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Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan–Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis. [ABSTRACT FROM AUTHOR]

Homeodomain-Leucine Zipper (HD-Zip) proteins are important ubiquitous and diverse molecular chaperones in plants. We characterized a gene CaATHB-12 derived from HD-Zip I subfamily which was intensively induced by exogenous abscisic acid (ABA), salt, and mannitol applications in a pepper cultivar. Efficient gene silencing lines were created from pepper, and stable heterologous overexpression lines were created from Arabidopsis to achieve a comprehensive exploration of gene function. The functional study of CaATHB-12 in pepper increased plant sensitivity to ABA stress, while the over-expressing CaATHB-12 in Arabidopsis lines revealed that tolerance to ABA, salt, and mannitol stresses was decreased. Furthermore, CaATHB-12 plays a fundamental role in elevating the tolerance to these stresses through the increased expression of other stress related genes, increasing the activities of antioxidant enzymes and scavenging the reactive oxygen species. The studied functions of the CaATHB-12 gene may provide some insights in exquisite molecular detail by pursuing signal transduction mechanisms that converge on gene expression patterns. [ABSTRACT FROM AUTHOR]

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the relationships between single-nucleotide polymorphisms (SNPs) of crucial molecules in the cGAS-STING signalling pathway and the susceptibility to, induction chemotherapy response of, and prognosis of acute myeloid leukaemia (AML) in Chinese patients. Methods: Thirteen SNPs of crucial molecules in the cGAS-STING signalling pathway were genotyped in 262 AML patients using the Sequenom MassARRAY system. The associations of SNPs with susceptibility, and induction chemotherapy response were analysed using the chi-square test or Fisher's exact test and univariate binary logistic regression, the connection of SNPs with prognosis of AML was analysed using the log-rank test, and Kaplan–Meier curves were applied for survival estimation. Results: In our study, gene polymorphisms of cGAS-STING signalling pathway molecules could be vitally associated with AML. In the recessive model, the cGAS rs311678 gene polymorphism could be closely related to AML susceptibility (CC vs. TT + TC, odds ratio (OR) = 0.480, 95% confidence interval (CI) = 0.260–0.889, p = 0.020). Moreover, IKKA rs3808917 might be associated with the WBC count, cGAS rs311678 could be associated with the bone marrow (BM) blast percentage, and NF-κB rs1056890 under codominant and recessive models could be connected with the HGB level. Patients who were STING rs7380272 TT/CT carriers was likely to have higher insensitivity to induction chemotherapy than CC carriers (TT + CT vs. CC, OR = 2.917, 95% CI = 1.073–7.929, p = 0.036). Survival analysis indicated that the IKKB rs3747811 TT genotype might be associated with decreased overall survival (OS) (p < 0.05). Conclusions: SNPs of molecules in the cGAS-STING signalling pathway could be significantly associated with AML. The cGAS rs311678 gene polymorphism could be associated with AML susceptibility, the STING rs7380272 variant might be related to induction chemotherapy response, and IKKB rs3747811 tended to be associated with AML overall survival. Moreover, IKKA rs3808917 could be associated with the WBC count, cGAS rs311678 could be associated with the BM blast percentage, and NF-κB rs1056890 might be related to the HGB level. [ABSTRACT FROM AUTHOR]

MYB transcription factors play a key role in anthocyanin biosynthesis. However, there are few reports on MYB transcription factors that can regulate anthocyanin biosynthesis in potato. In this study, the StMYB113 gene was isolated from potato and characterized. Transient activation experiments showed that the StMYB113 gene could promote anthocyanin biosynthesis in tobacco leaves by enhancing the expression of genes encoding anthocyanin biosynthesis-related enzymes. In addition, overexpression of the StMYB113 gene promoted anthocyanin accumulation in potato tuber skin. Furthermore, transient luciferase analysis showed that StMYB113 enhanced the promoter activities of StF3H and StDFR genes significantly. These results indicated that the StMYB113 gene could promote anthocyanin accumulation in potato tuber skin by directly activating the expression of StF3H and StDFR. The promoter activity of StMYB113 was significantly higher in light than in dark conditions, suggesting that the expression of StMYB113 is induced by light. These findings illustrate the role and regulation of the StMYB113 gene in potato anthocyanin biosynthesis and enrich the regulatory theory of potato anthocyanin biosynthesis. [ABSTRACT FROM AUTHOR]