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Background: Osteosarcoma (OS) is a common malignant bone tumor. Circular RNAs (circRNAs) exert important roles in the pathogenesis of human cancers, including OS. In this study, the authors focused on the role and mechanism of circRNA signal-induced proliferation-associated 1 like 1 (circ_SIPA1L1) in OS. Methods: The enrichment of SIPA1L1, circ_SIPA1L1, microRNA-379-5p (miR-379-5p), and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The colony formation capacity was assessed through colony formation assay. Transwell assays were used to detect the migration and invasion abilities. Western blot assay was used to measure the expression of metastasis-related proteins and MAP3K9. The target interactions between the genes in circ_SIPA1L1/miR-379-5p/MAP3K9 axis were predicted by StarBase and confirmed by dual-luciferase reporter assay. The in vivo role of circ_SIPA1L1 was verified by murine xenograft assay. Results: Circ_SIPA1L1 abundance was aberrantly elevated in OS tissues and cell lines. Circ_SIPA1L1 accelerated the proliferation and metastasis abilities of OS cells. Circ_SIPA1L1 promoted the malignant behaviors of OS cells through elevating MAP3K9 level. MiR-379-5p directly bound to circ_SIPA1L1 and MAP3K9. MiR-379-5p interference rescued the abilities of proliferation and metastasis in OS cells, which were suppressed by the silencing of circ_SIPA1L1. Circ_SIPA1L1 promoted the development of OS via miR-379-5p/MAP3K9 in vivo. Conclusion: Circ_SIPA1L1 promoted the progression of OS via miR-379-5p/MAP3K9 axis. [ABSTRACT FROM AUTHOR]

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging-and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD. [ABSTRACT FROM AUTHOR]

BACKGROUND: The molecular mechanism of sepsis-associated acute kidney injury (SA-AKI) is unclear. We analyzed co-differentially expressed genes (co-DEGs) to elucidate the underlying mechanism and intervention targets of SA-AKI. METHODS: The microarray datasets GSE65682, GSE30718, and GSE174220 were downloaded from the Gene Expression Omnibus (GEO) database. We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes. We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes. We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors. Finally, we conducted a correlation analysis to evaluate the role of the hub genes. RESULTS: Interleukin 32 (IL32) was identified as the hub gene in SA-AKI, and the main enriched signaling pathways were associated with hemopoiesis, cellular response to cytokine stimulus, inflammatory response, and regulation of kidney development. Additionally, IL32 was significantly associated with mortality in SA-AKI patients. Monocytes, macrophages, T cells, and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients. IL32 expression increased significantly in the kidney of septic mouse. Toll-like receptor 2 (TLR2) was significantly and negatively correlated with IL32. CONCLUSION: IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis. TLR2 and relevant immune cells are closely related to key genes. [ABSTRACT FROM AUTHOR]

• HuHMA gene family exhibited unique expression patterns in the growth and development of pitaya. • Transcriptome analysis revealed that HMA-1/11//18/19/28/29 genes exhibited significantly higher expression in single and combined multifactorial stresses. • Comprehensive genome-wide characterization and expression profiling revealed the diverse role of HMA gene members under abiotic stresses and melatonin-mediated tolerance in pitaya. • Exogenous application of melatonin mitigates the effect of combined stresses and HMA gene family members exhibited significantly higher expression. Plants have evolved various ways to improve their tolerance against heavy metal stress including physiological, biochemical, and molecular pathways. The heavy metal-associated (HMA) gene family plays an important role in the detoxification of metal ions. Research on HMA protein diversification, expression, and function in S. undatus is limited. In this study, we have identified 29 HMA proteins andrenamed them as HuHMA-1 to HuHMA-29. Our genome-wide characterization analysis supports the classification of HuHMA gene family members into 11 subfamilies based on their phylogenetic tree topology and conserved motif domains. RNA-Seq analysis exhibited varied expression in pitaya tissues at different developmental stages where we found HuHMA-1 & 16 gene family members strongly expressed in flower buds, flower, pericarp and pulp. Duplication event and Ka/Ks ratio depict that most of the HuHMA genes are generated by segmental duplication, except two pairs of the genes (HuHMA18-HuHMA20 and HuHMA28-HuHMA29) originated through proximal duplication mapped on Chr07 and Chr11. Transcriptome analysis of single and multifactorial stress-treated plants revealed candidate genes (HMA-1/11/18/19/28/29) that might play diverse functions to ameliorate the impact of heavy metal stresses individually and the combined effect of heat and drought. These HMA gene family members exhibited significantly higher expression under multifactorial stresses. The present analysis provides a theoretical foundation for the functional study through advanced biotechnological tools and provides novel insight into the structure and evolution of the HuHMA genes. [ABSTRACT FROM AUTHOR]

Simple Summary: The GRAS gene family plays a critical role in regulation of growth, defense, light and hormone responses. We identified 45 GRAS genes in the pitaya genome and categorized them into nine respective subfamilies: PAT1, SHR, LISCL, HAM, SCR, RGL, LAS, DELLA and SCL-3. Among these 45 HuGRAS family members, we reported nine candidate genes that played key roles in the growth and development of the pitaya plant. The GRAS gene family is one of the most important families of transcriptional factors that have diverse functions in plant growth and developmental processes including axillary meristem patterning, signal-transduction, cell maintenance, phytohormone and light signaling. Despite their importance, the function of GRAS genes in pitaya fruit (Selenicereus undatus L.) remains unknown. Here, 45 members of the HuGRAS gene family were identified in the pitaya genome, which was distributed on 11 chromosomes. All 45 members of HuGRAS were grouped into nine subfamilies using phylogenetic analysis with six other species: maize, rice, soybeans, tomatoes, Medicago truncatula and Arabidopsis. Among the 45 genes, 12 genes were selected from RNA-Seq data due to their higher expression in different plant tissues of pitaya. In order to verify the RNA-Seq data, these 12 HuGRAS genes were subjected for qRT-PCR validation. Nine HuGRAS genes exhibited higher relative expression in different tissues of the plant. These nine genes which were categorized into six subfamilies inlcuding DELLA (HuGRAS-1), SCL-3 (HuGRAS-7), PAT1 (HuGRAS-34, HuGRAS-35, HuGRAS-41), HAM (HuGRAS-37), SCR (HuGRAS-12) and LISCL (HuGRAS-18, HuGRAS-25) might regulate growth and development in the pitaya plant. The results of the present study provide valuable information to improve tropical pitaya through a molecular and conventional breeding program. [ABSTRACT FROM AUTHOR]

• Abiotic stresses (vanadium, drought and heat) adversely affect the growth and production of pitaya. • Genome-wide analysis identified 65 APX genes in the pitaya and were clustered into 13 subfamilies. • Exogenous application of melatonin mitigates the effect of multifactorial stresses. • Melatonin enhanced the expression levels of HuAPX genes, involved in ROS scavenging activities and stress tolerance. Pitaya (Selenicereus undatus L.), an important tropical plant belonging to the Cactaceae family, is rich in antioxidants, dietary fibers and low in calories. Pitaya shows higher tolerance against abiotic stresses; however, various environmental factors lead to excessive production of reactive oxygen species (ROS) persistently that cause injury to the cells. Under vanadium, drought, and heat conditions, plant cells regulate the expression of ascorbate peroxidase (APX , a vital antioxidant enzyme) genes, which play a significant role in detoxifying ROS by catalyzing hydrogen peroxide. In this study, we have identified 65 APX genes (HuAPX) in the pitaya genome and clustered them into 13 subfamilies. Gene structure and motif analysis revealed that HuAPX genes contained well-preserved intron-exon structure and their motif domains also shared the same order within one cluster. Phytohormones-related cis -acting elements including abscisic acid, gibberellin, jasmonic acid, salicylic acid, and auxin were found in abundance in the promoter regions of the HuAPX genes. RNA-seq-based expression analysis of the HuAPX genes unveiled that few genes showed significantly higher expression under single and multifactorial stress combinations of drought, heat, and vanadium. Exogenous applications of melatonin attenuate the vanadium, heat, and drought effects, thus enhancing the growth and development of the pitaya plant, by inducing the HuAPX gene expression efficiently. Moreover, the expression pattern of HuAPX genes were validated through qRT-PCR analysis. Our findings suggest that three candidate genes (HuAPX1/3/6) may play a key role against abiotic stresses by encoding key enzymes related to glutathione metabolism and phenylpropanoid biosynthesis. These results provide valuable information for organizing a new strategy to design the climate-smart pitaya genotypes through conventional and modern biotechnological tools. [ABSTRACT FROM AUTHOR]