An Arabidopsis mutant of inositol pentakisphosphate 2-kinase AtIPK1 displays reduced arsenate tolerance.

Arsenate [As(V)] toxicity is considered to be derived from similarities in the chemical properties of As(V) and phosphate (Pi). An Arabidopsis thaliana mutant of inositol pentakisphosphate 2-kinase (AtIPK1), atipk1-1, has previously exhibited lower level of phytate and higher level of Pi, relative to wild-type (WT). Here, atipk1-1 displayed hypersensitivity to As(V) stress and less As(V) uptake when compared to WT. Overexpression of AtIPK1 controlled by the CaMV 35S promoter partially rescued the As(V)-sensitive phenotype of atipk1-1. When compared to control Pi status, addition of Pi enhanced As(V) tolerance of both WT and atipk1-1 plants, while the arsenic concentration was less reduced in the latter genotype. Despite the higher Pi level in atipk1-1 than did WT plants, the mutant suffered more severe Pi starvation under Pi limitation stress, indicating that Pi homeostasis was altered in the mutant. Gene expression analysis of WT and atipk1-1 plants showed the diverse effect of As(V) stress on Pi starvation-dependent regulation of Pi-responsive genes. Our study suggested that a particular mechanism of As(V) toxicity existed in atipk1-1 mutant, and may offer new insights into the interactions between Pi homeostasis and As(V) detoxification in plants.

Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study.

Astragalus membranaceus has complex components as a natural drug and has multilevel, multitarget, and multichannel effects on dilated cardiomyopathy (DCM). However, the immune mechanism, gene module, and molecular subtype of astragalus membranaceus in the treatment of DCM are still not revealed. Microarray information of GSE84796 was downloaded from the GEO database, including RNA sequencing data of seven normal cardiac tissues and ten DCM cardiac tissues. A total of 4029 DCM differentially expressed genes were obtained, including 1855 upregulated genes and 2174 downregulated genes. GO/KEGG/GSEA analysis suggested that the activation of T cells and B cells was the primary cause of DCM. WGCNA was used to obtain blue module genes. The blue module genes are primarily ADCY7, BANK1, CD1E, CD19, CD38, CD300LF, CLEC4E, FLT3, GPR18, HCAR3, IRF4, LAMP3, MRC1, SYK, and TLR8, which successfully divided DCM into three molecular subtypes. Based on the CIBERSORT algorithm, the immune infiltration profile of DCM was analyzed. Many immune cell subtypes, including the abovementioned immune cells, showed different levels of increased infiltration in the myocardial tissue of DCM. However, this infiltration pattern was not obviously correlated with clinical characteristics, such as age, EF, and sex. Based on network pharmacology and ClueGO, 20 active components of Astragalus membranaceus and 40 components of DMCTGS were obtained from TCMSP. Through analysis of the immune regulatory network, we found that Astragalus membranaceus effectively regulates the activation of immune cells, such as B cells and T cells, cytokine secretion, and other processes and can intervene in DCM at multiple components, targets, and levels. The above mechanisms were verified by molecular docking results, which confirmed that AKT1, VEGFA, MMP9, and RELA are promising potential targets of DCM.