Leucine-rich repeat-containing G protein-coupled receptor 4 facilitates vesicular stomatitis virus infection by binding vesicular stomatitis virus glycoprotein.

Vesicular stomatitis virus (VSV) and rabies and Chandipura viruses belong to the Rhabdovirus family. VSV is a common laboratory virus to study viral evolution and host immune responses to viral infection, and recombinant VSV-based vectors have been widely used for viral oncolysis, vaccination, and gene therapy. Although the tropism of VSV is broad, and its envelope glycoprotein G is often used for pseudotyping other viruses, the host cellular components involved in VSV infection remain unclear. Here, we demonstrate that the host protein leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is essential for VSV and VSV-G pseudotyped lentivirus (VSVG-LV) to infect susceptible cells. Accordingly, Lgr4-deficient mice had dramatically decreased VSV levels in the olfactory bulb. Furthermore, Lgr4 knockdown in RAW 264.7 cells also significantly suppressed VSV infection, and Lgr4 overexpression in RAW 264.7 cells enhanced VSV infection. Interestingly, only VSV infection relied on Lgr4, whereas infections with Newcastle disease virus, influenza A virus (A/WSN/33), and herpes simplex virus were unaffected by Lgr4 status. Of note, assays of virus entry, cell ELISA, immunoprecipitation, and surface plasmon resonance indicated that VSV bound susceptible cells via the Lgr4 extracellular domain. Pretreating cells with an Lgr4 antibody, soluble LGR4 extracellular domain, or R-spondin 1 blocked VSV infection by competitively inhibiting VSV binding to Lgr4. Taken together, the identification of Lgr4 as a VSV-specific host factor provides important insights into understanding VSV entry and its pathogenesis and lays the foundation for VSV-based gene therapy and viral oncolytic therapeutics.

Chemotherapy-induced uridine diphosphate release promotes breast cancer metastasis through P2Y6 activation.

Although purinergic signaling is important in regulation of immune responses, the therapeutic potential of it in the tumor microenvironment is little defined. In this study, we demonstrate that UDP/P2Y6 signaling facilitates breast cancer metastasis both in vitro and in vivo. We found that P2Y6 is not only aberrantly expressed and mutated in most tumor types, but also highly correlated with poor prognosis in breast cancer patients. Furthermore, the migration and invasion of breast cancer cells was obviously increased by UDP and blocked by P2Y6 specific inhibitor MRS2578 and P2Y6 shRNA. Similar results was also found in breast cancer cell metastasis mouse model. Interestingly, the endogenous agonist UDP was released significantly by doxorubicin treated cells. In addition, the expression and enzyme activity of MMP-9 were both promoted by UDP and inhibited by MRS2578 or P2Y6 shRNA. Furthermore, UDP-induced cell invasion was blocked by an MMP-9 inhibitor. Mechanistically, the MAPKs and NF-κB signaling pathways, known to be involved in regulation of MMP-9 expression, were both activated by UDP. Taken together, our study reveals a relationship between extracellular danger signals and breast cancer metastasis, which suggests the potential therapeutic significance of UDP/P2Y6 signaling in cancer therapy.

Experimental study on the effects of H(2)O on PCDD/Fs formation by de novo synthesis in carbon/CuCl(2) model system.

The effects of H(2)O vapor on de novo synthesis of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and biphenyls (PCB) were investigated at two levels (none and 10 vol.%) in various model systems containing five different carbons, CuCl(2), and quartz, exposed to a flow of 10% O(2)/N(2) at 300 degrees Celsius. The influence of H(2)O was studied on (1) speciation and behavior of copper compounds, (2) catalytic oxidation of carbons of distinct reactivity, and (3) formation of organic chlorine compounds, with the aim to investigate any effects on de novo synthesis. It is found that H(2)O converts CuCl(2) to CuCl(2) x CuO, and finally to CuO in a flow of 10% O(2)/N(2) at 300 degrees Celsius and that it decreases of organic chlorine (C-Cl) formation. When CuCl(2) is supported on carbon, the addition of H(2)O promotes the catalytic oxidation of this carbon. When CuCl(2) is supported on quartz, however, H(2)O inhibits carbon oxidation. A decrease in chlorination level of PCDD/Fs and PCBs with water addition is observed for all (six) model ashes; yet this addition affects the yields of PCDD/Fs and PCBs differently. Under the experimental conditions tested H(2)O does not react with Cu(2)Cl(2), which is the catalyst of carbon oxidation. On the basis of the experimental results, the following mechanism is proposed: conversion of CuCl(2) into CuO which is less reactive in de novo synthesis and promotion of catalytic oxidation of carbon by Cu(2)Cl(2).

Mechanochemical decomposition of pentachlorophenol by ball milling.

The mechanochemical dechlorination of pentachlorophenol (PCP) was studied using CaO and SiO2 powder as additives. The effects of the milling time and additives on the dechlorination rate were investigated. The resulting product was characterized by X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), thermogravimetric analysis (TG) and ion chromatography (IC). It is found that grinding operation could dechlorinate PCP, with the formation of inorganic chloride and amorphous carbon. The addition of quartz to the grinding mixture facilitated dechlorination. On the basis of the experimental results, the decomposition mechanism was proposed. Decomposition predominantly proceeds through rupture of C-Cl bond in PCP molecule, followed by the formation of inorganic chlorides.