No abstract

Viral infection activates transcription factors, such as NF-κB and IFN regulatory factor 3, which collaborate to induce type I IFNs and elicit innate antiviral response. Virus-induced signaling adaptor (VISA) has been identified as a critical adaptor required for virus-triggered induction of type I IFNs. In this study, we showed that the E3 ubiquitin ligase RING-finger protein 5 (RNF5) interacted with VISA at mitochondria in a viral infection-dependent manner. Domain mapping experiments indicated that the C-terminal transmembrane domain of VISA was required for its interaction with RNF5. RNF5 targeted VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection, whereas knockdown of RNF5 reversed virus-induced downregulation of VISA at the early phase. These findings suggest that RNF5-mediated ubiquitination and degradation of VISA is one of the mechanisms of the regulation of virus-triggered induction of type I IFNs and cellular antiviral response.

In clinical practice, it is difficult to identify tumor margins during brain surgery due to its inherent infiltrative character. Herein, a unique dual-modality nanoprobe (Gd-DOTA-Ag2S QDs, referred as Gd-Ag2S nanoprobe) is reported, which integrates advantages of the deep tissue penetration of enhanced magnetic resonance (MR) imaging of Gd and the high signal-to-noise ratio and high spatiotemporal resolution of fluorescence imaging in the second near-infrared window (NIR-II) of Ag2S quantum dots (QDs). Due to the abundant tumor angiogenesis and the enhanced permeability and retention effect in the tumor, a brain tumor (U87MG) in a mouse model is clearly delineated in situ with the help of the Gd assisted T1 MR imaging and the intraoperative resection of the tumor is precisely accomplished under the guidance of NIR-II fluorescence imaging of Ag2S QDs after intravenous injection of Gd-Ag2S nanoprobe. Additionally, no histologic changes are observed in the main organs of the mouse after administration of Gd-Ag2S nanoprobe for 1 month, indicating the high biocompatibility of the nanoprobe. We expect that such a novel "Detection and Operation" strategy based on Gd-Ag2S nanoprobe is promising in future clinical applications.

Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.

The creation of pH responsive materials that undergo morphological transitions between micelle and vesicle induced by solution pH change is of great importance for their potential application in drug delivery and biochemical engineering. Here, we have developed a series of 18 pH responsive ionic liquids composed of 1-alkyl-3-methylimidazolium cation, [C(n)mim](+) (n = 4, 6, 8, 10, 12, 14), and different pH responsive anions such as potassium phthalic acid ([C6H4COOKCOO](-)), sodium sulfosalicylic acid ([C6H3OHCOOSO3Na](-)), and sodium m-carboxylbenzenesulfonate ([C6H4COOSO3Na](-)). The aggregation behavior and self-assembly structures of the ILs in aqueous solution have been investigated by surface tension, dynamic light scattering, transmission electron microscopy, small-angle X-ray scattering, and nuclear magnetic resonance spectroscopy. It was found for the first time that single tail ionic liquids, [C(n)mim]X (n = 12 and 14, X = [C6H4COOKCOO], [C6H3OHCOOSO3Na], and [C6H4COOSO3Na]) could form vesicles without any additives, and reversible transition was observed between spherical micelles and vesicles with the change of solution pH value. The transition in self-assembly structures is suggested to be driven by the variation in molecular structure and hydrophilicity/hydrophobicity of anions of the ILs.

Aims. To examine whether hydrogen sulfide (H2S) generation changed in ageing diabetic mouse hearts. Results. Compared to mice that were fed tap water only, mice that were fed 30% fructose solution for 15 months exhibited typical characteristics of a severe diabetic phenotype with cardiac hypertrophy, fibrosis, and dysfunction. H2S levels in plasma, heart tissues, and urine were significantly reduced in these mice as compared to those in controls. The expression of the H2S-generating enzymes, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase, was significantly decreased in the hearts of fructose-fed mice, whereas cystathionine-β-synthase levels were significantly increased. Conclusion. Our results suggest that this ageing diabetic mouse model developed diabetic cardiomyopathy and that H2S levels were reduced in the diabetic heart due to alterations in three H2S-producing enzymes, which may be involved in the pathogenesis of diabetic cardiomyopathy.

No abstract

No abstract