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The regulation of plant gene expression by nitrate is a complex regulatory process. Here, we identified 90 GARP family genes in apples by genome-wide analysis. As a member of the GARP gene family, the expression of MdHHO3 (Malus domestica HYPERSENSITIVITY TO LOW PHOSPHATE-ELICITED PRIMARY ROOT SHORTENING1 HOMOLOG 3) is upregulated under N (nitrogen) supply. The results of DNA-binding site analysis and electrophoretic mobility shift assays (EMSA) showed that MdHHO3 binds to the motif-containing GAATC. Furthermore, MdHHO3 binds to its promoter sequence and inhibits its activity. In addition, the overexpression of MdHHO3 in apple calli resulted in less accumulation of nitrate in 35S:MdHHO3-GFP calli and downregulated the expression of the nitrate transport-related genes but upregulated the expression of the nitrate assimilation-related genes. Similarly, the expression of the nitrate transport-related genes was downregulated and the expression of the nitrate assimilation-related genes was upregulated in MdHHO3 overexpression Arabidopsis and tobacco plants. Interaction experiments showed that MdHHO3 could bind to the promoter MdNRT2.1 (NITRATE TRANSPORTER 2.1) and negatively regulate its expression. Moreover, the exposure of MdHHO3-overexpressing Arabidopsis and tobacco to nitrate deficiency resulted in an early senescence phenotype as compared to the WT plants. These results show that MdHHO3 can not only negatively regulate nitrate accumulation in response to nitrate but also promote early leaf senescence under nitrate deficiency. This information may be useful to further reveal the mechanism of the nitrate response and demonstrates that nitrate deficiency induces leaf senescence in apples.

Activation of the NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome plays a key role in host immune response, which is the first line of defense against cellular stresses and pathogen infections. However, excessive inflammasome activation damages host cells, and therefore it must be precisely controlled. Here, we discover that Cullin1 (CUL1), a key component of the Skp1-Cullin1-F-box E3 ligase, plays a critical role in controlling the NLRP3 inflammasome. CUL1 represses inflammasome assembly in cultured cells, suppresses NLRP3 function in human monocytic cell line macrophages, and attenuates inflammatory responses in mouse model. Detailed studies demonstrate that CUL1 interacts with NLRP3 and promotes NLRP3 ubiquitination, but not protein degradation, to repress the NLRP3 inflammasome activation. Moreover, upon inflammatory stimuli, including ATP and nigericin treatments, CUL1 disassociates from NLRP3 to release the repression of the NLRP3 inflammasome. Thus, this study reveals a distinct and unique mechanism underlying the control of systematic activation of the NLRP3 inflammasome.-Wan, P., Zhang, Q., Liu, W., Jia, Y., Ai, S., Wang, T., Wang, W., Pan, P., Yang, G., Xiang, Q., Huang, S., Yang, Q., Zhang, W., Liu, F., Tan, Q., Zhang, W., Wu, K., Liu, Y., Wu, J. Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.

During host–virus co-evolution, cells develop innate immune systems to inhibit virus invasion, while viruses employ strategies to suppress immune responses and maintain infection. Here, we reveal that Zika virus (ZIKV), a re-emerging arbovirus causing public concerns and devastating complications, restricts host immune responses through a distinct mechanism. ZIKV nonstructural protein 5 (NS5) interacts with the host retinoic acid-inducible gene I (RIG-I), an essential signaling molecule for defending pathogen infections. NS5 subsequently represses K63-linked polyubiquitination of RIG-I, attenuates the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3), and inhibits the expression and production of interferon-β (IFN-β), thereby restricting the RIG-I signaling pathway. Interestingly, we demonstrate that the methyltransferase (MTase) domain of NS5 is required for the repression of RIG-I ubiquitination, IRF3 activation, and IFN-β production. Detailed studies further reveal that the conservative active site D146 of NS5 is critical for the suppression of the RIG-I signaling. Therefore, we uncover an essential role of NS5 conservative site D146 in ZIKV-mediated repression of innate immune system, illustrate a distinct mechanism by which ZIKV evades host immune responses, and discover a potential target for anti-viral infection.

Sericin, a bioactive protein forming the outer layer of silk, promotes cell proliferation and cell adhesion, inhibits inflammation, and provides nutrition. Here, we obtain endotoxin-free sericin and explore its potential property in antiviral activity towards infectious diseases. In vesicular stomatitis virus (VSV) infection model, pre-treatment with sericin obviously inhibits VSV replication and reduces organ injury in infected mice. Further studies reveal that pre-incubating cells with sericin results in suppressing the infections of VSV and Enterovirus 71 (EV71) in infected cells. More evidences show that upon virus infection, the levels of interferons (IFNs) are significantly elevated in the cells pre-incubated with sericin as compared to untreated cells, indicating that sericin promotes virus-induced antiviral immune responses. Mechanistically, sericin attenuates cell glycolysis rate and reduces lactate production. Low level of lactate benefitting from sericin treatment facilitates the RIG-I-MAVS signaling pathway to initiate interferon activation. Notably, like sericin, a sericin-derived peptide F5-SP shares the same functions to exert antiviral activity both in vitro and in vivo. Therefore, we report that sericin and sericin-derived peptide F5-SP enhance antiviral innate immune response through inhibiting lactate production, which discovers a promising biomedical application of sericin in the prevention and treatment of viral infectious diseases.

Dengue virus (DENV) infection causes several diseases ranging from dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome characterized by endothelial dysfunction, vascular leakage, and shock. Here, we identify a potential mechanism by which DENV induces tissue injury and vascular leakage by promoting the activation of interleukin (IL)-1β. DENV facilitates IL-1β secretion in infected patients, mice, human peripheral blood mononuclear cells (PBMCs), mouse bone marrow-derived macrophages (BMDMs), and monocyte-differentiated macrophages (THP-1) via activating the NLRP3 inflammasome. The accumulated data suggest that IL-1β probably induces vascular leakage and tissue injury in interferon-alpha/beta receptor 1 deficient C57BL/6 mice (IFNAR -/- C57BL/6), whereas IL-1 receptor antagonist (IL-1RA) alleviates these effects of IL-1β. Finally, administration of recombinant IL-1β protein results in vascular leakage and tissue injury in C57BL/6 mice. Together, the accumulated results demonstrate that IL-1β contributes to DENV-associated pathology and suggest that IL-1RA acts as a potential agent for the treatment of DENV-associated diseases.

The different media were used to study the relationship between seedling growth of Malus hupehensis Rehd and basic physio-chemical properties of growing media.Soil microbe quantity and nitrate reductase activity in the media were also detected.The results showed that:(1) The quantity of soil microbes and the activity of nitrate reductase varied in different media.The quantity of bacteria increased at early stage of seedling growth and decreased at the late stage,in according with the growth rate of seedlings.(2) The soil microbe quantity and nitrate reductase activity in loam soil were the highest throughout the growing period.Furthermore,the stem diameter of the seedlings was the largest and quality was the best.(3) The seedlings growing in sandy soil developed their roots earlier and had the highest root-shoot ratio.However,the soil microbe quantity and nitrate reductase activity were the lowest in the treatments throughout the growing period.This study suggested that the growth of M.hupehensis Rehd seedling was prompted by nutrition and physical characters of loam soil.