In recent years, increasing evidence has confirmed that exosomal circular RNAs (circRNAs) serve a crucial role in the prognostic prediction and diagnosis of liver cancer (LC). The present study compared the expression patterns of exosomal circRNAs during transarterial chemoembolization (TACE). CircRNA sequencing analysis identified 390 differentially expressed circRNAs between the prior TACE and following the first TACE operation groups and 489 differentially expressed circRNAs between the prior to TACE and following the second TACE operation groups. Gene Ontology analysis of the differentially expressed circRNAs demonstrated that they were associated with fatty acid metabolism, receptor binding and membrane protein complexes. Kyoto Encyclopedia of Genes and Genomes pathway analysis predicted that protein digestion and absorption pathways were activated following TACE. A novel gene was screened out; hsa-circRNA-G004213 (circ-G004213) was significantly upregulated following TACE (fold change >10, P<0.01). Further analysis found circ-G004213 significantly increased the cisplatin sensitivity of HepG2 cells and positively associated with the prognosis of tumor-bearing mice. Based on the potential downstream miRNAs and mRNAs, the circRNA-miRNA-mRNA network was constructed. It was demonstrated that circ-G004213 regulated cisplatin resistance via the miR-513b-5p/PRPF39 axis. Finally, the present study confirmed that circ-G004213 was positively associated with the prognosis of patients with LC following TACE. Therefore, circ-G004213 may be used as an indicator for predicting the efficacy of TACE.

Salt stress is the main abiotic factor affecting alfalfa yield and quality. However, knowledge of the genetic basis of the salt stress response in alfalfa is still limited. Here, a genome-wide association study (GWAS) involving 875,023 single-nucleotide polymorphisms (SNPs) was conducted on 220 alfalfa varieties under both normal and salt-stress conditions. Phenotypic analysis showed that breeding status and geographical origin play important roles in the alfalfa salt stress response. For germination ability under salt stress, a total of 15 significant SNPs explaining 9%–14% of the phenotypic variation were identified. For tolerance to salt stress in the seedling stage, a total of 18 significant SNPs explaining 12%–23% of the phenotypic variation were identified. Transcriptome analysis revealed 2,097 and 812 differentially expressed genes (DEGs) that were upregulated and 2,445 and 928 DEGs that were downregulated in the leaves and roots, respectively, under salt stress. Among these DEGs, many encoding transcription factors (TFs) were found, including MYB-, CBF-, NAC-, and bZIP-encoding genes. Combining the results of our GWAS analysis and transcriptome analysis, we identified a total of eight candidate genes (five candidate genes for tolerance to salt stress and three candidate genes for germination ability under salt stress). Two SNPs located within the upstream region of MsAUX28, which encodes an auxin response protein, were significantly associated with tolerance to salt stress. The two significant SNPs within the upstream region of MsAUX28 existed as three different haplotypes in this panel. Hap 1 (G/G, A/A) was under selection in the alfalfa domestication and improvement process.

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Phosphorus (P) is an indispensable mineral nutrient for plant growth and agricultural production. Plants acquire and redistribute inorganic phosphate (Pi) via Pi transporters (PHT1s/PTs). However, apart from MtPT4, functions of the M. truncatula (Medicago truncatula) PHT1s remain unclear. In this study, we evaluated the function of the PHT1 family transporter MtPT5 in M. truncatula. MtPT5 was closely related to AtPHT1; 1 in Arabidopsis (Arabidopsis thaliana) and GmPT7 in soybean (Glycine max). MtPT5 was highly expressed in leaves in addition to roots and nodules. Ectopic expression of MtPT5 complemented the Pi-uptake deficiency of Arabidopsis pht1;1Δ4Δ double mutant, demonstrating the Pi-transport activity of MtPT5 in plants. When overexpressing MtPT5 in M. truncatula, the transgenic plants showed larger leaves, accompanying with higher biomass and Pi enrichment compared with wild type. All these data demonstrate that MtPT5 is important for leaf growth and Pi accumulation of M. truncatula and provides a target for molecular breeding to improve forage productivity.

mascRNA is a highly conserved tRNA-like noncoding RNA whose function remains largely unknown.We show here that this small RNA molecule played a role in the stringent control of Toll-like receptor (TLR)-mediated innate immune responses. mascRNA inhibited activation of NF-κB and mitogenactivated protein kinase (MAPK) signaling and the production of inflammatory cytokines in macrophages stimulated with lipopolysaccharide (LPS), a TLR4 ligand. Furthermore, exogenous mascRNA alleviated LPS-induced lung inflammation. On the contrary, mascRNA potentiated the phosphorylation of IRF3 and STAT1 and the transcription of interferon-related genes in response to the TLR3 ligand poly(I:C) both in vitro and in vivo. Mechanistically, mascRNA was found to enhance K48-linked ubiquitination and proteasomal degradation of TRAF6, thereby negatively regulating TLRmediated MyD88-dependent proinflammatory signaling while positively regulating TRIF-dependent interferon signaling. Additionally, hnRNP H and hnRNP F were found to interact with mascRNA, promote its degradation, and contribute to the fine-tuning of TLR-triggered immune responses. Taken together, our data identify a dual role of mascRNA in both negative and positive regulation of innate immune responses. Brief summarymascRNA, which is capable of interacting with hnRNP H/F, negatively regulates TLR-mediated proinflammatory response while positively regulates interferon response by promoting degradative ubiquitination of TRAF6.