During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

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␤-Catenin is a key molecule involved in both cell adhesion and Wnt signaling pathway. However, the exact relationship between these two roles has not been clearly elucidated. Tyrosine phosphorylation of ␤-catenin was shown to decrease its binding to E-cadherin, leading to decreased cell adhesion and increased ␤-catenin signaling. We have previously shown that receptor-like proteintyrosine phosphatase PCP-2 localizes to the adherens junctions and directly binds and dephosphorylates ␤-catenin, suggesting that PCP-2 might regulate the balance between signaling and adhesive ␤-catenin. Here we demonstrate that PCP-2 can inhibit both the wild-type and constitutively active forms of ␤-catenin in activating target genes such as c-myc. The phosphatase activity of PCP-2 is required for this effect since loss of catalytic activity attenuates its inhibitory effect on ␤-catenin activation. Expression of PCP-2 in SW480 colon cancer cells can lead to stabilization of cytosolic pools of ␤-catenin perhaps, by virtue of their physical interaction. PCP-2 expression also leads to increased membrane-bound E-cadherin and greater stabilization of adherens junctions by dephosphorylation of ␤-catenin, which could further sequester cytosolic ␤-catenin and thus inhibit ␤-catenin mediated nuclear signaling. Furthermore, SW480 cells stably expressing PCP-2 have a reduced ability to proliferate and migrate. Thus, PCP-2 may play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may be an alternative mechanism for activating ␤-catenin signaling.Reversible and dynamic tyrosine phosphorylation is controlled by the opposing actions of protein-tyrosine kinases and protein-tyrosine phosphatases (PTPs) 2 (1). PTPs are a large family that is broadly classified into receptor-like protein-tyrosine phosphatases (RPTPs) and cytosolic PTPs (2). A subfamily of RPTPs containing an MAM (Meprin/A5/PTP mu) domain in the ectodomain followed by an Ig-like domain and fibronectin type III repeats is defined as the MAM-subfamily PTPs (MAM-PTPs), which include PCP-2, PTP, PTP, and PTP (3, 4). These RPTPs also contain a single membrane-spanning region with two cytoplasmic PTP domains. The intracellular juxtamembrane domain of these RPTPs contains a region that is homologous to the conserved intracellular domain of the cadherins (5).Cadherins are a family of calcium-dependent adhesion molecules that play an essential role in the formation of the cell-cell contacts termed adherens junctions. Cadherin-mediated cell-cell adhesion is important for development and maintenance of epithelial tissue integrity, and its disturbance contributes to the invasive and metastatic phenotype of epithelial tumors. Through their intracellular domains, cadherins associate with molecules of the Armadillo superfamily including ␤-catenin, which links them to the actin cytoskeleton via the ␣-catenin bridge (6, 7). In addition to its adhesive functions, ␤-catenin has also been found to serve as a key component in Wnt signaling (8,9). When relea...

Recent studies have revealed that the use of probiotics is an alternative to control marine aeromonas. However, few probiotics are available against Aeromonas hydrophila infections in eels. In the present study, a potential antagonistic strain G1 against the eel-pathogenic A. hydrophila was isolated from sediment underlying brackish water. Its extracellular products with antibacterial activities were shown to be stable under wide range of pH, temperature, and proteinase K. It was initially identified as Bacillus amyloliquefaciens using API identification kits and confirmed to be B. amyloliquefaciens strain (GenBank accession number DQ422953) by phylogenetic analysis. In addition, it was shown to be safe for mammalians, had a wide anti-A. hydrophila spectrum, and exhibited significant effects on inhibiting the growth of the eel-pathogenic A. hydrophila both in vitro and in vivo. To the best of our knowledge, this is the first report on a promising antagonistic Bacillus amyloliquefaciens strain from brackish water sediment against eel-pathogenic A. hydrophila.

Acute myeloid leukemia (AML) is a disorder involving hematopoietic stem cells, characterized by blockage of hematopoietic cell differentiation and an increase in clonal neoplastic proliferation. AML is associated with poor patient outcome. PBK/TOPK is a protein kinase derived from PDZ-binding kinase (PBK)/T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK). Previous studies have shown that PBK/TOPK is expressed in hematologic tumors. In the present study, we aimed to investigate the role of PBK/TOPK in promyelocyte proliferation and to clarify the molecular mechanism. PBK/TOPK knockdown (KD) significantly decreased cell proliferation and viability in the NB4 and HL-60 promyelocytes. PBK/TOPK KD resulted in G2/M cell cycle arrest that attributed to a decrease in cdc2 and cyclin B expression. In addition, PBK/TOPK KD caused apoptosis, as evidenced by activation of the mitochondrial apoptotic pathway and an increase in TUNEL-positive cells. PBK/TOPK KD induced mitochondrial dysfunction and ROS generation, and inhibition of mitochondrial dysfunction and ROS production suppressed PBK/TOPK KD-induced cell cycle arrest and apoptosis. Moreover, PBK/TOPK KD decreased Nrf2 expression and ARE-binding activity. Overexpression of Nrf2 inhibited the PBK/TOPK KD-induced decrease in cdc2 and cyclin B expression and cell cycle arrest, and blocked ROS production and apoptosis. Based on literature and our results, it was demonstrated that Nrf2 may be a crucial regulator that mediates PBK/TOPK-exerted promotion of cell proliferation. PBK/TOPK stabilizes Nrf2, strictly regulates the ROS level, promotes cell cycle progression and inhibits apoptosis, contributing to the proliferation of promyelocytes. Our results provide new insights into the molecular mechanism of PBK/TOPK-mediated promyelocyte proliferation and shed light on the pathogenesis of AML.

Background The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. MethodsWe did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings We enrolled patients visiting fever clinics fromJan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1•9%) were considered as suspected cases, with 188 (0•4% of all patients, 18•7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4•16, 95% CI 2•74-6•33; p<0•0001), fatigue (OR 1•56, 1•01-2•41; p=0•043), white blood cell count less than 4 × 10⁹ per L (OR 2•44, 1•28-4•64; p=0•0066), lymphocyte count less than 0•8 × 10⁹ per L (OR 1•82, 1•00-3•31; p=0•049), ground glass opacity (OR 1•95, 1•32-2•89; p=0•0009), and having both lungs affected (OR 1•54, 1•04-2•28; p=0•032) were independent risk factors for confirmed COVID-19.Interpretation The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease.

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Saprolegnia species have been implicated for significant fungal infections of both living and dead fish as well as their eggs. In the present study, an oomycete water mould (strain HP) isolated from yellow catfish (Peleobagrus fulvidraco) eggs suffering from saprolegniosis was characterized both morphologically and from ITS sequence data. It was initially identified as a Saprolegnia sp. isolate based on its morphological features. The constructed phylogenetic tree using neighbour joining method indicated that the HP strain was closely related to Saprolegnia ferax strain Arg4S (GenBank accession no. GQ119935), that had previously been isolated from farming water samples in Argentina. In addition, the zoospore numbers of strain HP were markedly influenced by a variety of environmental variables including temperature, pH, formalin and dithiocyano-methane. Its zoospore formation was optimal at 20 °C and pH 7, could be well inhibited by formalin and dithiocyano-methane above 5 mg/L and 0.25 mg/L, respectively. To our knowledge, this is the first report on the S. ferax infection in the hatching yellow catfish eggs.