Doubled haploid(DH)technology is an efficient method used in commercial maize breeding.Chromosome doubling is a vital step of DH technology;however,the underlying processes regulating chromosome doubling of haploid is...Doubled haploid(DH)technology is an efficient method used in commercial maize breeding.Chromosome doubling is a vital step of DH technology;however,the underlying processes regulating chromosome doubling of haploid is still not well understood,which is key to optimize the technology.In this study,the immature haploid embryos of the maize inbred line Zheng58 treated with amiprophos-methyl(APM)or colchicine were used to analyze transcriptomic and metabolomic changes,75 and 60 differential expressed metabolites(DEMs)were identified between control treatment,respectively.Most differentially expressed genes(DEGs)related to artificial chromosome doubling were down regulated;these were mainly involved in mitosis process.Both DEMs and DEGs co-expression analyses showed that,compared to controls,zeatin biosynthesis and cofactor and vitamin metabolism were significantly enriched in both APM and colchicine treatments.In a parallel experiment,exogenous vitamins including thiamine,nicotinic acid,vitamin B6,or trans-zeatin were added to colchicine treatment;there were synergistic effects between vitamins or zeatin and colchicine in haploid artificial chromosome doubling.These results provide novel insights in exploring the molecular responses to antimitotic reagents at both the transcriptomic and metabolomic levels.In addition,the application efficiency of haploid breeding will be greatly improved by the key factors for artificial chromosome doubling.展开更多
Cyanobacteria attracted much attention recently because of their secondary metaboliteswith potent biological activities and unusual structures. This paper reviews some recent studies on the iso-lation, structural, elu...Cyanobacteria attracted much attention recently because of their secondary metaboliteswith potent biological activities and unusual structures. This paper reviews some recent studies on the iso-lation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteriaNostoc species.展开更多
Aptamers serve as unique targeting ligands,making aptamer-drug conjugates(ApDCs)an attractive strategy for targeted cancer therapy.This study performs a comprehensive evaluation from rodents to non-human primates(NHP)...Aptamers serve as unique targeting ligands,making aptamer-drug conjugates(ApDCs)an attractive strategy for targeted cancer therapy.This study performs a comprehensive evaluation from rodents to non-human primates(NHP)of a protein tyrosine kinase 7(PTK7)-targeted ApDC(Sgc8c-M)made by conjugating the potent antimitotic agent monomethyl auristatin E(MMAE)to the classic PTK7 aptamer Sgc8c.Efficacy studies in various cancer types with PTK7 overexpression showed that Sgc8c-M effectively induces sustained tumor regression in cell line-derived and patient-derived xenografts,outperforming unconjugated MMAE,the chemotherapy drug paclitaxel,and a PTK7-targeted antibody-drug conjugate.Pharmacokinetic(PK)studies in mice revealed that Sgc8c-M leads to rapid accumulation and sustained MMAE levels in tumors,along with fast clearance from plasma and normal tissues.Further study in rats confirmed rapid clearance across most organs and revealed that over 75%of MMAE was excreted through urine and feces within 24 h.Toxicokinetic(TK)assessments indicated comparable systemic drug exposure without accumulation for repeated doses compared to single administration.Toxicity evaluations showed that the therapeutic dose with high efficacy was safe and that the toxicity resulting from extremely high doses could be reversibly controlled.Encouraged by these findings,we evaluated PK/TK profiles and safety of Sgc8c-M in cynomolgus monkeys.Similar to PK/TK profiles observed in rats,Sgc8c-M demonstrated good dose-dependent drug exposure.It was,moreover,well tolerated in monkeys with no obvious accumulation following multiple administrations.These findings highlight the potential of Sgc8c-M as an effective antitumor agent and provide useful insights for the clinical translation of emerging ApDCs.展开更多
基金supported by the Science and Technology Innovation 2030-Major Project (2023ZD0403001)China Agriculture Research System (CARS-02)+3 种基金Beijing Academy of Agriculture and Forestry Sciences Excellent Scientist Training Program (JKZX202202)National Natural Science Foundation of China (32001554)Beijing Academy of Agriculture and Forestry Sciences Science and Technology Innovation Capability Improvement Project (KJCX20230103)Chinese Universities Scientific Fund (2022TC141).
文摘Doubled haploid(DH)technology is an efficient method used in commercial maize breeding.Chromosome doubling is a vital step of DH technology;however,the underlying processes regulating chromosome doubling of haploid is still not well understood,which is key to optimize the technology.In this study,the immature haploid embryos of the maize inbred line Zheng58 treated with amiprophos-methyl(APM)or colchicine were used to analyze transcriptomic and metabolomic changes,75 and 60 differential expressed metabolites(DEMs)were identified between control treatment,respectively.Most differentially expressed genes(DEGs)related to artificial chromosome doubling were down regulated;these were mainly involved in mitosis process.Both DEMs and DEGs co-expression analyses showed that,compared to controls,zeatin biosynthesis and cofactor and vitamin metabolism were significantly enriched in both APM and colchicine treatments.In a parallel experiment,exogenous vitamins including thiamine,nicotinic acid,vitamin B6,or trans-zeatin were added to colchicine treatment;there were synergistic effects between vitamins or zeatin and colchicine in haploid artificial chromosome doubling.These results provide novel insights in exploring the molecular responses to antimitotic reagents at both the transcriptomic and metabolomic levels.In addition,the application efficiency of haploid breeding will be greatly improved by the key factors for artificial chromosome doubling.
文摘Cyanobacteria attracted much attention recently because of their secondary metaboliteswith potent biological activities and unusual structures. This paper reviews some recent studies on the iso-lation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteriaNostoc species.
基金funded by the National Key Research and Development Program of China(2023YFC3405100)the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2023SDYXS0001 and 2025C01109)+2 种基金the Zhejiang Provincial Natural Science Foundation of China(LDQ24B020002 and LDQ23B050001)the National Natural Science Foundation of China(No.22104132)the Zhejiang Province“Kunpeng Action”Program.
文摘Aptamers serve as unique targeting ligands,making aptamer-drug conjugates(ApDCs)an attractive strategy for targeted cancer therapy.This study performs a comprehensive evaluation from rodents to non-human primates(NHP)of a protein tyrosine kinase 7(PTK7)-targeted ApDC(Sgc8c-M)made by conjugating the potent antimitotic agent monomethyl auristatin E(MMAE)to the classic PTK7 aptamer Sgc8c.Efficacy studies in various cancer types with PTK7 overexpression showed that Sgc8c-M effectively induces sustained tumor regression in cell line-derived and patient-derived xenografts,outperforming unconjugated MMAE,the chemotherapy drug paclitaxel,and a PTK7-targeted antibody-drug conjugate.Pharmacokinetic(PK)studies in mice revealed that Sgc8c-M leads to rapid accumulation and sustained MMAE levels in tumors,along with fast clearance from plasma and normal tissues.Further study in rats confirmed rapid clearance across most organs and revealed that over 75%of MMAE was excreted through urine and feces within 24 h.Toxicokinetic(TK)assessments indicated comparable systemic drug exposure without accumulation for repeated doses compared to single administration.Toxicity evaluations showed that the therapeutic dose with high efficacy was safe and that the toxicity resulting from extremely high doses could be reversibly controlled.Encouraged by these findings,we evaluated PK/TK profiles and safety of Sgc8c-M in cynomolgus monkeys.Similar to PK/TK profiles observed in rats,Sgc8c-M demonstrated good dose-dependent drug exposure.It was,moreover,well tolerated in monkeys with no obvious accumulation following multiple administrations.These findings highlight the potential of Sgc8c-M as an effective antitumor agent and provide useful insights for the clinical translation of emerging ApDCs.
