SummaryThe IKK/NF-kB pathway is an essential signalling process initiated by the cell as a defence against viral infection like influenza virus. This pathway is therefore a prime target for viruses attempting to counteract the host response to infection. Here, we report that the influenza A virus NS1 protein specifically inhibits IKK-mediated NF-kB activation and production of the NF-kB induced antiviral genes by physically interacting with IKK through the C-terminal effector domain. The interaction between NS1 and IKKa/IKKb affects their phosphorylation function in both the cytoplasm and nucleus. In the cytoplasm, NS1 not only blocks IKKb-mediated phosphorylation and degradation of IkBa in the classical pathway but also suppresses IKKa-mediated processing of p100 to p52 in the alternative pathway, which leads to the inhibition of nuclear translocation of NF-kB and the subsequent expression of downstream NF-kB target genes. In the nucleus, NS1 impairs IKKmediated phosphorylation of histone H3 Ser 10 that is critical to induce rapid expression of NF-kB target genes. These results reveal a new mechanism by which influenza A virus NS1 protein counteracts host NF-kB-mediated antiviral response through the disruption of IKK function. In this way, NS1 diminishes antiviral responses to infection and, in turn, enhances viral pathogenesis.

Drug-induced cardiotoxicity seriously affects human health and drug development. However, many conventional detection indicators of cardiotoxicity exhibit significant changes only after the occurrence of severe heart injuries. Therefore, we investigated more sensitive and reliable indicators for the evaluation and prediction of cardiotoxicity. We created rat cardiotoxicity models in which the toxicity was caused by doxorubicin (20 mg/kg), isoproterenol (5 mg/kg), and 5-fluorouracil (125 mg/kg). We collected data from rat plasma samples based on metabolomics using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Following multivariate statistical and integration analyses, we selected 39 biomarker ions of cardiotoxicity that predict cardiotoxicity earlier than biochemical analysis and histopathological assessment. Because drugs with different toxicities may cause similar metabolic changes compared with other noncardiotoxic models (hepatotoxic and nephrotoxic models), we obtained 10 highly specific biomarkers of cardiotoxicity. We subsequently used a support vector machine (SVM) to develop a predictive model to verify and optimize the exclusive biomarkers. l-Carnitine, 19-hydroxydeoxycorticosterone, LPC (14:0), and LPC (20:2) exhibited the strongest specificities. The prediction rate of the SVM model is as high as 90.0%. This research provides a better understanding of drug-induced cardiotoxicity in drug safety evaluations and secondary development and demonstrates novel ideas for verification and optimization of biomarkers via metabolomics.

This manuscript introduces a one-pot fabrication procedure for the preparation of supramolecular hybrid hydrogels from low-cost commercially available natural products through a "green" strategy. In particular, the hybrid hydrogels, which are developed with Fmoc-Glu-OMe, silver nanoparticles and chitosan, exhibit outstanding antibacterial properties and can be regarded as excellent mouldable wound healing biomaterials.

MUC16/CA125 has been identified as a prominent cancer biomarker, especially for epithelial ovarian cancers, in clinical test for over three decades. Due to its huge mass, limited knowledge of MUC16 was acquired previously. By utilizing a well characterized self-made MUC16 monoclonal antibody, we identified the endogenous interaction between a C-terminal fragment of MUC16 (MUC16C) and β-catenin for the first time, and further elucidated that trans-activation domain of β-catenin is required for this interaction. Such interaction could activate the Wnt/β-catenin signaling pathway by facilitating cytosol-nucleus transportation of β-catenin, consequently induce cell proliferation and the migration, eventually lead to tumorigenesis and metastasis in nude mice. Consistently, knockdown of MUC16 significantly weakened the capabilities of cells for proliferation and migration. Based on our discovery, we suggest that MUC16 appears as an attractive target for the development of effective anticancer drugs.

Homeodomain-leucine zipper (HD-Zip) proteins are a kind of transcriptional factors that play a vital role in plant growth and development. However, no detailed information of HD-Zip family in tomato has been reported till now. In this study, 51 HD-Zip genes (SlHZ01-51) in this family were identified and categorized into 4 classes by exon–intron and protein structure in tomato (Solanum lycopersicum) genome. The synthetical phylogenetic tree of tomato, Arabidopsis and rice HD-Zip genes were established for an insight into their evolutionary relationships and putative functions. The results showed that the contribution of segmental duplication was larger than that of tandem duplication for expansion and evolution of genes in this family of tomato. The expression profile results under abiotic stress suggested that all SlHZ I genes were responsive to cold stress. This study will provide a clue for the further investigation of functional identification and the role of tomato HD-Zip I subfamily in plant cold stress responses and developmental events.

Biomass-derived carbon aerogel with hierarchical porosity and FeN4 single atom sites outperforms platinum towards the oxygen reduction reaction in alkaline media and can be used as the cathode catalyst for aluminium–air batteries.

KuDieZi (KDZ) injection is prepared by extracting and processing Ixeris sonchifolia [Ixeris sonchifolia Hance] belonging to Lactuca genus of the Asteraceae family. KDZ injection is a single-herb preparation in which components are analysed by liquid chromatographymass spectrometry. However, the chemical compositions of this preparation are complex and diverse. Hence, data processing is complicated and time consuming; furthermore, data processing can not provide a systematic, accurate and repeatable method to rapidly 10 classify and identify chemical constituents of the injection. In our study, the main components, particularly flavonoids, organic acids, amino acids and nucleosides in KDZ injection, were rapidly classified and identified by data processing technology based on UPLC-Q-TOF/MS. After we reviewed lots of studies and collected the fragments' information, then compared with the mass spectrometric analyses in standards, the rules of diagnostic fragments (DFs) and neutral losses (NLs) of the four substances were established and summarised. A rapid classification and identification method of the chemical compositions of KDZ injection was then constructed using 15 DF filter (DFF) and NL filter (NLF). This method was applied to analyse the KDZ injection. A total of 31 chemical components, which included 8 flavonoids, 13 organic acids, 6 amino acids and 4 nucleosides, were obtained. DFF and NLF were used to rapidly classify and identify chemical substances in KDZ fingerprint. With this method, we effectively solved the technical difficulties in fingerprint resolution caused by complex components and low levels in traditional Chinese medicine (TCM). In addition, this study provided a novel approach for further studies on TCM.

This paper introduces a new metallohydrogel precursor that offers a peculiar gelation response to Co(2+) at pH 7-8. It is notable that the stability of this metallohydrogel is significantly dependent on its enantiomeric purity. In addition to the expected multi-stimuli responsive properties, including thixotropy, as well as re-assembly properties on adding HCl, this metallohydrogel possesses excellent self-healing behavior, which is uncommon in low-molecular-weight gelators. Electron microscopy (EM) studies revealed that the cryodried remains of this gel presented as well an organized three dimensional (3D) network of fibrils. This interesting metallohydrogel shows potential for developing new soft materials with drug delivery and catalysis properties.