Flowering time is important for adaptation of soybean(Glycine max)to different environments.Here,we conducted a genome-wide association study of flowering time using a panel of 1490 cultivated soybean accessions.We id...Flowering time is important for adaptation of soybean(Glycine max)to different environments.Here,we conducted a genome-wide association study of flowering time using a panel of 1490 cultivated soybean accessions.We identified three strong signals at the qFT02-2 locus(Chr02:12037319–12238569),which were associated with flowering time in three environments:Gongzhuling,Mengcheng,and Nanchang.By analyzing linkage disequilibrium,gene expression patterns,gene annotation,and the diversity of variants,we identified an AP1 homolog as the candidate gene for the qFT02-2 locus,which we named GmAP1d.Only one nonsynonymous polymorphism existed among 1490 soybean accessions at position Chr02:12087053.Accessions carrying the Chr02:12087053-T allele flowered significantly earlier than those carrying the Chr02:12087053-A allele.Thus,we developed a cleaved amplified polymorphic sequence(CAPS)marker for the SNP at Chr02:12087053,which is suitable for marker-assisted breeding of flowering time.Knockout of GmAP1d in the‘Williams 82’background by gene editing promoted flowering under long-day conditions,confirming that GmAP1d is the causal gene for qFT02-2.An analysis of the region surrounding GmAP1d revealed that GmAP1d was artificially selected during the genetic improvement of soybean.Through stepwise selection,the proportion of modern cultivars carrying the Chr02:12087053-T allele has increased,and this allele has become nearly fixed(95%)in northern China.These findings provide a theoretical basis for better understanding the molecular regulatory mechanism of flowering time in soybean and a target gene that can be used for breeding modern soybean cultivars adapted to different latitudes.展开更多
Cytoplasmic male sterility(CMS)-restorer system is a useful tool to exploit heterosis in soybean.The major restorer gene for the M-type CMS is known as Rf-m,located in the 162.4-kb region on chromosome 16.Sequence ana...Cytoplasmic male sterility(CMS)-restorer system is a useful tool to exploit heterosis in soybean.The major restorer gene for the M-type CMS is known as Rf-m,located in the 162.4-kb region on chromosome 16.Sequence analysis has revealed that the Rf-m locus in Glycine max consists of seven penta tricopeptide repeat(GmPPR)genes.The deduced amino acid sequences contain 8 to 14 PPR motifs,and a phylogenetic analysis grouped these GmPPR proteins into two PPR subfamilies:Glyma.16G161800 belongs to the PLS subfamily,and the P subfamily consists.of Glyma.16G161900,Glyma 16G162000,Glyma.16G162100,Glyma.16G162700,Glyma.16G162800,and Gly-ma 16G163100.The phylogenetic analysis of seven GmPPR proteins and 27 other plant PPR proteins also showed that proteins in the same subfamilies cluster together.Comparative sequence analysis was conducted using the seven Rf-m candidate GmPPR genes from the sterile line W931A,the maintainer line W931B,and the restorer line WR016,the result showed that Glyma 16G161900 had higher polymorphism than the other candidate genes.Based on real-time quantitative RT-PCR data,all seven GmPPR genes were differentially expressed but showed constitutive expression in roots,stems,leaves,and pollen grains.Additionally,the expression level of Gly-ma 16G161900 in the sterile line W931 A was significantly higher in all tissues than in the restorer line WR016.Taken together,these results suggest that Glyma 16G161900 is the most likely candidate for the restorer gene Rf-m.This study is the first report and analysis of candidate fertility restorer(Rf)genes encoding PPR proteins in soybean.展开更多
This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.go...This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.展开更多
基金supported by the National Natural Science Foundation of China(U22A20473)the National Key Research and Development Program of China(2021YFD1201600)+2 种基金the China Agriculture Research System(CARS-04-PS01)the Agricultural Science and Technology Innovation Program(ASTIP)of Chinese Academy of Agricultural Sciences,Scientific Innovation 2030 Project(2022ZD0401703)the Platform of National Crop Germplasm Resources of China。
文摘Flowering time is important for adaptation of soybean(Glycine max)to different environments.Here,we conducted a genome-wide association study of flowering time using a panel of 1490 cultivated soybean accessions.We identified three strong signals at the qFT02-2 locus(Chr02:12037319–12238569),which were associated with flowering time in three environments:Gongzhuling,Mengcheng,and Nanchang.By analyzing linkage disequilibrium,gene expression patterns,gene annotation,and the diversity of variants,we identified an AP1 homolog as the candidate gene for the qFT02-2 locus,which we named GmAP1d.Only one nonsynonymous polymorphism existed among 1490 soybean accessions at position Chr02:12087053.Accessions carrying the Chr02:12087053-T allele flowered significantly earlier than those carrying the Chr02:12087053-A allele.Thus,we developed a cleaved amplified polymorphic sequence(CAPS)marker for the SNP at Chr02:12087053,which is suitable for marker-assisted breeding of flowering time.Knockout of GmAP1d in the‘Williams 82’background by gene editing promoted flowering under long-day conditions,confirming that GmAP1d is the causal gene for qFT02-2.An analysis of the region surrounding GmAP1d revealed that GmAP1d was artificially selected during the genetic improvement of soybean.Through stepwise selection,the proportion of modern cultivars carrying the Chr02:12087053-T allele has increased,and this allele has become nearly fixed(95%)in northern China.These findings provide a theoretical basis for better understanding the molecular regulatory mechanism of flowering time in soybean and a target gene that can be used for breeding modern soybean cultivars adapted to different latitudes.
基金the National Key Research and Development Program of China(Grant No.2016YFD0101503)the Key Research and Development Program of Anhui Province(Grant No.202004a06020034)+1 种基金the Major Science and Technology Project of Anhui Province(Grant No.18030701178)the Program on Industrial Technology System of National Soybean(Grant No.CARS-04-PS07)。
文摘Cytoplasmic male sterility(CMS)-restorer system is a useful tool to exploit heterosis in soybean.The major restorer gene for the M-type CMS is known as Rf-m,located in the 162.4-kb region on chromosome 16.Sequence analysis has revealed that the Rf-m locus in Glycine max consists of seven penta tricopeptide repeat(GmPPR)genes.The deduced amino acid sequences contain 8 to 14 PPR motifs,and a phylogenetic analysis grouped these GmPPR proteins into two PPR subfamilies:Glyma.16G161800 belongs to the PLS subfamily,and the P subfamily consists.of Glyma.16G161900,Glyma 16G162000,Glyma.16G162100,Glyma.16G162700,Glyma.16G162800,and Gly-ma 16G163100.The phylogenetic analysis of seven GmPPR proteins and 27 other plant PPR proteins also showed that proteins in the same subfamilies cluster together.Comparative sequence analysis was conducted using the seven Rf-m candidate GmPPR genes from the sterile line W931A,the maintainer line W931B,and the restorer line WR016,the result showed that Glyma 16G161900 had higher polymorphism than the other candidate genes.Based on real-time quantitative RT-PCR data,all seven GmPPR genes were differentially expressed but showed constitutive expression in roots,stems,leaves,and pollen grains.Additionally,the expression level of Gly-ma 16G161900 in the sterile line W931 A was significantly higher in all tissues than in the restorer line WR016.Taken together,these results suggest that Glyma 16G161900 is the most likely candidate for the restorer gene Rf-m.This study is the first report and analysis of candidate fertility restorer(Rf)genes encoding PPR proteins in soybean.
基金This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.(Nanjing,China)and was supported by grants from National Natural Science Foundation of China(Grant Number,81872902,82073917,and 82070206)National Natural Science Foundation of Guangdong Province(Grant Number,2023A1515011525)+1 种基金The Lymphoma Research Fund of China Anti-Cancer Association,and the Sun Yat-sen University Cancer Center Clinical Research 308 Program(Grant Number,2014-fxy-106 and 2016-fxy-079)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant Number,TJYXZDXK-053B).
文摘This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.
