Search

With the increasing number of patients waiting for liver transplantation, donor shortage has become a serious problem. The use of grafts from marginal donors and donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. The benefits of hypothermic oxygenated machine perfusion (HOPE) in many clinical trials have been reported. On the other hand, normothermic machine perfusion (NMP) has been also performed and demonstrated to improve graft function. The application of preservation solution with artificial oxygen carrier solution under subnormothermic machine perfusion for marginal liver graft was shown. Furthermore, long-term maintaining of graft function or recovery by NMP enables ex vivo cell and gene therapy. Thus, machine perfusion technology may alleviate the not only preservation of marginal graft but also new ex vivo bioengineering. [ABSTRACT FROM AUTHOR]

A reductive (3+2) annulation of lactams through iridium‐catalyzed hydrosilylation and photoredox coupling with α‐bromoacetic acid was developed. The iridium‐catalyzed hydrosilylation of the lactam carbonyl group and subsequent elimination provide a transient cyclic enamine, which undergoes iridium‐catalyzed photoredox coupling with α‐bromoacetic acid in a one‐pot process. The developed conditions show high functional‐group tolerance and provide cyclic N,O‐acetals containing a quaternary carbon center. The resulting N,O‐acetals undergo a variety of acid‐mediated nucleophilic addition reactions via iminium ions to give substituted cyclic amines. The developed sequence including reductive (3+2) annulation and acid‐mediated nucleophilic addition was successfully applied to the four‐step total synthesis of (±)‐eburnamonine. [ABSTRACT FROM AUTHOR]

We propose a hybrid seesaw model based on |$A_{4}$| flavor symmetry, which generates a large hierarchical flavor structure. In our model, tree-level and one-loop seesaw mechanisms predict different flavor structures in the neutrino mass matrix and generate a notable hierarchy among them. We find that such a hierarchical structure gives a large effective neutrino mass that can be accessible by next-generation neutrinoless double beta decay experiments. Majorana phases can also be predictable. The |$A_{4}$| flavor symmetry in the model is spontaneously broken to the |$Z_{2}$| symmetry, leading to a dark matter candidate that is assumed to be a neutral scalar field. The favored mass region of the dark matter is obtained by numerical computations of the relic abundance and the cross section of the nucleon. We also investigate the predictions of several hierarchical flavor structures based on |$A_{4}$| symmetry for the effective neutrino mass and the Majorana phases, and find characteristic features depending on the hierarchical structures. [ABSTRACT FROM AUTHOR]

FSK0808 is a recombinant human granulocyte colony-stimulating factor developed by Fuji Pharma Co., Ltd and Mochida Pharmaceutical Co., Ltd. as a biosimilar product of Gran®. We verified the pharmacokinetic/pharmacodynamic equivalence of FSK0808 and commercially available Gran® by a randomized crossover study of single intravenous dose (200 µg/m2) and single subcutaneous dose (400 µg/m2) in healthy Japanese adult male subjects. According to the bioequivalence guidelines, the area under the blood concentration - time curve by 48 hours after administration (AUC0-48) in a single intravenous drip (IVD) study, and AUC0-48 and maximum blood concentration ( Cmax) in a single subcutaneous (SC) dose study were used as primary endpoints, and the pharmacodynamic parameters including absolute neutrophil count (ANC) or number of CD34 positive cells (CD34+ cells) as secondary endpoints. The safety was evaluated based on the characteristics and incidence of adverse reactions. As a result, the 90% confidence interval (CI) of the difference in mean value for AUC0-48 among drugs ranged from log(0.8) to log(1.25), in the IVD study, and those for Cmax and AUC0-48 were within the range of log(0.8)-log(1.25) in the SC study. Those for secondary endpoints were all within the range of log(0.8)-log(1.25). Thus, the pharmacokinetics/pharmacodynamics of both drugs were considered equivalent for all routes of administration, and the profiles of adverse reactions were also very similar. [ABSTRACT FROM AUTHOR]