Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Measuring Dependence Risk of Funds with Copula in China

The aim of this paper is to measure dependence risk of fund market with copulas in China. Firstly, we introduce several common copula functions, then estimate parameters of copula function, and discuss how to select the optimal copula function. Finally, according to Shanghai and Shenzhen fund data, empirical analysis was done. Different combinations of risk values were obtained.

OsWRKY78 regulates panicle exsertion via gibberellin signaling pathway in rice

Panicle exsertion is one of the crucial agronomic traits in rice(Oryza sativa).Shortening of panicle exsertion often leads to panicle enclosure and severely reduces seed production.Gibberellin(GA)plays important roles in regulating panicle exsertion.However,the underlying mechanism and the relative regulatory network remain elusive.Here,we characterized the oswrky78 mutant showing severe panicle enclosure,and found that the defect of oswrky78 is caused by decreased bioactive GA contents.Biochemical analysis demonstrates that OsWRKY78 can directly activate GA biosynthesis and indirectly suppress GA metabolism.Moreover,we found OsWRKY78 can interact with and be phosphorylated by mitogen-activated protein kinase(MAPK)kinase OsMAPK6,and this phosphorylation can enhance OsWRKY78 stability and is necessary for its biological function.Taken together,these results not only reveal the critical function of OsWRKY78,but also reveal its mechanism via mediating crosstalk between MAPK and the GA signaling pathway in regulating panicle exsertion.

OsMKKK70 regulates grain size and leaf angle in rice through the OsMKK4-OsMAPK6-OsWRKY53 signaling pathway

Grain size and leaf angle are key agronomic traits that determine final yields in rice.However,the underlying molecular mechanisms are not well understood.Here we demonstrate that the Oryza sativa Mitogen Activated Protein Kinase Kinase Kinase OsMKKK70 regulates grain size and leaf angle in rice.Overexpressing OsMKKK70 caused plants to produce longer seeds.The osmkkk62/70 double mutant and the osmkkk55/62/70 triple mutant displayed significantly smaller seeds and a more erect leaf angle compared to the wild type,indicating that OsMKKK70 functions redundantly with its homologs Os MKKK62 and Os MKKK55.Biochemical analysis demonstrated that OsMKKK70 is an active kinase and that OsMKKK70 interacts with Os MKK4 and promotes Os MAPK6 phosphorylation.In addition,the osmkkk62/70 double mutant showed reduced sensitivity to Brassinosteroids(BRs).Finally,overexpressing constitutively active Os MKK4,Os MAPK6,and Os WRKY53 can partially complement the smaller seed size,erect leaf,and BR hyposensitivity of the osmkkk62/70 double mutant.Taken together,these findings suggest that OsMKKK70 might regulate grain size and leaf angle in rice by activating Os MAPK6 and that OsMKKK70,Os MKK4,Os MAPK6,and Os WRKY53 function in a common signaling pathway that controls grain shape and leaf angle.

Oryza sativa mediator subunit OsMED25 interacts with OsBZR1 to regulate brassinosteroid signaling and plant architecture in rice

Brassinosteroids(BRs)are plant-specific steroid hormones which regulate plant growth,development,and adaptation.Transcriptional regulation plays key roles in plant hormone signaling.A mediator can serve as a bridge between gene-specific transcription factors and the RNA polymerase machinery,functioning as an essential component in regulating the transcriptional process.However,whether a mediator is involved in BR signaling is unknown.Here,we discovered that Oryza sativa mediator subunit 25(Os MED25)is an important regulator of rice BR signaling.Phenotypic analyses showed that the Os MED25-RNAi and osmed25 mutant presented erect leaves,as observed in BR-deficient mutants.In addition,the Os MED25-RNAi and osmed25 mutant exhibited decreased BR sensitivity.Genetic analysis indicated that Os MED25-RNAi could suppress the enhanced BR signaling phenotype of Osbzr1-D.Further biochemical analysis showed that Os MED25 interacts with Os BZR1 in vivo,and Os MED25 is enriched on the promoter of Os BZR1 target genes.RNA sequencing analysis indicated that Os MED25 affects the expression of approximately 45%of Os BZR1-regulated genes and mainly functions as a corepressor of Os BZR1.Together,these findings revealed that Os MED25 regulates rice BR signaling by interacting with Os BZR1 and modulating the expression of Os BZR1 target genes,thus expanding our understanding of the roles of mediators in plant hormone signaling.

bZIP71 delays flowering by suppressing Ehd1 expression in rice

Flowering time is a fundamental factor determining the global distribution and final yield of rice(Oryza sativa).Although diverse flowering time genes have been reported in this crop,the transcriptional regulation of its key flowering genes are poorly understood.Here,we report that a basic leucine zipper transcription factor,bZIP71,functions as a flowering repressor.The overexpression of bZIP71 delays flowering,while the bzip71 mutant flowers early in both long-day and short-day conditions.A genetic analysis showed that the regulation of flowering by bZIP71 might be independent of Heading date 2(Hd2),Hd4,and Hd5.Importantly,bZIP71 directly associates with the Early heading date 1(Ehd1)promoter and represses its transcription,and genetically the function of bZIP71 is impaired in the ehd1 mutant.Moreover,bZIP71 interacts with major components of polycomb repressive complex 2(PRC2),SET domain group protein 711(SDG711),and Fertilization independent endosperm 2(FIE2),through which bZIP71 regulates the H3K27me3 level of Ehd1.Taken together,we present a transcriptional regulatory mechanism in which bZIP71 enhances the H3K27me3 level of Ehd1 and transcriptionally represses its expression,which not only offers a novel insight into a flowering pathway,but also provides a valuable putative target for the genetic engineering and breeding of elite rice cultivars.