Salmonid alphavirus non-structural protein 2 is a key protein that activates the NF-κB signaling pathway to mediate inflammatory responses.

Salmonid alphavirus (SAV) infection of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) causes pancreas disease (PD) with typical inflammatory responses, such as necrosis of the exocrine pancreas, cardiomyopathy and skeletal myopathy. However, the pathogenic mechanism underlying SAV infection is still unclear. Inflammation may cause damage to the body, but it is a defense response against infection by pathogenic microorganisms, of which nuclear factor-kappa B (NF-κB) is the main regulator. This study revealed that SAV can activate NF-κB, of which the viral nonstructural protein Nsp2 is the major activating protein. SAV activates the NF-κB signaling pathway by simultaneously up-regulating TLR3, 7, 8 and then the expression of the signaling molecule myeloid differentiation factor 88 (Myd88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). We found that Nsp2 can induce IκB degradation and p65 phosphorylation and transnucleation, and activate NF-κB downstream inflammatory cytokines. Nsp2 may simultaneously activate NF-κB through TLR3,7,8-dependent signaling pathways. Overexpression of Nsp2 can up-regulate mitochondrial antiviral signaling protein (MAVS) and then promote the expression of IFNa1 and antiviral protein Mx, which inhibits viral replication. This study shows that Nsp2 acts as a key activator protein for the NF-κB signaling pathway, which induces inflammation post-SAV infection. This study systematically analyzes the molecular mechanism of SAV activation of the NF-κB signaling pathway, and provides a theoretical basis for revealing the mechanism of innate immune response and inflammatory injury caused by SAV.

Contamination assessment, health risk evaluation, and source identification of heavy metals in the soil-rice system of typical agricultural regions on the southeast coast of China.

To quantitatively assess heavy metal accumulation and potential ecological and human health risks as well as analyze the sources of metals in a typical soil-rice system located on the southeast coast of China, 120 topsoil samples and corresponding rice grain samples were collected across the study area. The concentrations of As, Cd, Pb, Cr, Hg, Zn, Cu, and Ni were analyzed. The results revealed that Hg, Cd, and Cu were the main pollutants in soils. Besides, according to geo-accumulation value of Hg, 18.3% of samples were at or above moderate contamination levels. Additionally, the soil was in moderate ecological risk from combined heavy metal pollution, and 49.7% and 27.0% of this risk could be attributed to Hg and Cd pollution, respectively, due to their high toxic-response factors. For the rice samples, Cd content showed the highest biological accumulation coefficient value (40.8%) in rice grains and was slightly greater than its maximum allowable value (MAV) (0.2 mg/kg) in 7.5% of samples, whereas the other metals were all lower than their corresponding MAVs. Heavy metal exposure (especially As exposure) via rice consumption causes significant carcinogenic and non-carcinogenic risks to adults, and non-carcinogenic risk to children, while the carcinogenic risk to children was at tolerable level. Greater rice consumption might be responsible for the greater health risk to adults than children. Natural sources (loaded heavily with Cr and Ni) such as lithogenic components and soil parent materials, agricultural activities (loaded heavily with Cd, Cu, and Zn), especially excessive use of pesticides and fertilizers, and industrial activities (loaded heavily with Hg, Pb, and As) including vehicle emissions, coal combustion, and those of the textile and chemical industries were identified as the main sources. Effective regulations should be enforced to guarantee the safety of farm produce and protect ecological and human health in the study area.

Staging Surgery for The Treatment of Aortic Arch Aneurysm Combined with Aberrant Bilateral Subclavian Artery, Persistent Left Superior Vena Cava and Airway Compression: A Case Report.

BACKGROUND: To describe staging surgery for the treatment of a patient with aortic arch aneurysm combined with aberrant bilateral subclavian artery, persistent left superior vena cava (PLSVC), and airway compression. CASE REPORT: A 42-year-old female was hospitalized for aortic arch aneurysm involving aberrant bilateral subclavian artery, PLSVC, and airway compression. The patient's aneurysm was successfully treated by stage I surgery, including total aortic arch replacement and stented elephant trunk procedure and stage II surgery, including tracheal stenting and tracheotomy. Aortic CTA examination showed an unobstructed lumen and a good stent position without tracheal stent migration. Regular postoperative follow-up showed no complications, such as dyspnea, cough, and sputum, or other discomfort symptoms. CONCLUSIONS: Total aortic arch replacement, elephant trunk surgery, and second-stage tracheal stent surgery are effective and safe for the treatment of aortic arch aneurysm combined with aberrant bilateral subclavian artery, PLSVC, and airway compression.

The association between heavy metal soil pollution and stomach cancer: a case study in Hangzhou City, China.

Stomach cancer (SC) is a severe health burden, with nearly half of the world's cases found in China. Noticeably, the emissions of heavy metals into the environment have increased alongside rapid urbanization and industrialization in China. However, as regards carcinogenic associations, the relationship between heavy metals and SC is yet unclear. Based on 9378 newly diagnosed SC cases in Hangzhou City from 2009 to 2012, this work is concerned with the quantitative characterization of the spatial distribution pattern of SC incidence and its geographical association with soil heavy metals by means of a novel geographical model. The results show that (a) Cd is one of the severe soil pollutants in Hangzhou; (b) higher SC incidence clusters are in central Hangzhou, whereas lower clusters are found in the northeast and southwest with a male to female incidence ratio about 2.2:1; (c) although when considered separately, the heavy metals in this work do not have a considerable impact on the distribution of SC incidence in Hangzhou City, nevertheless, the joint effects of multiple heavy metals have significant impacts on SC risk. The present work calls for a rigorous quantitative assessment of the integrated heavy metal soil pollution and its effects on SC incidence.

Molecular mechanism of Gd@C82(OH)22 increasing collagen expression: Implication for encaging tumor.

Gadolinium-containing fullerenol Gd@C82(OH)22 has demonstrated low-toxicity and highly therapeutic efficacy in inhibiting tumor growth and metastasis through new strategy of encaging cancer, however, little is known about the mechanisms how this nanoparticle regulates fibroblast cells to prison (instead of poison) cancer cells. Here, we report that Gd@C82(OH)22 promote the binding activity of tumor necrosis factor (TNFα) to tumor necrosis factor receptors 2 (TNFR2), activate TNFR2/p38 MAPK signaling pathway to increase cellular collagen expression in fibrosarcoma cells and human primary lung cancer associated fibroblasts isolated from patients. We also employ molecular dynamics simulations to study the atomic-scale mechanisms that dictate how Gd@C82(OH)22 mediates interactions between TNFα and TNFRs. Our data suggest that Gd@C82(OH)22 might enhance the association between TNFα and TNFR2 through a "bridge-like" mode of interaction; by contrast, the fullerenol appears to inhibit TNFα-TNFR1 association by binding to two of the receptor's cysteine-rich domains. In concert, our results uncover a sequential, systemic process by which Gd@C82(OH)22 acts to prison tumor cells, providing new insights into principles of designs of cancer therapeutics.

Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells.

Infection of polarized intestinal epithelial cells by porcine epidemic diarrhea virus (PEDV) was characterized. Indirect immunofluorescence assay, real-time PCR, and transmission electron microscopy confirmed PEDV can be successfully propagated in immortalized swine small intestine epithelial cells (IECs). Infection involved porcine aminpeptidase N (pAPN), a reported cellular receptor for PEDV, transient expression of pAPN and siRNA targeted pAPN increased and decreased the infectivity of PEDV in IECs, respectively. Subsequently, polarized entry into and release from both Vero E6 and IECs was analyzed. PEDV entry into polarized cells and pAPN grown on membrane inserts occurs via apical membrane. The progeny virus released into the medium was also quantified which demonstrated that PEDV is preferentially released from the apical membrane. Collectively, our data demonstrate that pAPN, the cellular receptor for PEDV, mediates polarized PEDV infection. These results imply the possibility that PEDV infection may proceed by lateral spread of virus in intestinal epithelial cells.

25-(OH)VitD3, as a risk indicator in diagnosis of adenocarcinoma.

Vitamin D (VitD) comes from sunlight exposure and food intake. Apart from regulating calcium homeostasis and bone function, its levels also associate with the presence of development of adenocarcinoma. VitD can interact with VitD receptor (VDR), which heterodimerizes with retinoic X receptor (RXR) and then induces transcription of proteins that function in cell proliferation, differentiation, apoptosis, and angiogenesis. We reviewed and discussed the genes and their associated polymorphisms involved in the correlation between development of adenocarcinoma and VitD deficiency to highlight how VitD may be instrumental in cancerization. Furthermore, pilot epidemiological data show that the detection of 25-hydroxy-Vitamin D3 ((36.5±10.7 nmol/L, n=129) vs (81.4±19.8 nmol/L, n=81)) can be a promising approach in cancer diagnosis. In this review, we suggest that 25-hydroxy-Vitamin D3 can act as an indicator and/or risk assessment factor in early diagnosis, prognosis and treatment of adenocarcinoma.

A monoclonal antibody against transmissible gastroenteritis virus generated via immunization of a DNA plasmid bearing TGEV S1 gene.

Transmissible gastroenteritis virus (TGEV) is a member of the coronaviruses. The viral spike (S) protein of TGEV mediates interaction between TGEV and its susceptible cells. Herein, DNA plasmid bearing TGEV S1 gene (the N terminal half of TGEV S gene) was used to immunize BALB/c mice followed by generation of a monoclonal antibody (MAb) using the hybridoma technique. The generated MAb (1H4) was identified by ELISA. Immunofluorescence assays showed that MAb 1H4 was able to detect infection of cells with TGEV. The MAb 1H4 distinguished TGEV from other control viruses. Additionally, although the type of MAb 1H4 was IgM, it could reduce cell infection by TGEV in a dose-dependent manner.