Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important causative agents to swine industry, which has been epidemic more than 30 years. The emergence and recombination of new virus strains bring great challenges to the prevention and control of PRRSV. In the present study, we reported and characterized a novel PRRSV strain, designated as JS2021NADC34, which was for the first time isolated from clinical samples in Jiangsu province, China. Phylogenetic analysis demonstrated that JS2021NADC34 belonging to sublineage 1.5 of PRRSV-2 and was highly related to NADC34-like strains. Genetically, JS2021NADC34 strain had a continuous 100 aa depletion in NSP2, as compared to VR-2332 strain, which was consistent with most reported NADC34-like strains. Moreover, there were several amino acid substitutions occurred in the antigenic regions of GP2-GP5. Similar to other reported NADC34-like PRRSV in China, JS2021NADC34 had no recombination with other domestic strains, which indicates this sublineage of PRRSV may be directly transported from the United States and have not undergone extensive mutation and recombination with local strains yet.

Advances in the understanding of growth hormone-producing adenomas (GHomas) are ongoing, but current therapy is limited by moderate and variable efficacy and in need of life-long treatment. In this study, the molecular signaling pathway related to GHoma was investigated by proteomics and transcriptomics. The differentially expressed proteins and genes were significantly enriched in Extracellular Matrix-Receptor Interactions, Notch Signaling, Basal Cell Carcinoma Signaling, JAK-STAT3, Wnt Signaling, and Glioblastoma Multiforme Signaling by Ingenuity Pathway Analysis. Furthermore, the Notch2/Delta-like canonical Notch ligand (DLL) signaling pathway was identified to be associated with tumorigenesis and invasiveness of GHoma. In 76 patients, Notch2 and DLL3 were upregulated in invasive compared to those in non-invasive GHoma ( p < 0.05). Disease-free survival was significantly longer in patients with low, compared with high, DLL3 expression ( p = 0.027). Notch 2 knockdown inhibited cell migration in both GH3 cells and primary GHoma cells, along with downregulation of the mRNA expression of related genes. DAPT, a γ-secretase inhibitor, inhibited tumor growth and invasion in vivo and in vitro and suppressed the release of growth hormone in primary GHoma cells. The involvement of Notch2/DLL3 signaling in GHoma progression warrants additional study of Notch inhibitor, DAPT, as a potential GHoma treatment. Importance of the Study Current treatments of GH adenomas (GHomas) are limited by their moderate and variable efficacy and in need of life-long treatment. We found that the Notch2/Delta-like Notch ligand 3 (DLL3) signaling pathway was active in GHoma tumorigenesis, progression, and invasion. The γ-secretase inhibitor DAPT is of potential use in GHoma treatment targeting Notch signaling.

Although astrovirus causes enteric diseases and encephalitis in humans, and nephritis and hepatitis in poultry, the infection of astrovirus is thought to be self-limiting. However, little is known about its molecular mechanism. In this study, we found a novel goose astrovirus GAstV-GD and its ORF2 could efficiently activate the innate immune response and induce a high level of OASL in vitro and in vivo. The truncation assay for ORF2 further revealed that the P2 domain of ORF2 contributed to stimulate OASL, whereas the acidic C-terminus of ORF2 attenuated such activation. Moreover, the over-expression and knockdown of OASL could efficiently restrict and promote the viral replication of GAstV-GD, respectively. Our data not only given novel insights for elucidating the self-limiting infection of the astrovirus but also provided virus and host targets for fighting against astroviruses. IMPORTANCE Astroviruses cause gastroenteritis and encephalitis in human, and nephritis, hepatitis and gout disease in poultry. However, the host immune response activated by astrovirus is mostly unknown. Here, we found that a novel goose astrovirus GAstV-GD and its ORF2 protein could efficiently induce a high level of OASL in vitro and in vivo, which could feedback to restrict the replication of GAstV-GD, revealing novel innate molecules triggered by astroviruses, and highlighting the ORF2 of GAstV-GD and OASL can be as potential antiviral targets for astroviruses.

Nonfunctioning pituitary adenomas (NFPAs) are the most prevalent type of pituitary macro-adenoma. Clarifying the relationship between NFPA markers and disease progression or recurrence could provide a basis for administration of adjuvant treatments. The present study examined the expression levels of high-mobility group (HMG)A1, Ki-67, mouse double minute 2 homolog (MDM2), and retinoblastoma (RB)with respect to NFPA recurrence. Immunohistochemistry was carried out using antibodies to Ki-67, MDM2, HMGA-1, and RB on tissue microarray slides of a cohort of 35 paired NFPA samples of primary and recurrence/regrowth tumors. Based on postoperative magnetic resonance imaging data, tumors were classified as recurrence (n = 20) included primary and recurrent tumors or regrowth (n = 15) included primary and regrowth tumors, which are paired. Protein expression was classified as negative or positive according to the H-score method and was analyzed with respect to clinical and pathological findings. MDM2-positive cases accounted for11/20 primary and 19/20 s recurrent tumors (χ2 = 8.533, P = 0.003), and 9/15 primary tumors and 15/15 s regrowth tumors (χ2 = 7.5, P = 0.006). MGA1-positive cases represented 9/20 primary tumors and 16/20 s recurrent tumors (χ2 = 5.227, P = 0.022), and 4/15 primary tumors and 12/15 s regrowth tumors (χ2 = 8.571, P = 0.003). There was no statistically significant difference in Ki-67 expression between primary and second recurrent/regrowth tumors although theKi67 labeling index was higher in the latter groups. RB was highly expressed in all groups with no significant difference between them. HMGA1 and MDM2 were more highly expressed in recurrence/regrowth cases of NFPA than in primary NFPA. HMGA1 and MDM2 are biomarkers and potential drug targets for NFPA treatment.

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