Synthesis of pH-responsive chitosan nanocapsules for the controlled delivery of doxorubicin.

Well-defined chitosan nanocapsules (CSNCs) with tunable sizes were synthesized through the interfacial cross-linking of N-maleoyl-functionalized chitosan (MCS) in miniemulsions, and their application in the delivery of doxorubicin (Dox) was investigated. MCS was prepared by the amidation reaction of CS with maleic anhydride in water/DMSO at 65 °C for 20 h. Subsequently, thiol-ene cross-linking was conducted in oil-in-water miniemulsions at room temperature under UV irradiation for 1 h, using MCS as both a surfactant and precursor polymer, 1,4-butanediol bis(3-mercapto-propionate) as a cross-linker, and D-α-tocopheryl poly(ethylene glycol) 1000 succinate as a cosurfactant. With the increase in cosurfactant concentration in the reaction systems, the sizes of the resulting CSNCs decreased steadily. Dox-loaded CSNCs were readily prepared by in situ encapsulation of Dox during miniemulsion cross-linking. With acid-labile ß-thiopropionate cross-linkages, the Dox-loaded CSNCs demonstrated a faster release rate under acidic conditions. Relative to free Dox, Dox-loaded CSNCs exhibited enhanced cytotoxicity toward MCF-7 breast cancer cells without any noticeable cytotoxicity from empty CSNCs. The effective delivery of Dox to MCF-7 breast cancer cells via Dox-loaded CSNCs was also observed.

Natural variant R246K in hemagglutinin increased zoonotic characteristics and renal inflammation in mice infected with H9N2 influenza virus.

Considered a potential pandemic candidate, the widespread among poultry of H9N2 avian influenza viruses across Asia and North Africa pose an increasing threat to poultry and human health. The massive epidemic of H9N2 viruses has expanded the host range; however, the molecular basis and characteristic underlying the transmission to poultry and mammals remains unclear. Our previous study has proved that some natural mutations in the HA gene enhanced the binding ability of the H9N2 virus to α-2,6 SA receptors. Here, we systematically analyzed the impact of these natural mutations on zoonotic characteristics and the pathogenicity of H9N2 AIVs in poultry and mammals. Our study demonstrated that mutation R246K increased the replication in human lung epithelial cells in vitro. Mutation R246K increased the virus shedding of oropharyngeal swabs during early-stage infection in chickens. Moreover, mutation R246K displayed stronger pH stability and pathogenicity in mice. The strong renal tropism and inflammatory response may accelerate the pathogenicity. In summary, we found that natural variation R246K in HA of prevalent H9N2 in China promoted the transmissibility in chicken and accelerate the pathogenicity in mice, posing a great concern for zoonotic and pandemic emergence.

Association between HULC rs7763881 and cancer risk: an updated Meta-analysis.

In recent years, several case-control studies have explored the association between the rs7763881 locus polymorphism of the HULC gene and cancer risk, however, the findings have been inconsistent. Therefore, a meta-analysis was conducted to clarify the association. Relevant case-control studies were obtained from CNKI, Embase, Web of Science and PubMed databases. RevMan software was used to perform data analysis. A total of 8 case-control studies containing 4036 cases and 5286 controls were included in the current meta-analysis. The overall analysis results showed no significant association between the rs7763881 locus polymorphism and cancer risk. However, stratified analysis based on cancer type showed that the rs7763881 locus polymorphism was associated with the decreased risk of hepatocellular cancer, colorectal cancer and esophageal cancer. In conclusion, the current findings suggest that the rs7763881 polymorphic loci located on the HULC gene may serve as a biomarker for determining an individual's risk of hepatocellular cancer, colorectal cancer and esophageal cancer.

The first complete genome sequence and pathogenicity characterization of fowl adenovirus serotype 2 with inclusion body hepatitis and hydropericardium in China.

Since 2015, fowl adenovirus (FAdV) has been frequently reported worldwide, causing serious economic losses to the poultry industry. In this study, a FAdV-2, namely GX01, was isolated from liver samples of chickens with hepatitis and hydropericardium in Guangxi Province, China. The complete genome sequence of GX01 was determined about 43,663 base pairs (bp) with 53% G+C content. To our knowledge, this is the first FAdV-2 complete genome in China. There was a deleting fragment in ORF25 gene. Phylogenetic analysis based on the hexon loop-1 gene showed that GX01 is most closely related to FAdV-2 strain 685. Pathogenicity experiment of GX01 in 3-day-old and 10-day-old specific-pathogen-free chickens showed that although no mortality was observed within 21 days post infection (dpi), strain GX01 significantly inhibited weight gain of infected chickens. Moreover, FAdV-2 was still detectable in the anal swabs of infected chickens at 21 dpi. Necropsy analysis showed that the main lesions were observed in liver, heart, and spleen. Of note, hepatitis and hydropericardium were observed in the infected chickens. In addition, massive necrosis of lymphocyte was observed in spleen of infected 3-days-old chickens. We concluded that FAdV-2 strain GX01 is capable of causing hepatitis and hydropericardium, which will make serious impact on the growth of chickens. Our research lays a foundation to investigate the molecular epidemiology and etiology of FAdV.