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Objective: Optically active (R)-ethyl 4-chloro-3-hydroxybutyrate ((R)-CHBE) is a useful chiral building block for the synthesis of pharmaceuticals. Recently, there has been great interest in the synthesis of (R)-CHBE via the highly stereoselective bioreduction of ethyl 4-chloro-3-oxobutanoate (COBE) under mild conditions. Methods: A highly efficient bioreduction process for transforming COBE into (R)-CHBE was developed in a biocompatible organic solvent–deep eutectic solvent–water reaction medium. Results: Recombinant Escherichia coli containing carbonyl reductase (CgCR) and glucose dehydrogenase (GDH) was successfully constructed and characterized. In addition, the feasibility of the asymmetric bioreduction of COBE to (R)-CHBE was verified in an organic solvent–deep eutectic solvent–water (ethyl acetate-betaine/lactic acid-water) system. At pH 7.0 and 30 °C, the kinetic constants Km and kcat of COBE were 20.9 mM and 56.1 s−1, respectively. A high (R)-CHBE yield (≥90%) was achieved by catalyzing COBE (1000 mM) in 12 h with E. coli CgCR cells in the presence of Ni2+ (7 mM) and glucose (3.5 mM glucose/mM COBE) in an ethyl acetate-betaine/lactic acid-H2O (50/7/43, v/v/v) system. The effects of organic solvents and DESs on whole-cell permeability were analyzed. Conclusions: An efficient bioreduction system was constructed for biologically transforming COBE to (R)-CHBE via whole-cell biocatalysis, and the established bioprocess has potential application in future. [ABSTRACT FROM AUTHOR]

The afterglow data of gamma ray bursts (GRBs) can be used to constrain the physical properties of the fireball (e.g., the jet structure and opening angle) and the circumburst medium. With the peak time of the early afterglow light curve being taken as the deceleration time, one can estimate the initial Lorentz factor of the fireball. In this work, we perform a comprehensive analysis on the prompt emission and the afterglow data of GRB 181110A, where a clear peak is detected by Swift UVOT and XRT in optical to X-ray bands. Prompt emission spectral analysis shows that the spectrum of GRB 181110A is soft, and both hard-to-soft and intensity-tracking spectral evolution are found. By fitting the afterglow light curve and building spectral energy distribution, we find that the standard external forward shock model with a constant circumburst medium is favored, and the jet structure of GRB 181110A tends to be uniform rather than structured. With the peak time of early afterglow emission, we estimate the initial fireball Lorentz factor of GRB 181110A to be Γ 0 = 169 − 40 + 92 . We also compare GRB 181110A with other typical long GRBs in a statistical context. [ABSTRACT FROM AUTHOR]

Our previous study showed that glycyrrhizin (GLY) inhibited porcine epidemic diarrhea virus (PEDV) infection, but the mechanisms of GLY anti-PEDV action remain unclear. In this study, we focused on the anti-PEDV and anti-proinflammatory cytokine secretion mechanisms of GLY. We found that PEDV infection had no effect on toll-like receptor 4 (TLR4) protein and mRNA levels, but that TLR4 regulated PEDV infection and the mRNA levels of proinflammatory cytokines. In addition, we demonstrated that TLR4 regulated p38 phosphorylation but not extracellular regulated protein kinases1/2 (Erk1/2) and c-Jun N-terminal kinases (JNK) phosphorylation, and that GLY inhibited p38 phosphorylation but not Erk1/2 and JNK phosphorylation. Therefore, we further explored the relationship between high mobility group box-1 (HMGB1) and p38. We demonstrated that inhibition of HMGB1 using an antibody, mutation, or knockdown decreased p38 phosphorylation. Thus, HMGB1 participated in activation of p38 through TLR4. Collectively, our data indicated that GLY inhibited PEDV infection and decreased proinflammatory cytokine secretion via the HMGB1/TLR4-mitogen-activated protein kinase (MAPK) p38 pathway.