Comparative Proteomics Analysis of Selenium Responses in Selenium-Enriched Rice Grains

By foliar fortification with selenite, selenium (Se)-enriched rice with a higher Se content and grain yield has been generated. However, the regulatory mechanisms of Se response in rice grains remain unknown; therefore, we carried out a comparative proteomics study in Se-enriched rice grains by using two approaches including two-dimensional gel electrophoresis (2-DE)-coupled MALDI-TOF/TOF MS and 1-DE/LC–FTICR–MS-coupled label-free quantification. By comparison between Se treatment and control, 62 and 250 abundance changed proteins were identified from 2-DE and 1-DE, respectively. By functional classification, proteins involved in metabolism, cell redox regulation, and seed nutritional storage were the most highly affected by Se accumulation. The up-regulation of late embryogenesis abundant proteins as well as proteins involved in sucrose synthesis and other metabolism pathways may contribute to the earlier maturation and higher yield of the Se-enriched rice. In addition, there have been six proteins identified to contain selenoamino acid modification, which is the first identification of selenoproteins in higher plants. In conclusion, our study provided novel insights into Se response in rice grains at the proteome level, which are expected to be highly useful for dissecting the Se response pathways in rice and for the production of Se-enriched rice in the future

Directing Group in Decarboxylative Cross-Coupling: Copper-Catalyzed Site-Selective C–N Bond Formation from Nonactivated Aliphatic Carboxylic Acids

Copper-catalyzed directed decarboxylative amination of nonactivated aliphatic carboxylic acids is described. This intramolecular C–N bond formation reaction provides efficient access to the synthesis of pyrrolidine and piperidine derivatives as well as the modification of complex natural products. Moreover, this reaction presents excellent site-selectivity in the C–N bond formation step through the use of directing group. Our work can be considered as a big step toward controllable radical decarboxylative carbon–heteroatom cross-coupling

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data

<div><p>Background</p><p>Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions.</p><p>Methods</p><p>A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable.</p><p>Results</p><p>Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China.</p><p>Conclusion</p><p>Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.</p></div

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data - Fig 2

<p><b>Probability of Cost-effectiveness in A: Treatment-Naïve and B: Treatment-Experienced patients, by economic regions in China.</b> The probability was at the willingness-to-pay of 3 GDP per capita in each region.</p

Model transition probabilities, cost inputs and utilities.

<p>Model transition probabilities, cost inputs and utilities.</p

Simplified Markov Model.

<p>Subjects can progress through fibrosis stages F0-F4, DC based on natural progression rates. Fibrosis regression after SVR is possible for subject in stage F3 and F4. Further fibrosis progression to HCC, liver transplant after SVR is possible for subjects in stages F4 and DC at lower rates. DC, decompensated cirrhosis; F0-F4, Metavir fibrosis stages; HCC, Hepatocellular carcinoma.</p

Prices that make sofosbuvir/ledipasvir cost-effective, by four economic regions in China.

<p>Prices that make sofosbuvir/ledipasvir cost-effective, by four economic regions in China.</p