Discovery of novel pyrrolo[2,1-c][1,4]benzodiazepine-3,11-dione (PBD) derivatives as selective HDAC6 inhibitors for the efficient treatment of idiopathic pulmonary fibrosis (IPF) in vitro and in vivo.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive fibrotic phenotype. Immunohistochemical studies on HDAC6 overexpression in IPF lung tissues confirmed that IPF is associated with aberrant HDAC6 activity. We herein developed a series of novel HDAC6 inhibitors that can be used as potential pharmacological tools for IPF treatment. The best-performing derivative H10 showed good selectivity for multiple isoforms of the HDAC family. The structural analysis and structure-activity relationship studies of H10 will contribute to optimizing the binding mode of the new molecules. The pharmacological mechanism of H10 to inhibit pulmonary fibrosis was validated, and its ability to inhibit the IPF phenotype was also demonstrated. Moreover, H10 showed satisfactory metabolic stability. The efficacy of H10 was also determined in a mouse model of bleomycin-induced pulmonary fibrosis. The results highlighted in this paper may provide a reference for the identification of new drug molecules for the treatment of IPF.

Novel carboxylated cellulose nanocrystals synthesized by co-oxidation of sodium periodate/Fenton as a green solid emulsifier for oil-in-water Pickering emulsion.

The preparation of carboxylated cellulose nanocrystals (cCNCs) and their stabilization in oil-in-water (O/W) Pickering emulsions hold great potential for application and research value. In this work, a novel integrated oxidation strategy was proposed to prepare needle-like cCNCs by sodium periodate (NaIO4)/Fenton (SF-cCNCs) with considerable yield (58.58 %), plentiful carboxyl groups (1.28 mmol/g), and high crystallinity (83.3 %). The distinctive features of smaller size and high viscosity accelerated the as-prepared SF-cCNCs to be used in stabilizing Pickering emulsion. Moreover, the effects of oil-water ratio (OWR), SF-cCNCs content, pH, and sodium chloride (NaCl) content on the stability of SF-cCNCs-stabilized Pickering emulsions were also investigated systematically. Interestingly, the stability of the as-obtained emulsions was dependent on pH and salt. Afterwards, the rheological behaviors validated that the emulsion viscosity increased rapidly after adding NaCl, which was dominated by the elastic behavior. Finally, the main stabilization mechanism was confirmed to be interfacial adsorption of SF-cCNCs rather than the formation of spatial network structures between droplets. This study reports a synthetic strategy to efficiently prepare SF-cCNCs, endowing the SF-cCNCs stabilized Pickering emulsion with environmentally friendly, long-term stable and highly anti-agglomeration abilities for cosmetics and food products.

Pregnancy serum facilitates hepatitis E virus replication in vitro.

Hepatitis E virus (HEV) infection causes high mortality in pregnant women. However, the pathogenic mechanisms of HEV infection in pregnant women remain unknown. In this study, the roles of pregnancy serum in HEV infection were investigated using an efficient cell culture system. HEV infection was exacerbated by supplementing with pregnancy serum, especially theat in third trimester of pregnancy. Oestrogen receptors (ER-α and ER-ß) were activated in cells supplemented with pregnancy serum and were significantly inhibited during HEV infection. Type I IFN, especially IFN-ß, showed delayed upregulation in HEV-infected cells supplemented with the serum in the third trimester of pregnancy, which indicated that delayed IFN-ß expression may facilitate viral replication. Results suggested that pregnancy serum accelerated HEV replication by suppressing oestrogen receptors and type I IFN in the early stage of infection.

Complete genome sequence of Swine hepatitis e virus prevalent in southwest china.

Hepatitis E virus (HEV) is an important public health concern in the world, especially in developing countries of Africa and Asia, including China. Hepatitis E is recognized as a zoonotic disease, which is transmitted across species, including between humans and swine. HEV is highly endemic in China, but the complete sequence of HEV in southwestern China is lacking. Swine HEV strain KM01 was isolated from a village in rural Kunming, Yunnan province, China, where swine are housed with humans. Here, we report the complete genome sequence of the swine HEV strain KM01. The sequence and phylogenetic analyses reveal that swine HEV is closely related to the strain isolated from Xinjiang (CHN-XJ-SW13). The genome of the KM01 strain will facilitate further study of HEV molecular epidemiology and genetic diversity in China.