Objective To compare the efficacy and safety of tenofovir disoproxil fumarate ( TDF) and entecavir(ETV) in the treatment of chronic hepatitis B(CHB) with positive hepatitis B E antigen(HBeAg). Methods A total of 104 cases with newly diagnosed HBeAg positive CHB were selected and randomly divided into TDF group and ETV group,with 52 cases in each group. The TDF group was given 300mg/d TDF,and the ETV group was given 0. 5mg/d ETV. All the patients were continuously treated for 12 months. The serum HBV DNA, HBeAg and ALT levels before and after treatment were compared between the two groups. Results Before treatment,there were no statistically significant differences in serum HBV DNA,HBeAg and ALT levels between the two groups ( t=0. 12, 1. 51,1. 62,all P＞0. 05). The serum HBV DNA,HBeAg and ALT levels in the two groups were decreased after treatment,and the decrease of serum HBV DNA level in the TDF group was more significant than that in the ETV group,the difference was statistically significant(t =3. 54,P ＜0. 05),but there were no statistically significant differences in serum HBeAg and ALT levels between the two groups(t=0. 04,0. 79,all P＞0. 05). The total effective rate of the TDF group was 92. 31% (48/52),which was significantly higher than 76. 92% (40/52) in the ETV group (χ2=4. 73,P＜0. 05). During treatment,the incidence rate of adverse reaction of the TDF group was 7. 69% (4/52),which was lower than 11. 54% (6/52) of the ETV group,but the difference was not statistically significant (χ2=0. 44,P＞0. 05). Conclusion TDF has better clinical effect in treating newly diagnosed HBeAg positive CHB than ETV due to TDF can inhibit HBV DNA replication significantly,but the safety of TDF and ETV is similar.

Effective utilization of xylose is a basis for economic production of biofuels or chemicals from lignocellulose biomass. Over the past 30 years, through metabolic engineering, evolutionary engineering and other strategies, the metabolic capacity of xylose of the traditional ethanol-producing microorganism Saccharomyces cerevisiae has been significantly improved. In recent years, the reported results showed that the transcriptome and metabolome profiles between xylose and glucose metabolism existed significant difference in recombinant yeast strains. Compared with glucose, the overall process of xylose metabolism exhibits Crabtree-negative characteristics, including the limited glycolytic pathway activity, which reduces the metabolic flux of pyruvate to ethanol, and the enhanced cytosolic acetyl-CoA synthesis and respiratory energy metabolism. These traits are helpful to achieve efficient synthesis of downstream products using pyruvate or acetyl-CoA as precursors. This review provides a detailed overview on the modification and optimization of xylose metabolic pathways in S. cerevisiae, the characteristics of xylose metabolism, and the construction of cell factories for production of chemicals using xylose as a carbon source. Meanwhile, the existed difficulties and challenges, and future studies on biosynthesis of bulk chemicals using xylose as an important carbon source are proposed.
Biofuels ; Ethanol ; Fermentation ; Metabolic Engineering ; Saccharomyces cerevisiae/genetics* ; Xylose

As a generally-recognized-as-safe microorganism, Saccharomyces cerevisiae is a widely studied chassis cell for the production of high-value or bulk chemicals in the field of synthetic biology. In recent years, a large number of synthesis pathways of chemicals have been established and optimized in S. cerevisiae by various metabolic engineering strategies, and the production of some chemicals have shown the potential of commercialization. As a eukaryote, S. cerevisiae has a complete inner membrane system and complex organelle compartments, and these compartments generally have higher concentrations of the precursor substrates (such as acetyl-CoA in mitochondria), or have sufficient enzymes, cofactors and energy which are required for the synthesis of some chemicals. These features may provide a more suitable physical and chemical environment for the biosynthesis of the targeted chemicals. However, the structural features of different organelles hinder the synthesis of specific chemicals. In order to ameliorate the efficiency of product biosynthesis, researchers have carried out a number of targeted modifications to the organelles grounded on an in-depth analysis of the characteristics of different organelles and the suitability of the production of target chemicals biosynthesis pathway to the organelles. In this review, the reconstruction and optimization of the biosynthesis pathways for production of chemicals by organelle mitochondria, peroxisome, golgi apparatus, endoplasmic reticulum, lipid droplets and vacuole compartmentalization in S. cerevisiae are reviewed in-depth. Current difficulties, challenges and future perspectives are highlighted.
Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism* ; Golgi Apparatus/metabolism* ; Metabolic Engineering ; Vacuoles/metabolism*