Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses.

Manganese (Mn) is essential for many physiological processes, but its functions in innate immunity remain undefined. Here, we found that Mn2+ was required for the host defense against DNA viruses by increasing the sensitivity of the DNA sensor cGAS and its downstream adaptor protein STING. Mn2+ was released from membrane-enclosed organelles upon viral infection and accumulated in the cytosol where it bound directly to cGAS. Mn2+ enhanced the sensitivity of cGAS to double-stranded DNA (dsDNA) and its enzymatic activity, enabling cGAS to produce secondary messenger cGAMP in the presence of low concentrations of dsDNA that would otherwise be non-stimulatory. Mn2+ also enhanced STING activity by augmenting cGAMP-STING binding affinity. Mn-deficient mice showed diminished cytokine production and were more vulnerable to DNA viruses, and Mn-deficient STING-deficient mice showed no increased susceptibility. These findings indicate that Mn is critically involved and required for the host defense against DNA viruses.

High-order rational-type solutions of the analogous (3+1)-dimensional Hirota-bilinear-like equation.

In this article, a new dynamical system equation named the (3+1)-dimensional Hirota-bilinear-like equation (HBLE) was constructed. The generalized Hirota bilinear method was applied to obtain this new HBLE in (3+1) dimensions. This new HBLE possesses a similar bilinear form to the original (3+1)-dimensional Hirota bilinear equation, but with additional nonlinear terms. A set of high-order rational solutions is constructed for the given equation, generated from polynomial solutions to the associated generalized bilinear equation. The analyticity conditions of the resulting solutions were investigated and six groups of general solutions were derived. In addition, the shape and surface of the high-order rational function solutions and their dynamic behaviors were studied by utilizing Maple.

Quantitative structure-toxicity relationships of halobenzoquinone isomers on DNA reactivity and genotoxicity.

Halobenzoquinones (HBQs) are an emerging class of drinking water disinfection byproducts that have been predicted as bladder carcinogens. However, data on the genotoxicity of HBQs are still scarce. This study performed a quantitative structure-toxicity relationship (QSTR) analysis of HBQ isomers on DNA reactivity and genotoxicity. The interaction of HBQs with calf thymus DNA (ct-DNA) was studied using multi-spectroscopic and molecular docking techniques. UV-Vis absorption spectra observed a significant hyperchromic effect with the increase of HBQ concentration. The fluorescence intensity of both probe-ct-DNA decreased with the increasing concentration of HBQs, indicating that the interaction mode between each HBQs and DNA was quite complicated, and there were both minor groove binding and intercalation binding. Molecular docking showed that HBQs interacted with DNA predominantly via hydrogen bond at guanine-rich areas in the minor groove of DNA. The genotoxicity of HBQs on human hepatocytes (L-02) was evaluated by micronucleus test, and the results showed that HBQs could cause significant chromosomal damage. The rank order of HBQ isomers on DNA reactivity and genotoxicity was 2,5-HBQs > their corresponding 2,6-HBQs. QSTR analysis found that dipole moment is the key structural descriptor influencing both DNA reactivity and genotoxicity of HBQ isomers. This study suggested that HBQs have caused genotoxicity which was influenced by their isomeric effects, warranting a comprehensive understanding of the genotoxic and carcinogenic risks associated with HBQs exposure.

Synthesis of urchin-like and yolk-shell TiO2 microspheres with enhanced photocatalytic properties.

The novel urchin-like and yolk-shell titania microspheres (henceforth called UYTMs) with nanowires/microspheres hierarchical structures were successfully synthesized by a synthetic sol-gel and hydrothermal method without using any template. Uniform TiO2 microspheres were firstly prepared by the sol-gel method, and the great monodispersed properties was delicately regulated by using the surfactant of KCl, aniline and a proper amount of water. The urchin-like yolk-shell morphology was further achieved by a NaOH-assisted hydrothermal process, and the diameter and shell thickness of the UYTMs were highly controlled by the concentration of NaOH. The detailed morphology, chemical composition and crystallinity of the UYTMs were systematically characterized by several techniques, and the underlying formation mechanisms was attentively discussed as well. The photodegradation of methylthionine chloride experiments indicated the UYTMs showed much better photocatalytic activity than that of commercial P25. This is mainly because the UYTMs exhibited much more reactive sites, higher adsorption ability and tuned optical absorption behaviour owing to their large specific surface area, hierarchical structures and the special hollow yolk-shell structure.