2020年第1期45-54,M0004,共11页
The development of highly active and low-cost catalysts for electrochemical reactions is one of the most attractive topics in the renewable energy technology.Herein,the site-specific nitrogen doping of graphdiyne(GDY)... The development of highly active and low-cost catalysts for electrochemical reactions is one of the most attractive topics in the renewable energy technology.Herein,the site-specific nitrogen doping of graphdiyne(GDY)including grap-N,sp-N(Ⅰ)and sp-N(Ⅱ)GDY is systematically investigated as metal-free oxygen reduction electrocatalysts via density functional theory(DFT).Our results indicate that the doped nitrogen atom can significantly improve the oxygen(O2)adsorption activity of GDY through activating its neighboring carbon atoms.The free-energy landscape is employed to describe the electrochemical oxygen reduction reaction(ORR)in both O2 dissociation and association mechanisms.It is revealed that the association mechanism can provide higher ORR onset potential than dissociation mechanism on most of the substrates.Especially,sp-N(Ⅱ)GDY exhibits the highest ORR electrocatalytic activity through increasing the theoretical onset potential to 0.76 V.This work provides an atomic-level insight for the electrochemical ORR mechanism on metal-free N-doped GDY. 展开更多
关键词 Graphdiyne(GDY) site-specific nitrogen doping Metal-free catalysts Oxygen reduction reaction(ORR)
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Genome editing opens a new era of genetic improvement in polyploid crops 被引量:7
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作者 Qamar U.Zaman Chao Li +1 位作者 Hongtao Cheng Qiong Hu 《The Crop Journal》 SCIE CAS CSCD 2019年第2期141-150,共10页
Sequence-specific nucleases(SSN) that generate double-stranded DNA breaks(DSBs) in genes of interest are the key to site-specific genome editing in plants. Genome editing has developed into one method of reducing unde... Sequence-specific nucleases(SSN) that generate double-stranded DNA breaks(DSBs) in genes of interest are the key to site-specific genome editing in plants. Genome editing has developed into one method of reducing undesirable traits in crops by the induction of knockout mutations. Different SSN-mediated genome-editing systems, including LAGLIDADG homing endonucleases or meganucleases, zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats, are emerging as robust tools for introducing functional mutations in polyploid crops including citrus, wheat, cotton, soybean, rapeseed, potato, grapes, Camelina sativa,dandelion, and tobacco. The approach utilizes knowledge of biological mechanisms for targeted induction of DSBs and their error-prone repair, allowing highly specific changes at designated genome loci. In this review, we briefly describe genome-editing technologies and their application to genetic improvement of polyploid crops. 展开更多
关键词 GENOME EDITING CRISPR site-specific MUTAGENESIS POLYPLOID Crop improvement
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Effects of Site-Specific Nitrogen Management on Yield and Dry Matter Accumulation of Rice from Cold Areas of Northeastern China 被引量:7
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作者 PENG Xian-long LIU Yuan-ying +3 位作者 LUO Sheng-guo FAN Li-chun SONG Tian-xing GUO Yan-wen 《Agricultural Sciences in China》 CAS CSCD 2007年第6期715-723,共9页
The effects of yield increase and mechanism of site-specific nitrogen management (SSNM) in five rice varieties from cold areas of northeastern China were studied. Plot experiment for critical SPAD value and experime... The effects of yield increase and mechanism of site-specific nitrogen management (SSNM) in five rice varieties from cold areas of northeastern China were studied. Plot experiment for critical SPAD value and experiments of two fertilization methods, SSNM and farmer's fertilization practice (FFP) were conducted to study their effects on the quality and dry matter accumulation of rice population, as well as N uptake. Compared with FFP, SSNM significantly decreased the average N rate by 33.8%, significantly increased average ear-bearing tiller rate and LAI for grain-filling stage by 12.3% and 14.1-27.6%, correspondingly, improved dry matter weight and N uptake after heading period by 4.3-29.1% and 11.8-55.1% (P 〈 0.05), and heightened recovery efficiency and agronomic efficiency by 38.5-133.4% (P 〈 0.05) and 39.8-194.3% (P 〈 0.05), respectively, as well as increased the average yield by 9.8% in 2004 and 2005. The results indicated that the accumulation rate of dry matter and N increased the rice yield and N use efficiency, because of improving rice population quality and increasing LAI after heading period. 展开更多
关键词 cold areas RICE site-specific nitrogen management YIELD dry matter N use efficiency
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Recent advances in enzyme-mediated peptide ligation 被引量:6
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作者 Silin Xu Zhenguang Zhao Junfeng Zhao 《Chinese Chemical Letters》 SCIE CAS CSCD 2018年第7期1009-1016,共8页
Artificial synthesis and site-specific modification of peptides and proteins has evolved into an indispensable tool for protein engineers and chemical biologists. Chemical and enzymatic approaches to peptide ligation ... Artificial synthesis and site-specific modification of peptides and proteins has evolved into an indispensable tool for protein engineers and chemical biologists. Chemical and enzymatic approaches to peptide ligation are important alternatives of recombinant DNA technology for protein synthesis and modification. Although as old as that of chemical procedures, enzyme-mediated peptide ligation is far less developed than that of chemical counterpart due to the difficult availability of peptide ligase.Fortunately, this situation has been changed slowly with the fast development of biological techniques. In the past decades, several natural peptide ligases have been discovered. Protein engineering to improve the ligation efficiencies of the natural peptide ligase and to reverse the functionality of protease provide more powerful peptide ligases. In this review, the advances of enzyme-mediated peptide ligation and their application in protein synthesis and modification will be discussed. 展开更多
关键词 LIGASE Peptide synthesis Protein engineering Enzyme-mediated peptide ligation site-specific protein modification
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Conditional gene manipulation:Cre-ating a new biological era 被引量:7
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作者 Jian ZHANG Jing ZHAO +3 位作者 Wen-jie JIANG Xi-wei SHAN Xiao-mei YANG Jian-gang GAO 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2012年第7期511-524,共14页
To solve the problem of embryonic lethality in conventional gene knockouts, site-specific recombinase (SSR) systems (Cre-loxP, FIp-FRT, and φC31) have been used for tissue-specific gene knockout. With the combina... To solve the problem of embryonic lethality in conventional gene knockouts, site-specific recombinase (SSR) systems (Cre-loxP, FIp-FRT, and φC31) have been used for tissue-specific gene knockout. With the combination of an SSR system and inducible gene expression systems (tetracycline and tamoxifen), stage-specific knockout and transgenic expression can be achieved. The application of this "SSR+inducible" conditional tool to genomic manipulation can be extended in various ways. Alternatives to conditional gene targeting, such as conditional gene trapping, multipurpose conditional alleles, and conditional gene silencing, have been developed. SSR systems can also be used to construct precise disease models with point mutations and chromosomal abnormalities. With these exciting achievements, we are moving towards a new era in which the whole genome can be manipulated as we wish. 展开更多
关键词 site-specific recombinase Gene targeting Gene trapping Inducible systems φC31 system
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Spatial variability of soil properties in red soil and its implications for site-specific fertilizer management 被引量:6
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作者 SONG Fang-fang XU Ming-gang +5 位作者 DUAN Ying-hua CAI Ze-jiang WEN Shi-lin CHEN Xian-ni SHI Wei-qi Gilles COLINET 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2020年第9期2313-2325,共13页
Assessing spatial variability and mapping of soil properties constitute important prerequisites for soil and crop management in agricultural areas. To explore the relationship between soil spatial variability and land... Assessing spatial variability and mapping of soil properties constitute important prerequisites for soil and crop management in agricultural areas. To explore the relationship between soil spatial variability and land management, 256 samples were randomly collected at two depths (surface layer 0–20 cm and subsurface layer 20–40 cm) under different land use types and soil parent materials in Yujiang County, Jiangxi Province, a red soil region of China. The pH, soil organic matter (SOM), total nitrogen (TN), cation exchange capacity (CEC), and base saturation (BS) of the soil samples were examined and mapped. The results indicated that soils in Yujiang were acidified, with an average pH of 4.87 (4.03–6.46) in the surface layer and 4.99 (4.03–6.24) in the subsurface layer. SOM and TN were significantly higher in the surface layer (27.6 and 1.50 g kg–1, respectively) than in the subsurface layer (12.1 and 0.70 g kg–1, respectively), while both CEC and BS were low (9.0 and 8.0 cmol kg–1, 29 and 38% for surface and subsurface layers, respectively). Paddy soil had higher pH (mean 4.99) than upland and forest soils, while soil derived from river alluvial deposits (RAD) had higher pH (mean 5.05) than the other three parent materials in both layers. Geostatistical analysis revealed that the best fit models were exponential for pH and TN, and spherical for BS in both layers, while spherical and Gaussian were the best fitted for SOM and CEC in the surface and subsurface layers. Spatial dependency varied from weak to strong for the different soil properties in both soil layers. The maps produced by selecting the best predictive variables showed that SOM, TN, and CEC had moderate levels in most parts of the study area. This study highlights the importance of site-specific agricultural management and suggests guidelines for appropriate land management decisions. 展开更多
关键词 spatial variability soil pH CEC BS site-specific fertilizer management
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Construction of Marker-Free GFP Transgenic Tobacco by Cre/lox Site-Specific Recombination System 被引量:4
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作者 SONG Hong-yuan REN Xue-song SI Jun LI Cheng-qiong SONG Ming 《Agricultural Sciences in China》 CAS CSCD 2008年第9期1061-1070,共10页
Marker-free GFP transgenic tobacco plants were constructed based on Cre/lox site-specific recombination system. A GFP gene was introduced into the tobacco genome using the Bar gene as a linked selectable marker flanke... Marker-free GFP transgenic tobacco plants were constructed based on Cre/lox site-specific recombination system. A GFP gene was introduced into the tobacco genome using the Bar gene as a linked selectable marker flanked by recombination sites in a directed orientation. The Bar gene expression box was subsequently excised from the plant genome by a strategy of Cre gene retransformation. After removal of the Cre-NPT Ⅱ locus by genetic segregation through self-cross, plants that incorporated only the GFP transgene were obtained. Transgenic tobacco plants mediated by Agrobacterium tumefaciens were obtained, which resisted herbicide Basta and GFP expressed well, then the Cre gene was subsequently introduced into 5 plants of them, respectively, by retransformation. The leaf disks from Cre transgenic plants were used to test the resistance to Basta on the medium with 8 mg L-1 of PPT. The results showed that few discs were able to regenerate normally, and the excision at 76-100% efficiency depended on individual retransformation events. Evidence for a precise recombination event was confirmed by cloning the nucleotides sequence surrounding the lox sites of the Basta sensitive plants. The result indicated that the excision event in the recombination sites was precise and conservative, without loss or alteration of any submarginal nucleotides of the recombination sites. Bar gene excised plants were selfpollinated to allow segregation of the GFP gene from the Cre-NPT Ⅱ locus. The progenies from self-pollinated plants were scored for Kan senstivity, then the segregation of GFP gene from Cre-NPT Ⅱ locus in the Kan senstive plants were confirmed by PCR analysis subsequently. Hence, constructing marker-free transgenic tobacco plants by Cre/lox sitespecific recombination system was reliable, and the strategy presented here should be applicable to other plants for the construction of marker-free transgenic plants as well. 展开更多
关键词 Cre/lox site-specific recombination system marker-free transgenic tobacco GFP
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Changes in Grain Yield of Rice and Emission of Greenhouse Gases from Paddy Fields after Application of Organic Fertilizers Made from Maize Straw 被引量:4
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作者 MA Yi-hu GU Dao-jian +3 位作者 LIU Li-jun WANG Zhi-qin ZHANG Hao YANG Jian-chang 《Rice science》 SCIE 2014年第4期224-232,共9页
A field experiment was conducted at the farm of Yangzhou University, Yangzhou, China, to study the effects of organic fertilizers made from maize straw on rice grain yield and the emission of greenhouse gases. Four or... A field experiment was conducted at the farm of Yangzhou University, Yangzhou, China, to study the effects of organic fertilizers made from maize straw on rice grain yield and the emission of greenhouse gases. Four organic fertilizer treatments were as follows: maize straw (MS), compost made from maize straw (MC), methane-generating maize residue (MR), and black carbon made from maize straw (BC). These organic fertilizers were applied separately to paddy fields before rice transplanting. No organic fertilizer was applied to the control (CK). The effects of each organic fertilizer on rice grain yield and emission of greenhouse gases were investigated under two conditions, namely, no nitrogen (N) application (ON) and site-specific N management (SSNM). Rice grain yields were significantly higher in the MS, MC and MR treatments than those in CK under either ON or SSNM. The MS treatment resulted in the highest grain yield and agronomic N use efficiency. However, no significant difference was observed for these parameters between the BC treatment and CK. The changes in the emissions of methane (CH4) carbon dioxide (CO2), or nitrous oxide (N20) from the fields were similar among all organic fertilizer treatments during the entire rice growing season. The application of each organic fertilizer significantly increased the emission of each greenhouse gas (except N20 emission in the BC treatment) and global warming potential (GWP). Emissions of all the greenhouse gases and GWP increased under the same organic fertilizer treatment in the presence of N fertilizer, whereas GWP per unit grain yield decreased. The results indicate that the application of organic fertilizer (MS, MC or MR) could increase grain yield, but also could enhance the emissions of greenhouse gases from paddy fields. High grain yield and environmental efficiency could be achieved by applying SSNM with MR. 展开更多
关键词 organic fertilizer site-specific nitrogen management RICE grain yield greenhouse gas maize straw
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癌症治疗中新型抗体偶联药物的研究进展
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作者 李雨凝 苏佳琳 +2 位作者 谭树华 罗永忠 张乐蒙 《中南大学学报(医学版)》 CAS CSCD 北大核心 2024年第2期296-304,共9页
传统抗体偶联药物(antibody drug conjugates,ADC)通过将单克隆抗体与细胞毒性药物相结合,实现对癌细胞的精准打击,但在稳定性、靶向性、疗效及安全性等方面依然存在诸多不足。新型ADC,如双特异性、位点特异性、双有效载荷和前药型ADC,... 传统抗体偶联药物(antibody drug conjugates,ADC)通过将单克隆抗体与细胞毒性药物相结合,实现对癌细胞的精准打击,但在稳定性、靶向性、疗效及安全性等方面依然存在诸多不足。新型ADC,如双特异性、位点特异性、双有效载荷和前药型ADC,通过同时结合2个不同抗原或表位、选择更稳定的连接子、与抗体特定氨基酸位点偶联、携带不同药物有效载荷以及采用前药策略等优化方法,在保留传统ADC作用特点的基础上,显著提高药物的稳定性、靶向性、疗效和安全性,能更好地满足临床治疗的需求。新型ADC可能会在未来的癌症治疗中发挥重要的作用。探讨新型ADC在癌症治疗中的进展并分析其优势与挑战,可为开发抗癌策略提供理论支持,为药物研发提供方向。 展开更多
关键词 抗体偶联药物 癌症 双特异性 位点特异性 双有效载荷 前药型
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Peptide asparaginyl ligases——renegade peptide bond makers 被引量:2
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作者 James P.Tam Ning-Yu Chan +2 位作者 Heng Tai Liew Shaun J.Tan Yu Chen 《Science China Chemistry》 SCIE EI CAS CSCD 2020年第3期296-307,共12页
Making peptide bonds is tightly controlled by genetic code and machinery which includes cofactors,ATP,and RNAs.In this regard,the stand-alone and genetic-code-independent peptide ligases constitute a new family of ren... Making peptide bonds is tightly controlled by genetic code and machinery which includes cofactors,ATP,and RNAs.In this regard,the stand-alone and genetic-code-independent peptide ligases constitute a new family of renegade peptide-bond makers.A prime example is butelase-1,an Asn/Asp(Asx)-specific ligase that structurally belongs to the asparaginyl endopeptidase family.Butelase-1 specifically recognizes a C-terminal Asx-containing tripeptide motif,Asn/Asp-Xaa-Yaa(Xaa and Yaa are any amino acids),to form a site-specific Asn-Xaa peptide bond either intramolecularly as cyclic proteins or intermolecularly as modified proteins.Our work in the past five years has validated that butelase-1 is a potent and versatile ligase.Here we review the advances in ligases,with a focus on butelase-1,and their applications in engineering bioactive peptides and precision protein modifications,antibody-drug conjugates,and live-cell labeling. 展开更多
关键词 asparaginyl ENDOPEPTIDASE Asn-specific LIGATION bioorthogonal LIGATION butelase CHEMOENZYMATIC LIGATION live-cell LABELING PROTEIN engineering PROTEIN modification site-specific LABELING tandem LIGATION
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Remote Monitoring of Wheat Streak Mosaic Progression Using Sub-Pixel Classification of Landsat 5 TM Imagery for Site Specific Disease Management in Winter Wheat 被引量:3
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作者 Mustafa Mirik R. James Ansley +2 位作者 Jacob A. Price Fekede Workneh Charles M. Rush 《Advances in Remote Sensing》 2013年第1期16-28,共13页
Wheat streak mosaic (WSM), caused by Wheat streak mosaic virus is a viral disease that affects wheat (Triticum aestivum L.), other grains, and numerous grasses over large geographical areas around the world. To improv... Wheat streak mosaic (WSM), caused by Wheat streak mosaic virus is a viral disease that affects wheat (Triticum aestivum L.), other grains, and numerous grasses over large geographical areas around the world. To improve disease management and crop production, it is essential to have adequate methods for monitoring disease epidemics at various scales and multiple times. Remote sensing has become an essential tool for monitoring and quantifying crop stress due to biotic and abiotic factors. The objective of our study was to explore the utility of Landsat 5 TM imagery for detecting, quantifying, and mapping the occurrence of WSM in irrigated commercial wheat fields. The infection and progression of WSM was biweekly assessed in the Texas Panhandle during the 2007-2008 crop years. Diseased-wheat was separated from uninfected wheat on the images using a sub-pixel classifier. The overall classification accuracies were >91% with kappa coefficient between 0.80 and 0.94 for disease detection were achieved. Omission errors varied between 2% and 14%, while commission errors ranged from 1% to 21%. These results indicate that the TM image can be used to accurately detect and quantify disease for site-specific WSM management. Remote detection of WSM using geospatial imagery may substantially improve monitoring, planning, and management practices by overcoming some of the shortcomings of the ground-based surveys such as observer bias and inaccessibility. Remote sensing techniques for accurate disease mapping offer a unique set of advantages including repeatability, large area coverage, and cost-effectiveness over the ground-based methods. Hence, remote detection is particularly and practically critical for repeated disease mo- nitoring and mapping over time and space during the course of a growing season. 展开更多
关键词 WHEAT STREAK MOSAIC Virus Viral DISEASE Remote Sensing of DISEASE DISEASE Mapping WHEAT DISEASE site-specific DISEASE Management
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