Evidence linking exposure of fish primary macrophages to antibiotics activates the NF-kB pathway.

Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway

Seasonal Characteristics of Black Carbon Aerosol and its Potential Source Regions in Baoji, China

Continuous measurements of black carbon (BC) aerosol were made at a midsized urban site in Baoji, China, in 2015. The daily average mass concentrations varied from 0.6 to 11.5 mu g m(-3), with an annual mean value of 2.9 +/- 1.7 mu g m(-3). The monthly variation indicated that the largest loading of BC occurred in January and the smallest in June. The mass concentrations exhibited strong seasonality, with the highest occurring in winter and the lowest in summer. The large BC loadings in winter were attributed to the increased use of fuel for domestic heating and to stagnant meteorological conditions, whereas the low levels in summer were related to the increase in precipitation. BC values exhibited similar bimodal diurnal patterns during the four seasons, with peaks occurring in the morning and evening rush hours and an afternoon trough, which was associated with local anthropogenic activities and meteorological conditions. A potential source contribution function model indicated that the effects of regional transport mostly occurred in spring and winter. The most likely regional sources of BC in Baoji were southern Shaanxi province, northwestern Hubei province, and northern Chongqing during spring, whereas the northeastern Sichuan Basin was the most important source region during winter

Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport

Background: Duchenne musclar dystrophy (DMD) is an X-linked recessive disease caused by mutations of dystrophin gene, there is no effective treatment for this disorder at present. Plasmidmediated gene therapy is a promising therapeutical approach for the treatment of DMD. One of the major issues with plasmid-mediated gene therapy for DMD is poor transfection efficiency and distribution. The herpes simplex virus protein VP22 has the capacity to spread from a primary transduced cell to surrounding cells and improve the outcome of gene transfer. To improve the efficiency of plasmid-mediated gene therapy and investigate the utility of the intercellular trafficking properties of VP22-linked protein for the treatment for DMD, expression vectors for C-terminal versions of VP22-microdystrophin fusion protein was constructed and the VP22-mediated shuttle effect was evaluated both in vitro and in vivo. Results: Our results clearly demonstrate that the VP22-microdystrophin fusion protein could transport into C2C12 cells from 3T3 cells, moreover, the VP22-microdystrophin fusion protein enhanced greatly the amount of microdystrophin that accumulated following microdystrophin gene transfer in both transfected 3T3 cells and in the muscles of dystrophin-deficient (mdx) mice. Conclusion: These results highlight the efficiency of the VP22-mediated intercellular protein delivery for potential therapy of DMD and suggested that protein transduction may be a potential and versatile tool to enhance the effects of gene delivery for somatic gene therapy of DMD.National Natural Science Foundation of China (30370510, 30170337); CMB Fund (4209347); the Key Project of the State Ministry of Public Health (2001321); and National Nature Science Foundation of China (30400322)

Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide with inflammation and injury in airway epithelial cells. However, few treatment options effectively reduce severity. We previously found that Nur77 is involved in lipopolysaccharide-induced inflammation and injury of lung tissue. Here, we established an in vitro model of COPD-related inflammation and injury in 16-HBE cells induced by cigarette smoke extract (CSE). In these cells, Nur77 expression and localization to the endoplasmic reticulum (ER) increased following CSE treatment, as did ER stress marker (BIP, ATF4, CHOP) expression, inflammatory cytokine expression, and apoptosis. The flavonoid derivative, named B6, which was shown to be a modulator of Nur77 in previous screen, molecular dynamics simulation revealed that B6 binds strongly to Nur77 through hydrogen bonding and hydrophobic interactions. Treating CSE-stimulated 16-HBE cells with B6 resulted in a reduction of both inflammatory cytokine expression and secretion, as well as attenuated apoptosis. Furthermore, B6 treatment resulted in a decrease in Nur77 expression and translocation to the ER, which was accompanied by a concentration-dependent reduction in the expression of ER stress markers. Meanwhile, B6 played a similar role in CSE-treated BEAS-2B cells. These combined effects suggest that B6 could inhibit inflammation and apoptosis in airway epithelial cells after cigarette smoke stimulation, and support its further development as a candidate intervention for treating COPD-related airway inflammation

Mycoediketopiperazine, a novel fungal metabolite from a Papularia sp.

A novel metabolite, mycoediketopiperazine, was isolated from a fungi culture (M-204036). Its structure and absolute stereochemistry was established by spectroscopic studies, including single-crystal X-ray diffraction analysis. (C) 2005 Published by Elsevier Ltd

Synaptotagmin-like protein 1 is a potential diagnostic and prognostic biomarker in endometrial cancer based on bioinformatics and experiments

Abstract Endometrial cancer (EC) is one of the most common gynecologic malignancies. Identification of potential EC biomarkers is essential to improve the prognosis and development of therapies against EC. Synaptotagmin-like protein 1 (SYTL1), as a small GTPase Rab27 effector, mainly plays a role in vesicle trafficking and cytotoxic granule exocytosis in lymphocytes. However the role of SYTL1 in EC remains uncertain. We performed a comprehensive assessment of the relationship between SYTL1 and patient diagnosis and prognosis by analysis of EC patients’ data from TCGA. We employed the LinkedOmics and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to analyze the biological function of SYTL1 in EC. In addition, the correlation between SYTL1 expression and its DNA methylation was performed by using cBioportal, UALCAN, TCGA Wanderer and MethSurv databases. We further assessed the link between SYTL1 and tumor-infiltrating immune cells by using gene set variation analysis (GSVA). Results We found that SYTL1 was highly expressed in EC patients and cell lines. And increased expression of SYTL1 was associated with age, clinical stage, histological type, histological grade and good overall survival (OS).SYTL1 DNA methylation is negatively associated with SYTL1 expression and UCEC patients’ OS. SYTL1 expression is closely correlated with immune infiltration. Furthermore, we carried out in vitro experiments to verify the results of bioinformatic analysis. Conclusion Our results demonstrated that the elevation of SYTL1 expression is associated with good OS and SYTL1 might be a potential diagnostic and prognostic marker in EC

COPPER (I) IODIDE-CATALYZED SOLVENT-FREE SYNTHESIS OF alpha-AMINOPHOSPHONATES

National Natural Science Foundation of China [40806032]; Natural Science Foundation of Fujian Province of China [2009J05099, 2011J05101, 2010NZ0001-2]A method for the synthesis of alpha-aminophosphonates through the three-component coupling reaction of aldehydes, amines, and diisopropyl phosphite using copper (I) iodide salt catalyst is demonstrated, The reaction is highly efficient, economic, and also environment friendly. [Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Table S1, Figures S1-S9.

A bi-material property based FE modelling method for progressive damage analyses of composite double-lap bolted joints

A bi-material property method was proposed to describe mechanical properties of the unidirectional composite lamina. It divided the lamina into the fiber layer and the resin layer, which have different material properties and are responsible for the intra-laminar and inter-laminar properties, respectively. Furthermore, a finite element modelling method with the composite lamina simulated by the bi-material property method was presented. Combined with a Hashin-type failure criterion and a micromechanics-based material degradation model, a novel progressive damage model (PDM) was constructed for typical double-lap bolted joints. To validate the novel PDM, four double-lap, single-bolt joints with various width-to-hole-diameter ratios were designed and quasi-static tensile tests of the joints were performed. Numerical results of the novel PDM show better agreements with the experimental outcomes than the traditional PDMs. Besides, the novel PDM can describe the inter-laminar damage more precisely via a more reasonable simulation for the inter-laminar property of the lamina, and can also obtain more accurate deformation of the hole along the thickness direction of the laminate. Furthermore, influences of the width-to-hole-diameter ratio W/D on failure behaviours of the double-lap, single-bolt joint were revealed, and an optimal width-to-hole-diameter ratio was recommended for engineering practice. Combined with our previous study on effects of the end-distance-to-hole-diameter ratio E/D, a failure mode map with varying W/D and E/D was determined for the double-lap bolted joint. It is helpful for designers to seek safer designs of composite bolted joints because the W/D and E/D are key geometrical parameters that significantly affect failure behaviours of the joints. Keywords: Composites, Bolted joints, Bi-material property, Finite element modelling, Progressive damage analyses, Failure mode ma

Syntheses, characterizations, and crystal structures of phosphonopeptides

alpha-Aminophosphonic acids and their derivatives, as phosphorus analogs of amino acids, have attracted much attention as they show a range of biological activities. In this paper, dialkyl phenyl(4-pyridylcarbonylamino)methylphosphonates were synthesized via the Mannich reaction (Yuan et al., Synthesis 1990, 3, 256) and peptide coupling. Their structures were confirmed by elemental analysis, IR, H-1 NMR, C-13 NMR, and MS. X-ray diffraction data of compounds (2a, 2b, 2c) were reported respectively. The antibacterial and antitumor activities of these compounds are first reported in this paper. (c) 2007 Wiley Periodicals, Inc