The continuous improvement of the cyber threat intelligence sharing mechanism provides new ideas to deal with Advanced Persistent Threats(APT).Extracting attack behaviors,i.e.,Tactics,Techniques,Procedures(TTP)from Cy...The continuous improvement of the cyber threat intelligence sharing mechanism provides new ideas to deal with Advanced Persistent Threats(APT).Extracting attack behaviors,i.e.,Tactics,Techniques,Procedures(TTP)from Cyber Threat Intelligence(CTI)can facilitate APT actors’profiling for an immediate response.However,it is difficult for traditional manual methods to analyze attack behaviors from cyber threat intelligence due to its heterogeneous nature.Based on the Adversarial Tactics,Techniques and Common Knowledge(ATT&CK)of threat behavior description,this paper proposes a threat behavioral knowledge extraction framework that integrates Heterogeneous Text Network(HTN)and Graph Convolutional Network(GCN)to solve this issue.It leverages the hierarchical correlation relationships of attack techniques and tactics in the ATT&CK to construct a text network of heterogeneous cyber threat intelligence.With the help of the Bidirectional EncoderRepresentation fromTransformers(BERT)pretraining model to analyze the contextual semantics of cyber threat intelligence,the task of threat behavior identification is transformed into a text classification task,which automatically extracts attack behavior in CTI,then identifies the malware and advanced threat actors.The experimental results show that F1 achieve 94.86%and 92.15%for the multi-label classification tasks of tactics and techniques.Extend the experiment to verify the method’s effectiveness in identifying the malware and threat actors in APT attacks.The F1 for malware and advanced threat actors identification task reached 98.45%and 99.48%,which are better than the benchmark model in the experiment and achieve state of the art.The model can effectivelymodel threat intelligence text data and acquire knowledge and experience migration by correlating implied features with a priori knowledge to compensate for insufficient sample data and improve the classification performance and recognition ability of threat behavior in text.展开更多
N6-Methyladenosine(m^(6)A)is one of the most abundant modifications of eukaryotic mRNA,but its comprehensive biological functionality remains further exploration.In this study,we identified and characterized a new flo...N6-Methyladenosine(m^(6)A)is one of the most abundant modifications of eukaryotic mRNA,but its comprehensive biological functionality remains further exploration.In this study,we identified and characterized a new flowering-promoting gene,EARLY HEADING DATE6(EHD6),in rice.EHD6 encodes an RNA recognition motif(RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein(RNP)granules and can bind both m^(6)A-modified RNA and unmodified RNA indiscriminately.We found that EHD6 can physically interact with YTH07,a YTH(YT521-B homology)domain-containing m^(6)A reader.We showed that their interaction enhances the binding of an m^(6)A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation.Within these condensates,the mRNA of a rice flowering repressor,CONSTANS-like 4(OsCOL4),becomes sequestered,leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway.Taken together,these results not only shed new light on the molecular mechanism of efficient m^(6)A recognition by the collaboration between an RNA binding protein and YTH family m^(6)A reader,but also uncover the potential for m^(6)A-mediated translation regulation through phaseseparated ribonucleoprotein condensation in rice.展开更多
High chalkiness is a major problem in many rice-producing areas of the world, especially in hybrid rice (Oryza sativa L.) in China. We previously showed a major quantitative trait locus for the percentage of grains ...High chalkiness is a major problem in many rice-producing areas of the world, especially in hybrid rice (Oryza sativa L.) in China. We previously showed a major quantitative trait locus for the percentage of grains with white chalkiness (QTLqPGWC-8) in the interval G1149-R727 on chromosome 8 using a chromosome segment substitution line (CSSL). Here, we selected the line-CSSL50 harboring the QTLqPGWC-8 allele from the CSSLs derived from a cross between Asominori (as a recurrent parent) and IR24 (as a donor parent), which had higher percentage chalkiness, markedly different from that of Asominori. There were also significant differences in starch granules, appearance of amylose content (AAC) and milling qualities between Asominori and CSSL50, but not in grain size or thousand grain weight (TGW). The BC4F2 and BC4F3 populations from a cross between CSSL50 and Asominori were used for fine mapping of qPGWC-8. We narrowed down the location of this QTL to a 142 kb region between Indel markers 8G-7 and 8G-9. QTLqPGWC-8 accounted for 50.9% of the difference in PGWC between the parents. The markers tightly linked to qPGWC-8 should facilitate cloning of the gene underlying this QTL and will be of value for marker-assisted selection in breeding rice varieties with better grain quality.展开更多
Grain size is a key agronomic trait that determines the yield in plants.Regulation of grain size by brassinosteroids(BRs)in rice has been widely reported.However,the relationship between the BR signaling pathway and g...Grain size is a key agronomic trait that determines the yield in plants.Regulation of grain size by brassinosteroids(BRs)in rice has been widely reported.However,the relationship between the BR signaling pathway and grain size still requires further study.Here,we isolated a rice mutant,named small grain2(sg2),which displayed smaller grain and a semi-dwarf phenotype.The decreased grain size was caused by repressed cell expansion in spikelet hulls of the sg2 mutant.Using map-based cloning combined with a Mut Map approach,we cloned SG2,which encodes a plant-specific protein with a ribonuclease H-like domain.SG2 is a positive regulator downstream of GLYCOGEN SYNTHASE KINASE2(GSK2)in response to BR signaling,and its mutation causes insensitivity to exogenous BR treatment.Genetical and biochemical analysis showed that GSK2 interacts with and phosphorylates SG2.We further found that BRs enhance the accumulation of SG2 in the nucleus,and subcellular distribution of SG2 is regulated by GSK2 kinase activity.In addition,Oryza sativa OVATE family protein 19(OsOFP19),a negative regulator of grain shape,interacts with SG2 and plays an antagonistic role with SG2 in controlling gene expression and grain size.Our results indicated that SG2 is a new component of GSK2-related BR signaling response and regulates grain size by interacting with Os OFP19.展开更多
Pentatricopeptide repeat(PPR) proteins function in post-transcriptional regulation of organellar gene expression. Although several PPR proteins are known to function in chloroplast development in rice(Oryza sativa), t...Pentatricopeptide repeat(PPR) proteins function in post-transcriptional regulation of organellar gene expression. Although several PPR proteins are known to function in chloroplast development in rice(Oryza sativa), the detailed molecular functions of many PPR proteins remain unclear.Here, we characterized a rice young leaf white stripe(ylws) mutant, which has defective chloroplast development during early seedling growth.Map-based cloning revealed that YLWS encodes a novel P-type chloroplast-targeted PPR protein with 11 PPR motifs. Further expression analyses showed that many nuclear-and plastid-encoded genes in the ylws mutant were significantly changed at the RNA and protein levels. The ylws mutant was impaired in chloroplast ribosome biogenesis and chloroplast development under low-temperature conditions. The ylws mutation causes defects in the splicing of atpF, ndhA, rpl2,and rps12, and editing of ndhA, ndhB, and rps14transcripts. YLWS directly binds to specific sites in the atpF, ndhA, and rpl2 pre-mRNAs. Our results suggest that YLWS participates in chloroplast RNA group II intron splicing and plays an important role in chloroplast development during early leaf development.展开更多
Lipid homeostasis is considered to be related to intestinal metabolic balance,while its role in the pathogenesis and treatment of ulcerative colitis(UC)remains largely unexplored.The present study aimed to identify th...Lipid homeostasis is considered to be related to intestinal metabolic balance,while its role in the pathogenesis and treatment of ulcerative colitis(UC)remains largely unexplored.The present study aimed to identify the target lipids related to the occurrence,development and treatment of UC by comparing the lipidomics of UC patients,mice and colonic organoids with the corresponding healthy controls.Here,multi-dimensional lipidomics based on LC–QTOF/MS,LC–MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles.The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis,in which triglycerides and phosphatidylcholines were significantly reduced.Notably,phosphatidylcholine 34:1(PC34:1)was characterized by high abundance and closely correlation with UC disease.Our results also revealed that down-regulation of PC synthase PCYT1 α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1,and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate,thus exerting an anti-UC effect.Collectively,our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals,but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.展开更多
Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with chloroplast developmental status and is essential for the photoautotrophic lifestyle of plants.Previous studies have established that te...Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with chloroplast developmental status and is essential for the photoautotrophic lifestyle of plants.Previous studies have established that tetrapyrrole biosynthesis(TPB)and plastid gene expression(PGE)play essential roles in plastid retrograde signaling during early chloroplast biogenesis;however,their functional relationship remains unknown.In this study,we generated a series of rice TPB-related gun(genome uncoupled)mutants and systematically analyzed their effects on nuclear and plastid gene expression under normal conditions or when subjected to treatments with norflurazon(NF;a noncompetitive inhibitor of carotenoid biosynthesis)and/or lincomycin(Lin;a specific inhibitor of plastid translation).We show that under NF treatment,expression of plastid-encoded polymerase(PEP)-transcribed genes is significantly reduced in the wild type but is derepressed in the TPB-related gun mutants.We further demonstrate that the derepressed expression of PEPtranscribed genes may be caused by increased expression of the PEP core subunit and nuclear-encoded sigma factors and by elevated copy numbers of plastid genome per haploid genome.In addition,we show that expression of photosynthesis-associated nuclear genes(PhANGs)and PEP-transcribed genes is correlated in the rice TPB-related gun mutants,with or without NF or Lin treatment.A similar correlation between PhANGs and PGE is also observed in the Arabidopsis gun4 and gun5 mutants.Moreover,we show that increased expression of PEP-transcribed plastid genes is necessary for the gun phenotype in NF-treated TPB-related gun mutants.Further,we provide evidence that these TPB-related GUN genes act upstream of GUN1 in the regulation of retrograde signaling.Taken together,our results suggest that the TPB-related GUN genes control retrograde plastid signaling by regulating the PGE-dependent retrograde signaling pathway.展开更多
The size of the top three leaves of rice plants is strongly associated with yield; thus, it is important to consider quantitative traits representing leaf size (e.g., length and width) when breeding novel rice varie...The size of the top three leaves of rice plants is strongly associated with yield; thus, it is important to consider quantitative traits representing leaf size (e.g., length and width) when breeding novel rice varieties. It is challenging to measure such traits on a large scale in the field, and little is known about the genetic factors that determine the size of the top three leaves. In the present study, a population of recombinant inbred lines (RILs) and reciprocal single chromosomal segment substitution lines (SSSLs) derived from the progeny of a japonica Asominori x indica IR24 cross were grown under four diverse environmental conditions. Six morphological traits associated with leaf size were measured,namely length and width of the flag, second and third leaves. In the RIL population, 49 QTLs were identified that clustered in 30 genomic region. Twenty-three of these QTLs were confirmed in the SSSL population. A comparison with previously reported genes/QTLs revealed eight novel genomic regions that contained uncharacterized ORFs associated with leaf size. The QTLs identified in this study can be used for marker- assisted breeding and for fine mapping of novel genetic elements controlling leaf size in rice.展开更多
基金supported by China’s National Key R&D Program,No.2019QY1404the National Natural Science Foundation of China,Grant No.U20A20161,U1836103the Basic Strengthening Program Project,No.2019-JCJQ-ZD-113.
文摘The continuous improvement of the cyber threat intelligence sharing mechanism provides new ideas to deal with Advanced Persistent Threats(APT).Extracting attack behaviors,i.e.,Tactics,Techniques,Procedures(TTP)from Cyber Threat Intelligence(CTI)can facilitate APT actors’profiling for an immediate response.However,it is difficult for traditional manual methods to analyze attack behaviors from cyber threat intelligence due to its heterogeneous nature.Based on the Adversarial Tactics,Techniques and Common Knowledge(ATT&CK)of threat behavior description,this paper proposes a threat behavioral knowledge extraction framework that integrates Heterogeneous Text Network(HTN)and Graph Convolutional Network(GCN)to solve this issue.It leverages the hierarchical correlation relationships of attack techniques and tactics in the ATT&CK to construct a text network of heterogeneous cyber threat intelligence.With the help of the Bidirectional EncoderRepresentation fromTransformers(BERT)pretraining model to analyze the contextual semantics of cyber threat intelligence,the task of threat behavior identification is transformed into a text classification task,which automatically extracts attack behavior in CTI,then identifies the malware and advanced threat actors.The experimental results show that F1 achieve 94.86%and 92.15%for the multi-label classification tasks of tactics and techniques.Extend the experiment to verify the method’s effectiveness in identifying the malware and threat actors in APT attacks.The F1 for malware and advanced threat actors identification task reached 98.45%and 99.48%,which are better than the benchmark model in the experiment and achieve state of the art.The model can effectivelymodel threat intelligence text data and acquire knowledge and experience migration by correlating implied features with a priori knowledge to compensate for insufficient sample data and improve the classification performance and recognition ability of threat behavior in text.
基金supported by the Key Laboratory of Biology,Genetics and Breeding of Japonica Rice in Mid-lower Yangtze River,Ministry of Agriculture and Rural Affairs,China,and the Jiangsu Collaborative Innovation Center for Modern Crop Production,China.Funding for this work was provided by the National Key Research and Development Program of China(2020YFE0202300 and 2021YFD1200504)the National Natural Science Foundation of China(31971910 and 32272115)+1 种基金the National Science Foundation of Jiangsu Province(BK20212010 and BK20230038)the Foundation of Biological Breeding Zhongshan Lab(BM2022008-03,ZSBBL-KY2023-04,and ZSBBL-KY2023-06).
文摘N6-Methyladenosine(m^(6)A)is one of the most abundant modifications of eukaryotic mRNA,but its comprehensive biological functionality remains further exploration.In this study,we identified and characterized a new flowering-promoting gene,EARLY HEADING DATE6(EHD6),in rice.EHD6 encodes an RNA recognition motif(RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein(RNP)granules and can bind both m^(6)A-modified RNA and unmodified RNA indiscriminately.We found that EHD6 can physically interact with YTH07,a YTH(YT521-B homology)domain-containing m^(6)A reader.We showed that their interaction enhances the binding of an m^(6)A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation.Within these condensates,the mRNA of a rice flowering repressor,CONSTANS-like 4(OsCOL4),becomes sequestered,leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway.Taken together,these results not only shed new light on the molecular mechanism of efficient m^(6)A recognition by the collaboration between an RNA binding protein and YTH family m^(6)A reader,but also uncover the potential for m^(6)A-mediated translation regulation through phaseseparated ribonucleoprotein condensation in rice.
基金supported by the National Natural Science Foundation of China(30771325)National Key Transform Program(2008ZX08001-06)+2 种基金the earmarked fund for Modern Agro-industry Technology Research SystemJiangsu Cultivar Development Program(BE2008354 and BE2009301-3)the 111 project
文摘High chalkiness is a major problem in many rice-producing areas of the world, especially in hybrid rice (Oryza sativa L.) in China. We previously showed a major quantitative trait locus for the percentage of grains with white chalkiness (QTLqPGWC-8) in the interval G1149-R727 on chromosome 8 using a chromosome segment substitution line (CSSL). Here, we selected the line-CSSL50 harboring the QTLqPGWC-8 allele from the CSSLs derived from a cross between Asominori (as a recurrent parent) and IR24 (as a donor parent), which had higher percentage chalkiness, markedly different from that of Asominori. There were also significant differences in starch granules, appearance of amylose content (AAC) and milling qualities between Asominori and CSSL50, but not in grain size or thousand grain weight (TGW). The BC4F2 and BC4F3 populations from a cross between CSSL50 and Asominori were used for fine mapping of qPGWC-8. We narrowed down the location of this QTL to a 142 kb region between Indel markers 8G-7 and 8G-9. QTLqPGWC-8 accounted for 50.9% of the difference in PGWC between the parents. The markers tightly linked to qPGWC-8 should facilitate cloning of the gene underlying this QTL and will be of value for marker-assisted selection in breeding rice varieties with better grain quality.
基金supported by the Key Laboratory of Biology,Genetics and Breeding of Japonica Rice in Mid-lower Yangtze River,Ministry of Agriculture of China,Jiangsu Collaborative Innovation Center for Modern Crop Production,Jiangsu Plant Gene Engineering Research Center and the grants from the National Natural Science Foundation of China(32172024)Jiangsu Agricultural Science and Technology Innovation Fund(CX19(1002))Natural Science Foundation of Jiangsu Province,Major Project(BK20212010)。
文摘Grain size is a key agronomic trait that determines the yield in plants.Regulation of grain size by brassinosteroids(BRs)in rice has been widely reported.However,the relationship between the BR signaling pathway and grain size still requires further study.Here,we isolated a rice mutant,named small grain2(sg2),which displayed smaller grain and a semi-dwarf phenotype.The decreased grain size was caused by repressed cell expansion in spikelet hulls of the sg2 mutant.Using map-based cloning combined with a Mut Map approach,we cloned SG2,which encodes a plant-specific protein with a ribonuclease H-like domain.SG2 is a positive regulator downstream of GLYCOGEN SYNTHASE KINASE2(GSK2)in response to BR signaling,and its mutation causes insensitivity to exogenous BR treatment.Genetical and biochemical analysis showed that GSK2 interacts with and phosphorylates SG2.We further found that BRs enhance the accumulation of SG2 in the nucleus,and subcellular distribution of SG2 is regulated by GSK2 kinase activity.In addition,Oryza sativa OVATE family protein 19(OsOFP19),a negative regulator of grain shape,interacts with SG2 and plays an antagonistic role with SG2 in controlling gene expression and grain size.Our results indicated that SG2 is a new component of GSK2-related BR signaling response and regulates grain size by interacting with Os OFP19.
基金supported by the Key Laboratory of Biology, GeneticsBreeding of Japonica Rice in the Mid-lower Yangtze River, Ministry of Agriculture, China+5 种基金Jiangsu Plant Gene Engineering Research CenterJiangsu Collaborative Innovation Center for Modern Crop ProductionThis research was also supported by grants from the National Natural Science Foundation (92035301)Jiangsu Science and Technology Development Program (BE2021360)Jiangsu Agricultural Science and Technology Innovation Fund Project (SCX (19)1079)the Fundamental Research Funds for the Central Universities (JCQY201902)。
文摘Pentatricopeptide repeat(PPR) proteins function in post-transcriptional regulation of organellar gene expression. Although several PPR proteins are known to function in chloroplast development in rice(Oryza sativa), the detailed molecular functions of many PPR proteins remain unclear.Here, we characterized a rice young leaf white stripe(ylws) mutant, which has defective chloroplast development during early seedling growth.Map-based cloning revealed that YLWS encodes a novel P-type chloroplast-targeted PPR protein with 11 PPR motifs. Further expression analyses showed that many nuclear-and plastid-encoded genes in the ylws mutant were significantly changed at the RNA and protein levels. The ylws mutant was impaired in chloroplast ribosome biogenesis and chloroplast development under low-temperature conditions. The ylws mutation causes defects in the splicing of atpF, ndhA, rpl2,and rps12, and editing of ndhA, ndhB, and rps14transcripts. YLWS directly binds to specific sites in the atpF, ndhA, and rpl2 pre-mRNAs. Our results suggest that YLWS participates in chloroplast RNA group II intron splicing and plays an important role in chloroplast development during early leaf development.
基金supported by the Jiangsu Natural Science Funds(BK20211224,China)the Natural Science Foundation of Hebei Province(Nos.H2021302001,H2020208022,H2020208025,C2021418001,H2021208006,China)the CAMS Innovation Fund for Medical Sciences(2021-I2M-5-011,China).
文摘Lipid homeostasis is considered to be related to intestinal metabolic balance,while its role in the pathogenesis and treatment of ulcerative colitis(UC)remains largely unexplored.The present study aimed to identify the target lipids related to the occurrence,development and treatment of UC by comparing the lipidomics of UC patients,mice and colonic organoids with the corresponding healthy controls.Here,multi-dimensional lipidomics based on LC–QTOF/MS,LC–MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles.The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis,in which triglycerides and phosphatidylcholines were significantly reduced.Notably,phosphatidylcholine 34:1(PC34:1)was characterized by high abundance and closely correlation with UC disease.Our results also revealed that down-regulation of PC synthase PCYT1 α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1,and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate,thus exerting an anti-UC effect.Collectively,our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals,but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.
基金supported by grants from the National Natural Science Foundation of China(91935301)National Natural Science Foundation of China Joint Program(U1701232)+4 种基金Jiangsu Science and Technology Development Program(BE2021360)Jiangsu Agricultural Science and Technology Innovation Fund Project(SCX(19)1079)Jiangsu Province Agriculture Independent Innovation Fund Project(CX(19)1002)National Key Research and Development Program of China(2016YFD0100903)the Fundamental Research Funds for the Central Universities(JCQY201902).
文摘Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with chloroplast developmental status and is essential for the photoautotrophic lifestyle of plants.Previous studies have established that tetrapyrrole biosynthesis(TPB)and plastid gene expression(PGE)play essential roles in plastid retrograde signaling during early chloroplast biogenesis;however,their functional relationship remains unknown.In this study,we generated a series of rice TPB-related gun(genome uncoupled)mutants and systematically analyzed their effects on nuclear and plastid gene expression under normal conditions or when subjected to treatments with norflurazon(NF;a noncompetitive inhibitor of carotenoid biosynthesis)and/or lincomycin(Lin;a specific inhibitor of plastid translation).We show that under NF treatment,expression of plastid-encoded polymerase(PEP)-transcribed genes is significantly reduced in the wild type but is derepressed in the TPB-related gun mutants.We further demonstrate that the derepressed expression of PEPtranscribed genes may be caused by increased expression of the PEP core subunit and nuclear-encoded sigma factors and by elevated copy numbers of plastid genome per haploid genome.In addition,we show that expression of photosynthesis-associated nuclear genes(PhANGs)and PEP-transcribed genes is correlated in the rice TPB-related gun mutants,with or without NF or Lin treatment.A similar correlation between PhANGs and PGE is also observed in the Arabidopsis gun4 and gun5 mutants.Moreover,we show that increased expression of PEP-transcribed plastid genes is necessary for the gun phenotype in NF-treated TPB-related gun mutants.Further,we provide evidence that these TPB-related GUN genes act upstream of GUN1 in the regulation of retrograde signaling.Taken together,our results suggest that the TPB-related GUN genes control retrograde plastid signaling by regulating the PGE-dependent retrograde signaling pathway.
基金supported by the National Natural Science Foundation of China(31471174,and 31271798)
文摘The size of the top three leaves of rice plants is strongly associated with yield; thus, it is important to consider quantitative traits representing leaf size (e.g., length and width) when breeding novel rice varieties. It is challenging to measure such traits on a large scale in the field, and little is known about the genetic factors that determine the size of the top three leaves. In the present study, a population of recombinant inbred lines (RILs) and reciprocal single chromosomal segment substitution lines (SSSLs) derived from the progeny of a japonica Asominori x indica IR24 cross were grown under four diverse environmental conditions. Six morphological traits associated with leaf size were measured,namely length and width of the flag, second and third leaves. In the RIL population, 49 QTLs were identified that clustered in 30 genomic region. Twenty-three of these QTLs were confirmed in the SSSL population. A comparison with previously reported genes/QTLs revealed eight novel genomic regions that contained uncharacterized ORFs associated with leaf size. The QTLs identified in this study can be used for marker- assisted breeding and for fine mapping of novel genetic elements controlling leaf size in rice.