Sequence analysis-based characterization and identification of neurovirulence-associated variants of 36 EV71 strains from China.

Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and causes several neurological complications. As new strains of EV71 are constantly discovered, it is important to understand the genomic characteristics of the viruses and the mechanism of virulence. Herein, we isolated five strains of EV71 from HFMD patients with or without neurovirulence and sequenced their whole genomes. We then performed whole genome sequence analysis of totally 36 EV71 strains. The phylogenetic analysis of the VP1 region revealed all five isolated strains are clustered into C4a of C4 subgenotype. In addition, by comparing the complete genome sequences of 36 strains, 253 variable amino acid positions were found, 14 of which were identified to be associated with neurovirulence (P < 0.05). Moreover, a similar pattern of amino acid variants combination was identified in four strains without neurovirulence, indicating this type of variant pattern might be associated with avirulence. The strains with neurovirulence appeared to be distinguished from those without neurovirulence by the variants in VP1 and P2 regions, implying VP1 and P2 are the important regions associated with neurovirulence. Indeed, 3-D modeling of VP1 and P2 regions of non-neurovirulent and neurovirulent strains revealed that the different variants resulted in different protein structures and amino acid composition of ligand binding site, which might account for their difference in neurovirulence. In summary, our study reveals 14 variable amino acid positions of VP1, P2 and P3 regions are related to the virulence and that mutations in the capsid proteins of EV71 might contribute to neurovirulence.

In-situ formed nanoscale Fe0 for fenton-like oxidation of thermosetting unsaturated polyester resin composites: Nondestructively recycle carbon fiber.

Thermosetting unsaturated polyester resin (UPR) composites were found widespread industrial applications. However, the numerous stable carbon-carbon bonds in cross-linked networks made them intractable for degradation, causing the large-scale composite wastes. Here a nanoscale Fe0 catalyst in-situ forming strategy was exploited to nondestructively recycle carbon fiber (CF) from UPR composites via Fenton-like reaction. The nano-Fe0 catalyst employed in this strategy activated H2O2 for removing UPR, featuring mild conditions and efficient degradation ability. Aiming at facile growth of the catalyst, a porous UPR was achieved by the hydrolysis of alkalic system. The nanoscale Fe0 catalyst was subsequently formed in-situ on the surface of hydrolyzed resin by borohydride reduction. Benefiting from fast mass transfer, the in-situ grown nano-Fe0 showed more efficient degradation ability than added nano-Fe0 or Fe2+ catalyst during Fenton-like reaction. The experiments indicated that hydrolyzed resin could be degraded more than 90% within 80 min, 80 °C. GC-MS, FT-IR analysis and Density functional theory (DFT) calculation were conducted to explained the fracture processes of carbon skeleton in hydrolyzed resin. Especially, a remarkable recovery process of CF from composites was observed, with a 100 percent elimination of resin. The recycled CF cloth exhibited a 99% strength retention and maintained the textile structure, microtopography, chemical structure, resulting in the nondestructive reclaim of CF. This in-situ formed nanoscale Fe0 catalytic degradation strategy may provide a promising practical application for nondestructively recycle CF from UPR composites.

Combination of apolipoprotein A1-modi liposome-doxorubicin with autophagy inhibitors overcame drug resistance in vitro.

Multidrug resistance (MDR) represents the major drawback in chemotherapy. Liposome-based approaches could reverse MDR to some extent through circumventing the active efflux effect of P-glycoprotein. However, the reverse power of liposome is very limited because the nontargeting liposome is inefficient to deliver drugs to tumor actively. Besides, autophagy could reinforce the resistance of tumor cells to the cytotoxicity of intracellular drugs. Here, liposomal doxorubicin (Lipodox) that was conjugated with apolipoprotein A1-apo-Lipodox, was employed in tumor targeting delivery of doxorubicin. In the experiments, apo-Lipodox could enter cells effectively and reverse MDR more efficiently than their nontargeting counterpart. Autophagy occurred in this process and contributed to the survival of tumor cells. Combination use of autophagy inhibitors could enhance the cytotoxicity of apo-Lipodox and reverse drug resistance to a higher degree. We propose that this strategy holds promise to overcome MDR in human cancer.

Delivery of hydrophilic drug doxorubicin hydrochloride-targeted liver using apoAI as carrier.

High-density lipoprotein (HDL) particles can deliver cholesterol from peripheral tissues to the liver through apolipoprotein A1 (Apo A1), which specifically binds to the scavenger receptor class B type 1 (SR-B1) receptor on the surface of hepatocytes. Therefore, ApoA1 can be potentially used to target drugs to the liver. In this study, we successfully loaded doxorubicin hydrochloride (Dox or Dox-HCl), which is a hydrophilic drug used in a wide variety of clinical applications, into the core of reconstituted HDL (rHDL prepared by apoAI and egg phospholipids) to form a doxorubicin-HDL complex (rHDL-Dox). The MTT assays showed that rHDL-Dox particles also had higher cytotoxicity against several cells lines compared to free drug or Dox encapsulated into liposomes. A cellular uptake assay demonstrated that rHDL-Dox had higher absorption in SR-BI receptor positive liver cells. Importantly, in vivo experiments showed that rHDL-Dox can reduce tumor growth more effectively than liposomes. In addition, an in vitro hemolysis assay showed that rHDL-Dox caused only limited hemolysis in the case of high doses. Taken together, our findings indicate that rHDL is a safe and effective drug delivery system for targeting liver.