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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
文摘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.
基金National Natural Science Foundation of China,Grant/Award Numbers:81673250,81520108021,91529305Key discipline fromthe“3-year public health promotion”programof Shanghai Municipal Health Commission。
文摘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
文摘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.
基金funded by thestarting project of scientific research for high-level tal-ents introduced by North China University of Water Conservancy and Electric Power (200723)Shang-hai Municipal Key Task Projects of Prospering Agri-culture by the Science and Technology Plan, China(NGZ 1-10)
文摘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.
基金financial supports by the Young Scientists Fund of the National Natural Science Foundation of China (11604249)the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161008)+3 种基金the Foundation of the State Key Laboratory of Optical Fiber and Cable Manufacture Technology (SKLD1602)the State Key Laboratory of Refractors and Metallurgy (G201605), the Fundamental Research Funds for the Central Universities (2019-III-034)the Research Board of the State Key Laboratory of Silicate Materials for Architecturesfinancial supports and grants from Xiamen University Malaysia,the Xiamen University Malaysia Research Fund (XMUMRF/2019-C3/ IENG/0013)
文摘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.
基金supported by the National Natural Science Foundation of China(No.31700316)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(Group No.118)+2 种基金the Earmarked Fund for China Agriculture Research System(CARS-12)the Fundamental Research Funds for Central Non-Profit Scientific Institution(1610172018009)Graduate School of Chinese Academy of Agricultural Sciences
文摘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.
文摘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.
基金The National Natural Science Foundation of China (Nos. 21462023, 21778025)the Education Department of Jiangxi Province (No.150297)
文摘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.
基金Project supported by the National Natural Science Foundation of China(Nos.30871436,30973297,and 31171194)the National Basic Research Program(973)of China(No.2010CB945002)+1 种基金the Ministry of Education of China(No.200804220011)Shandong Provincial Science and Technology Key Program(No.2009GG10003039),China
文摘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.
基金This study was supported by the National Natural Science Foundation of China(41620104006 and 41977104)the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences(1630062018005).We thank the staff from Yujiang Soil and Fertilizer Extension Station,Jiangxi,China for help with soil sampling.
文摘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.
基金the National Natural Science Foundation of China (30200185)the Science Foundation of Committee of Education of Chongqing Municipality,China (030208)
文摘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.
基金supported by the grants from the National Basic Research Program(Grant No.2009CB118603)the National Science Foundation of China(NSFC-IRRI Joint Research Project,Grant No.31061140457)+3 种基金the Natural Science Foundation of China(Grant Nos.31071360 and 31271641)the Basic Scientific Research Special Operation Cost of the Central Research Institutions(Grant Nos.201103003 and 201203079)the National Key Technology Support Program of China(Grant Nos.2011BAD16B14 and 2012BAD04B08)the Jiangsu Advantages of Key Construction Projects and Research Innovation Project by Graduate Student(Grant No.CXZZ13_0902)
文摘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.
文摘传统抗体偶联药物(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。
基金supported by Academic Research Grant Tier 3(MOE2016-T3-1-003)from the Singapore Ministry of Education.
文摘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.
文摘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.