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The mechanosensitive ion channel of large conductance (MscL) is a promising template for the development of new antibiotics due to its high conservation and uniqueness to microbes. Brilliant green (BG), a triarylmethane dye, has been identified as a new antibiotic targeted MscL. However, the detailed binding sites to MscL and the dynamic pathway of BG through the MscL channel remain unknown. Here, the dynamic interactions between BG and MscL were investigated using solid-state NMR spectroscopy and molecule dynamics (MD) simulations. Residue site-specific binding sites of BG to the MscL channel were identified by solid-state NMR. In addition, MD simulations revealed that BG conducts through the MscL channel via residues along the inner surface of the pore sequentially, in which the strong hydrophobic interactions between BG and hydrophobic residues F23 and I27 in the hydrophobic gate region of the MscL channel are major restrictions. Particularly, it was demonstrated that BG activates the MscL channel by reducing the hydrophobicity of the F23 in the gate region by water molecules that are bound to BG. Taken together, these simulations and experimental data provide novel insights into the dynamic interactions between BG and MscL, based on which new hydrophobic antibiotics and adjuvants targeting MscL can be developed., (© 2022 Wiley-VCH GmbH.)

A joint experimental and computational study on the glucose-fructose conversion in water is reported. The reactivity of different metal catalysts (CrCl3, AlCl3, CuCl2, FeCl3, and MgCl2) was analyzed. Experimentally, CrCl3 and AlCl3 achieved the best glucose conversion rates, CuCl2 and FeCl3 were only mediocre catalysts, and MgCl2 was inactive. To explain these differences in reactivity, DFT calculations were performed for various metal complexes. The computed mechanism consists of two proton transfers and a hydrogen-atom transfer; the latter was the rate-determining step for all catalysts. The computational results were consistent with the experimental findings and rationalized the observed differences in the behavior of the metal catalysts. To be an efficient catalyst, a metal complex should satisfy the following criteria: moderate Brønsted and Lewis acidity (pKa = 4-6), coordination with either water or weaker σ donors, energetically low-lying unoccupied orbitals, compact transition-state structures, and the ability for complexation of glucose. Thus, the reactivity of the metal catalysts in water is governed by many factors, not just the Lewis acidity., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To evaluate the potential risk of porcine endogenous retrovirus (PERV) cross-species transmission xenotransplanted with microencapsulated neonatal pig islets (NPIs)., Methods: Ten dogs were randomly divided into an experiment group and a control group. The experiment group was transplanted with microencapsulated NPIs, and the control group was transplanted with non-microencapsulated NPIs. Glucose tolerance test (GTT) was performed to evaluate the function of microencapsulated NPIs after the transplantation; immunity histochemistry was used to detect the microencapsulated NPIs in the liver of dogs which had been transplanted after 28 days; PCR and RT-PCR were performed to detect PERV and pig mitochondrial (mt) DNA in the blood samples obtained from recipients at various time points after the transplantation., Results: The level of serum special porcine C peptide increased significantly after the injection of glucose for 15 approximately 30 min in dogs which were transplanted with the micro-encapsulated NPIs over 2 weeks, while special porcine C peptide could not be detected in the control group. Immunity histochemistry showed that a few microencapsulated NPIs were still alive in the liver of the dog, and the liver was not damaged. PCR and RT-PCR showed that pig mt DNA and PERV could not be detected in the experiment group 1 approximately 28 days after the transplantation, while very weak expression of that in the control could be detected in the first 4 days and disappeared 10 days after the transplantation., Conclusion: Microencapsulated NPIs can survive and have biological function in dogs. There is no evidence of PERV replication, suggesting that the xenotransplantation with microencapsulated NPIs can prevent PERV effectively, and may have great value.