Alfalfa(Medicago sativa L.)is the most widely grown forage legume crop worldwide.Yield and plant height are important agronomic traits influenced by genetic and environmental factors.The objective of this study was to...Alfalfa(Medicago sativa L.)is the most widely grown forage legume crop worldwide.Yield and plant height are important agronomic traits influenced by genetic and environmental factors.The objective of this study was to identify quantitative trait loci(QTL)and molecular markers associated with alfalfa yield and plant height.To understand the genetic basis of these traits,a full-sib F1 population composed of 392 individuals was developed by crossing a low-yielding precocious alfalfa genotype(male parent)with a high-yielding latematuring alfalfa cultivar(female parent).The linkage maps were constructed with 3818 single-nucleotide polymorphism(SNP)markers on 64 linkage groups.QTL for yield and plant height were mapped using phenotypic data for three years.Sixteen QTL associated with yield and plant height were identified on chromosomes 1 to 8.Six QTL explained more than 10%of phenotypic variation,representing major loci controlling yield and plant height.One locus on chromosome 1 controlling yield traits had not been identified in previous studies.Three QTL co-located with other QTL(qyield-1 and qheight-7,qheight-5 and qyield-4,qheight-6,and qyield-6).With further validation,the markers closely linked with these QTL may be used for marker-assisted selection in breeding new alfalfa varieties with high yield.展开更多
Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognize...Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.展开更多
Given the escalating impact of climate change on agriculture and food security,gaining insights into the evolutionary dynamics of climatic adaptation and uncovering climate-adapted variation can empower the breeding o...Given the escalating impact of climate change on agriculture and food security,gaining insights into the evolutionary dynamics of climatic adaptation and uncovering climate-adapted variation can empower the breeding of climate-resilient crops to face future climate change.Alfalfa(Medicago sativa subsp.sativa),the queen of forages,shows remarkable adaptability across diverse global environments,making it an excellent model for investigating species responses to climate change.In this study,we performed population genomic analyses using genome resequencing data from 702 accessions of 24 Medicago species to unravel alfalfa’s climatic adaptation and genetic susceptibility to future climate change.We found that interspecific genetic exchange has contributed to the gene pool of alfalfa,particularly enriching defense and stress-response genes.Intersubspecific introgression between M.sativa subsp.falcata(subsp.falcata)and alfalfa not only aids alfalfa’s climatic adaptation but also introduces genetic burden.A total of 1671 genes were associated with climatic adaptation,and 5.7%of them were introgressions from subsp.falcata.By integrating climate-associated variants and climate data,we identified populations that are vulnerable to future climate change,particularly in higher latitudes of the Northern Hemisphere.These findings serve as a clarion call for targeted conservation initiatives and breeding efforts.We also identified preadaptive populations that demonstrate heightened resilience to climate fluctuations,illuminating a pathway for future breeding strategies.Collectively,this study enhances our understanding about the local adaptation mechanisms of alfalfa and facilitates the breeding of climate-resilient alfalfa cultivars,contributing to effective agricultural strategies for facing future climate change.展开更多
As a powerful tool for target prediction,reverse docking remains largely unexplored.The objective evaluation of reverse docking software can help us know better about the strength and weakness of these tools,hence gui...As a powerful tool for target prediction,reverse docking remains largely unexplored.The objective evaluation of reverse docking software can help us know better about the strength and weakness of these tools,hence guiding us in target prediction.In the present study,we evaluated the target prediction power of Glide(SP)against general inhibitors and selective inhibitors.The results showed that the scoring tendency could be different for each ligand,and overall scoring sampling was necessary for a better understanding of the docking score for a certain protein-ligand pair.Besides,the input conformation of the binding pocket could affect the docking result.Glide(SP)showed a preferable performance on the target prediction of the general inhibitors.However,the accuracy of the target prediction of the selective inhibitors was relatively low,indicating that Glide(SP)might not be capable for this task.The case study about COVID-19 proved that coagulation factor Xa might be a potential target of chloroquine.Therefore,we recommend the further development of reverse docking tools and rectification of inter-target scoring bias.展开更多
Alfalfa(Medicago sativa L.) is an important forage crop worldwide. However, little is known about the effects of breeding status and different geographical populations on alfalfa improvement. Here, we sequenced 220 al...Alfalfa(Medicago sativa L.) is an important forage crop worldwide. However, little is known about the effects of breeding status and different geographical populations on alfalfa improvement. Here, we sequenced 220 alfalfa core germplasms and determined that Chinese alfalfa cultivars form an independent group, as evidenced by comparisons of FSTvalues between different subgroups, suggesting that geographical origin plays an important role in group differentiation. By tracing the influence of geographical regions on the genetic diversity of alfalfa varieties in China, we identified 350 common candidate genetic regions and 548 genes under selection. We also defined 165 loci associated with 24 important traits from genome-wide association studies. Of those, 17 genomic regions closely associated with a given phenotype were under selection, with the underlying haplotypes showing significant differences between subgroups of distinct geographical origins. Based on results from expression analysis and association mapping,we propose that 6-phosphogluconolactonase(MsPGL) and a gene encoding a protein with NHL domains(MsNHL) are critical candidate genes for root growth. In conclusion, our results provide valuable information for alfalfa improvement via molecular breeding.展开更多
Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetra...Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetraploid genome and molecular markers linked to important agronomic traits.We herein reported the de novo assembly of the allele-aware chromosome-level genome of Zhongmu-4,a cultivar widely cultivated in China,and a comprehensive database of genomic variations based on resequencing of 220 germplasms.Approximate 2.74 Gb contigs(N50 of 2.06 Mb),accounting for 88.39%of the estimated genome,were assembled,and 2.56 Gb contigs were anchored to 32 pseudo-chromosomes.A total of 34,922 allelic genes were identified from the allele-aware genome.We observed the expansion of gene families,especially those related to the nitrogen metabolism,and the increase of repetitive elements including transposable elements,which probably resulted in the increase of Zhongmu-4 genome compared with Medicago truncatula.Population structure analysis revealed that the accessions from Asia and South America had relatively lower genetic diversity than those from Europe,suggesting that geography may influence alfalfa genetic divergence during local adaption.Genome-wide association studies identified 101 single nucleotide polymorphisms(SNPs)associated with 27 agronomic traits.Two candidate genes were predicted to be correlated with fall dormancy and salt response.We believe that the alleleaware chromosome-level genome sequence of Zhongmu-4 combined with the resequencing data of the diverse alfalfa germplasms will facilitate genetic research and genomics-assisted breeding in variety improvement of alfalfa.展开更多
Although direct-acting antivirals(DAAs)have notably increased the sustained virological response(SVR)rates in hepatitis C virus(HCV)-infected adolescent patients,the efficacy and safety for young children under 3 year...Although direct-acting antivirals(DAAs)have notably increased the sustained virological response(SVR)rates in hepatitis C virus(HCV)-infected adolescent patients,the efficacy and safety for young children under 3 years old remain unclear.Currently,no guidelines recommend DAA therapy for this situation worldwide.Furthermore,the China National Medical Products Administration has not approved any DAA for treating children below 12 years old.Here,we described the characteristics of two children approximately 2 years old,who were infected by HCV genotype 1b and had significant clinical symptoms.Both received 12 weeks of ledipasvir/sofosbuvir(Case 1:45.00 mg/200 mg per day,weight 17 kg;Case 2:33.75 mg/150 mg per day,weight 12 kg).They achieved SVR at 12 weeks after treatment completion without obvious treatment-related adverse effects.Therefore,the safety and benefits of ledipasvir/sofosbuvir treatment in children under 3 years old seem to be confirmed.Our findings require further evaluation.展开更多
基金The authors thank the reviewers for their valuable comments on this manuscript and gratefully acknowledge the financial support for this study provided by grants from the Collaborative Research Key Project between China and EU(granted by the Ministry of Science and Technology of China,2017YFE0111000)the China Forage and Grass Research System(CARS-34)+1 种基金the Agricultural Science and Technology Innovation Program of CAAS(ASTIP-IAS14)the National Natural Science Foundation of China(31772656).
文摘Alfalfa(Medicago sativa L.)is the most widely grown forage legume crop worldwide.Yield and plant height are important agronomic traits influenced by genetic and environmental factors.The objective of this study was to identify quantitative trait loci(QTL)and molecular markers associated with alfalfa yield and plant height.To understand the genetic basis of these traits,a full-sib F1 population composed of 392 individuals was developed by crossing a low-yielding precocious alfalfa genotype(male parent)with a high-yielding latematuring alfalfa cultivar(female parent).The linkage maps were constructed with 3818 single-nucleotide polymorphism(SNP)markers on 64 linkage groups.QTL for yield and plant height were mapped using phenotypic data for three years.Sixteen QTL associated with yield and plant height were identified on chromosomes 1 to 8.Six QTL explained more than 10%of phenotypic variation,representing major loci controlling yield and plant height.One locus on chromosome 1 controlling yield traits had not been identified in previous studies.Three QTL co-located with other QTL(qyield-1 and qheight-7,qheight-5 and qyield-4,qheight-6,and qyield-6).With further validation,the markers closely linked with these QTL may be used for marker-assisted selection in breeding new alfalfa varieties with high yield.
基金This study was supported by a grant from the Innovation Capability Development Project of Jiangsu Province(No.BM2015004).
文摘Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.
基金supported by the earmarked fund for CARS(CARS-34)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(ASTIP-IAS14)the Science Fund Program for Distinguished Young Scholars of the National Natural Science Foundation of China(Overseas)to Yongfeng Zhou.
文摘Given the escalating impact of climate change on agriculture and food security,gaining insights into the evolutionary dynamics of climatic adaptation and uncovering climate-adapted variation can empower the breeding of climate-resilient crops to face future climate change.Alfalfa(Medicago sativa subsp.sativa),the queen of forages,shows remarkable adaptability across diverse global environments,making it an excellent model for investigating species responses to climate change.In this study,we performed population genomic analyses using genome resequencing data from 702 accessions of 24 Medicago species to unravel alfalfa’s climatic adaptation and genetic susceptibility to future climate change.We found that interspecific genetic exchange has contributed to the gene pool of alfalfa,particularly enriching defense and stress-response genes.Intersubspecific introgression between M.sativa subsp.falcata(subsp.falcata)and alfalfa not only aids alfalfa’s climatic adaptation but also introduces genetic burden.A total of 1671 genes were associated with climatic adaptation,and 5.7%of them were introgressions from subsp.falcata.By integrating climate-associated variants and climate data,we identified populations that are vulnerable to future climate change,particularly in higher latitudes of the Northern Hemisphere.These findings serve as a clarion call for targeted conservation initiatives and breeding efforts.We also identified preadaptive populations that demonstrate heightened resilience to climate fluctuations,illuminating a pathway for future breeding strategies.Collectively,this study enhances our understanding about the local adaptation mechanisms of alfalfa and facilitates the breeding of climate-resilient alfalfa cultivars,contributing to effective agricultural strategies for facing future climate change.
基金National Key Research and Development Project(Grant No.2019YFC1708900)the National Natural Science Foundation of China(Grant No.81872730+6 种基金8167327921772005)National Major Scientific and Technological Special Project for Significant New Drugs Development(Grant No.2018ZX09735001-0032019ZX09201005-0012019ZX09204-001)Beijing Natural Science Foundation(Grant No.72020887172118)。
文摘As a powerful tool for target prediction,reverse docking remains largely unexplored.The objective evaluation of reverse docking software can help us know better about the strength and weakness of these tools,hence guiding us in target prediction.In the present study,we evaluated the target prediction power of Glide(SP)against general inhibitors and selective inhibitors.The results showed that the scoring tendency could be different for each ligand,and overall scoring sampling was necessary for a better understanding of the docking score for a certain protein-ligand pair.Besides,the input conformation of the binding pocket could affect the docking result.Glide(SP)showed a preferable performance on the target prediction of the general inhibitors.However,the accuracy of the target prediction of the selective inhibitors was relatively low,indicating that Glide(SP)might not be capable for this task.The case study about COVID-19 proved that coagulation factor Xa might be a potential target of chloroquine.Therefore,we recommend the further development of reverse docking tools and rectification of inter-target scoring bias.
基金This work was supported by the Collaborative Research Key Project between China and EU(2017YFE0111000)the National Natural Science Foundation of China(31971758,31772656)the Innovation Program of CAAS(ASTIP-IAS14)。
文摘Alfalfa(Medicago sativa L.) is an important forage crop worldwide. However, little is known about the effects of breeding status and different geographical populations on alfalfa improvement. Here, we sequenced 220 alfalfa core germplasms and determined that Chinese alfalfa cultivars form an independent group, as evidenced by comparisons of FSTvalues between different subgroups, suggesting that geographical origin plays an important role in group differentiation. By tracing the influence of geographical regions on the genetic diversity of alfalfa varieties in China, we identified 350 common candidate genetic regions and 548 genes under selection. We also defined 165 loci associated with 24 important traits from genome-wide association studies. Of those, 17 genomic regions closely associated with a given phenotype were under selection, with the underlying haplotypes showing significant differences between subgroups of distinct geographical origins. Based on results from expression analysis and association mapping,we propose that 6-phosphogluconolactonase(MsPGL) and a gene encoding a protein with NHL domains(MsNHL) are critical candidate genes for root growth. In conclusion, our results provide valuable information for alfalfa improvement via molecular breeding.
基金supported by the National Natural Science Foundation of China(Grant Nos.31971758 to QY and 32071865 to RL)the Collaborative Research Key Project between China and EU(Grant No.2017YFE0111000)+2 种基金the China Agriculture Research System of MOF and MARA(Grant No.CARS-34)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(Grant No.ASTIP-IAS14)the Key Projects in Science and Technology of Inner Mongolia,China(Grant No.2021ZD0031)。
文摘Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetraploid genome and molecular markers linked to important agronomic traits.We herein reported the de novo assembly of the allele-aware chromosome-level genome of Zhongmu-4,a cultivar widely cultivated in China,and a comprehensive database of genomic variations based on resequencing of 220 germplasms.Approximate 2.74 Gb contigs(N50 of 2.06 Mb),accounting for 88.39%of the estimated genome,were assembled,and 2.56 Gb contigs were anchored to 32 pseudo-chromosomes.A total of 34,922 allelic genes were identified from the allele-aware genome.We observed the expansion of gene families,especially those related to the nitrogen metabolism,and the increase of repetitive elements including transposable elements,which probably resulted in the increase of Zhongmu-4 genome compared with Medicago truncatula.Population structure analysis revealed that the accessions from Asia and South America had relatively lower genetic diversity than those from Europe,suggesting that geography may influence alfalfa genetic divergence during local adaption.Genome-wide association studies identified 101 single nucleotide polymorphisms(SNPs)associated with 27 agronomic traits.Two candidate genes were predicted to be correlated with fall dormancy and salt response.We believe that the alleleaware chromosome-level genome sequence of Zhongmu-4 combined with the resequencing data of the diverse alfalfa germplasms will facilitate genetic research and genomics-assisted breeding in variety improvement of alfalfa.
基金the Special Project of Guangdong Rural Science and Technology Commissioner of China(KTPYJ2021014)。
文摘Although direct-acting antivirals(DAAs)have notably increased the sustained virological response(SVR)rates in hepatitis C virus(HCV)-infected adolescent patients,the efficacy and safety for young children under 3 years old remain unclear.Currently,no guidelines recommend DAA therapy for this situation worldwide.Furthermore,the China National Medical Products Administration has not approved any DAA for treating children below 12 years old.Here,we described the characteristics of two children approximately 2 years old,who were infected by HCV genotype 1b and had significant clinical symptoms.Both received 12 weeks of ledipasvir/sofosbuvir(Case 1:45.00 mg/200 mg per day,weight 17 kg;Case 2:33.75 mg/150 mg per day,weight 12 kg).They achieved SVR at 12 weeks after treatment completion without obvious treatment-related adverse effects.Therefore,the safety and benefits of ledipasvir/sofosbuvir treatment in children under 3 years old seem to be confirmed.Our findings require further evaluation.
