Anthocyanins are important secondary metabolites in plants,but information on anthocyanin biosynthesis mechanisms in Chinese cabbage is limited.The new purple head Chinese cabbage cultivar 11S91 was analyzed,and an R2...Anthocyanins are important secondary metabolites in plants,but information on anthocyanin biosynthesis mechanisms in Chinese cabbage is limited.The new purple head Chinese cabbage cultivar 11S91 was analyzed,and an R2R3-MYB regulatory gene BrMYB2,located on chromosome A07,controlling the dominant purple-head trait was isolated.High expression of BrMYB2 generated a large accumulation of anthocyanins in 11S91,accompanied by highly upregulated BrTT8,BrF3′H,BrDFR1,BrANS1,BrUGTs,BrATs,and BrGSTs.11S91 inherited the purple locus from purple trait donor 95T2-5,and they shared consensus CDSs and gDNAs with those of BrMYB2(cBrMYB2 and gBrMYB2).Two SNPs in cBrMYB2 in 11S91 did not cause loss of function;in addition to several SNPs at both ends of intron 1,a large deletion had occurred in intron 1 of gBrMYB2 in 11S91.Genetic transformation of Arabidopsis showed that gBrMYB2 overexpression lines presented deeper purple color and higher expression than did the cBrMYB2 and cBrmyb2 lines,whereas gBrmyb2 with a long intron 1 did not cause the purple phenotype.We first show that BrMYB2 promotes anthocyanin biosynthesis under the control of the short intron 1 of gBrMYB2 in purple head Chinese cabbage,and gBrmyb2 with a long intron 1 represses anthocyanin production in white head Chinese cabbage.This evidence provides a new understanding of anthocyanin biosynthesis and purple germplasm generation in Brassica vegetables.展开更多
Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor ...Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.展开更多
All-solid-state lithium batteries are considered as the priority candidates for next-generation energy storage devices due to their better safety and higher energy density.As the key part of solid-state batteries,soli...All-solid-state lithium batteries are considered as the priority candidates for next-generation energy storage devices due to their better safety and higher energy density.As the key part of solid-state batteries,solid-state electrolytes have made certain research progress in recent years.Among the various types of solid-state electrolytes,sulfide electrolytes have received extensive attention because of their high roomtemperature ionic conductivity and good moldability.However,sulfide-based solid-state batteries are still in the research stage.This situation is mainly due to the fact that the application of sulfide electrolytes still faces challenges in particular of interfacial issues,mainly including chemical and electrochemical instability,unstable interfacial reaction,and solid-solid physical contact between electrolyte and electrode.Here,this review provides a comprehensive summary of the existing interfacial issues in the fabrication of sulfide-based solid-state batteries.The in-depth mechanism of the interfacial issues and the current research progress of the main coping strategies are discussed in detail.Finally,we also present an outlook on the future development of sulfide-based solid-state batteries to guide the rational design of nextgeneration high-energy solid-state batteries.展开更多
Gasoline compression ignition(GCI)combustion faces problems such as high maximum pressure rise rate(MPRR)and combustion deterioration at high loads.This paper aims to improve the engine performance of the GCI mode by ...Gasoline compression ignition(GCI)combustion faces problems such as high maximum pressure rise rate(MPRR)and combustion deterioration at high loads.This paper aims to improve the engine performance of the GCI mode by regulating concentration stratification and promoting fuel-gas mixing by utilizing the double main-injection(DMI)strategy.Two direct injectors simultaneously injected gasoline with an octane number of 82.7 to investigate the energy ratio between the two main-injection and exhaust gas recirculation(EGR)on combustion and emissions.High-load experiments were conducted using the DMI strategy and compared with the single main-injection(SMI)strategy and conventional diesel combustion.The results indicate that the DMI strategy have a great potential to reduce the MPRR and improve the fuel economy of the GCI mode.At a 10 bar indicated mean effective pressure,increasing the main-injection-2 ratio(Rm-2)shortens the injection duration and increases the mean mixing time.Optimized Rm-2 could moderate the trade-off between the MPRR and the indicated specific fuel consumption with both reductions.An appropriate EGR should be adopted considering combustion and emissions.The DMI strategy achieves a highly efficient and stable combustion at high loads,with an indicated thermal efficiency(ITE)greater than 48%,CO and THC emissions at low levels,and MPRR within a reasonable range.Compared with the SMI strategy,the maximum improvement of the ITE is 1.5%,and the maximum reduction of MPRR is 1.5 bar/°CA.展开更多
Microbial natural products have been one of the most important sources for drug development.In the current postgenomic era,sequence-driven approaches for natural product discovery are becoming increasingly popular.Her...Microbial natural products have been one of the most important sources for drug development.In the current postgenomic era,sequence-driven approaches for natural product discovery are becoming increasingly popular.Here,we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities.Our method employs uvrA-like genes as genetic markers,which have been identified in the biosynthetic gene clusters(BGCs)of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers.Through systematic genomic analysis of gifted actinobacteria genera,identification of uvrA-like gene-containing BGCs,and targeted isolation of products from a BGC prioritized for metabolic analysis,we identified a new tetracycline-type DNA intercalator timmycins.Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation.展开更多
After almost 7 years of dormancy,Hunga Tonga-Hunga Haʻapai Volcano(HTHHV)erupted on December 20^(th),2021.HTHHV is located in the South Pacific Ocean,65 km north of Tongatapu,Tonga’s main island.The volcano erupted a...After almost 7 years of dormancy,Hunga Tonga-Hunga Haʻapai Volcano(HTHHV)erupted on December 20^(th),2021.HTHHV is located in the South Pacific Ocean,65 km north of Tongatapu,Tonga’s main island.The volcano erupted again violently on January 15^(th),2022,causing loud booms thatwere heard across the Pacific Ocean,ejecting 30 km-high ash clouds into the stratosphere,and triggering severe tsunamis;ash from the eruption caused communication networks to collapse.展开更多
基金supported by the National Natural Science Foundation of China(grant No.31672163)the National Key Research and Development Program of China(grant No.2017YFD0101802).
文摘Anthocyanins are important secondary metabolites in plants,but information on anthocyanin biosynthesis mechanisms in Chinese cabbage is limited.The new purple head Chinese cabbage cultivar 11S91 was analyzed,and an R2R3-MYB regulatory gene BrMYB2,located on chromosome A07,controlling the dominant purple-head trait was isolated.High expression of BrMYB2 generated a large accumulation of anthocyanins in 11S91,accompanied by highly upregulated BrTT8,BrF3′H,BrDFR1,BrANS1,BrUGTs,BrATs,and BrGSTs.11S91 inherited the purple locus from purple trait donor 95T2-5,and they shared consensus CDSs and gDNAs with those of BrMYB2(cBrMYB2 and gBrMYB2).Two SNPs in cBrMYB2 in 11S91 did not cause loss of function;in addition to several SNPs at both ends of intron 1,a large deletion had occurred in intron 1 of gBrMYB2 in 11S91.Genetic transformation of Arabidopsis showed that gBrMYB2 overexpression lines presented deeper purple color and higher expression than did the cBrMYB2 and cBrmyb2 lines,whereas gBrmyb2 with a long intron 1 did not cause the purple phenotype.We first show that BrMYB2 promotes anthocyanin biosynthesis under the control of the short intron 1 of gBrMYB2 in purple head Chinese cabbage,and gBrmyb2 with a long intron 1 represses anthocyanin production in white head Chinese cabbage.This evidence provides a new understanding of anthocyanin biosynthesis and purple germplasm generation in Brassica vegetables.
基金supported by the National Key Research and Development Program of China‘Precision Medicine Research’(Grant No.2017YFC0908602)the State Key Program of National Natural Science of China(Grant No.81430081)National Key R&D Program of China(No.2017YFE0102200)。
文摘Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.
基金National Key Research and Development Program of China(2022YFB2404400)National Natural Science Foundation of China(22075025)+2 种基金funding from General Research Institute for Nonferrous Metals(C712620213102034)Science and Technology Program of Guangdong Province(grant no.32020B0909030004)Graduate Interdisciplinary Innovation Project of Yangtze Delta Region Academy of Beijing Institute of Technology(Jiaxing,no.GIIP2022-010).
文摘All-solid-state lithium batteries are considered as the priority candidates for next-generation energy storage devices due to their better safety and higher energy density.As the key part of solid-state batteries,solid-state electrolytes have made certain research progress in recent years.Among the various types of solid-state electrolytes,sulfide electrolytes have received extensive attention because of their high roomtemperature ionic conductivity and good moldability.However,sulfide-based solid-state batteries are still in the research stage.This situation is mainly due to the fact that the application of sulfide electrolytes still faces challenges in particular of interfacial issues,mainly including chemical and electrochemical instability,unstable interfacial reaction,and solid-solid physical contact between electrolyte and electrode.Here,this review provides a comprehensive summary of the existing interfacial issues in the fabrication of sulfide-based solid-state batteries.The in-depth mechanism of the interfacial issues and the current research progress of the main coping strategies are discussed in detail.Finally,we also present an outlook on the future development of sulfide-based solid-state batteries to guide the rational design of nextgeneration high-energy solid-state batteries.
基金supported by the National Key R&D Program of China(Grant No.2022YFE0100100).
文摘Gasoline compression ignition(GCI)combustion faces problems such as high maximum pressure rise rate(MPRR)and combustion deterioration at high loads.This paper aims to improve the engine performance of the GCI mode by regulating concentration stratification and promoting fuel-gas mixing by utilizing the double main-injection(DMI)strategy.Two direct injectors simultaneously injected gasoline with an octane number of 82.7 to investigate the energy ratio between the two main-injection and exhaust gas recirculation(EGR)on combustion and emissions.High-load experiments were conducted using the DMI strategy and compared with the single main-injection(SMI)strategy and conventional diesel combustion.The results indicate that the DMI strategy have a great potential to reduce the MPRR and improve the fuel economy of the GCI mode.At a 10 bar indicated mean effective pressure,increasing the main-injection-2 ratio(Rm-2)shortens the injection duration and increases the mean mixing time.Optimized Rm-2 could moderate the trade-off between the MPRR and the indicated specific fuel consumption with both reductions.An appropriate EGR should be adopted considering combustion and emissions.The DMI strategy achieves a highly efficient and stable combustion at high loads,with an indicated thermal efficiency(ITE)greater than 48%,CO and THC emissions at low levels,and MPRR within a reasonable range.Compared with the SMI strategy,the maximum improvement of the ITE is 1.5%,and the maximum reduction of MPRR is 1.5 bar/°CA.
基金the National Key R&D Program of China(2019YFA0905400)the National Natural Science Foundation of China(32122005).
文摘Microbial natural products have been one of the most important sources for drug development.In the current postgenomic era,sequence-driven approaches for natural product discovery are becoming increasingly popular.Here,we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities.Our method employs uvrA-like genes as genetic markers,which have been identified in the biosynthetic gene clusters(BGCs)of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers.Through systematic genomic analysis of gifted actinobacteria genera,identification of uvrA-like gene-containing BGCs,and targeted isolation of products from a BGC prioritized for metabolic analysis,we identified a new tetracycline-type DNA intercalator timmycins.Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation.
文摘After almost 7 years of dormancy,Hunga Tonga-Hunga Haʻapai Volcano(HTHHV)erupted on December 20^(th),2021.HTHHV is located in the South Pacific Ocean,65 km north of Tongatapu,Tonga’s main island.The volcano erupted again violently on January 15^(th),2022,causing loud booms thatwere heard across the Pacific Ocean,ejecting 30 km-high ash clouds into the stratosphere,and triggering severe tsunamis;ash from the eruption caused communication networks to collapse.