New strategies to treat antibiotic-resistant infections are urgently needed. We serendipitously discovered that stem cell conditioned media possessed broad antimicrobial properties. Biochemical, functional, and genetic assays confirmed that the antimicrobial effect was mediated by supra-physiological concentrations of transferrin. Human transferrin inhibited growth of gram-positive (Staphylococcus aureus), gram-negative (Acinetobacter baumannii), and fungal (Candida albicans) pathogens by sequestering iron and disrupting membrane potential. Serial passage in subtherapeutic transferrin concentrations resulted in no emergence of resistance. Infected mice treated with intravenous human transferrin had improved survival and reduced microbial burden. Finally, adjunctive transferrin reduced the emergence of rifampin-resistant mutants of S. aureus in infected mice treated with rifampin. Transferrin is a promising, novel antimicrobial agent that merits clinical investigation. These results provide proof of principle that bacterial infections can be treated in vivo by attacking host targets (ie, trace metal availability) rather than microbial targets.
Using non-resonant second harmonic generation (SHG) and heterodyne-detected SHG (HD-SHG) spectra,we studied the broadening mechanism of the electrochemical stability window (ESW) for the super-concentrated LiNO3 aqueous electrolyte. We first investigated the electric double layer structure at the air/LiNO3 interface. As the concentration of LiNO3 increased, the SHG intensity first increased and then remained unchanged, while the SHG phase changed by about 5{degree sign}. These results reveal that there was only a small amount of NO3− at the interface. The increase of SHG intensity resulted from the thickening of the interfacial water molecular layer. We then studied the mechanism of the ESW. During cyclic voltammetry scanning, the potential-dependent SHG curves of the Pt/LiNO3 interface verify that at the cathodic end of the ESW, as the concentration of LiNO3 increased, the orientation angle θ of Pt-H changed less and the number density Ns of Pt-H gradually decreased, which indicates the decrease of the number of adsorbed H atoms on the Pt electrode surface. The conclusion is that the decrease in the number of free water molecules on the Pt electrode surface results in an expanded ESW.
We performed real-time second harmonic generation (SHG) to study the cooperative action of laser-induced thermal effects and ionic coordination on the order/disorder of TPPA0 (5,10,15,20-(tetrakis((ethoxycarbonyl)methoxy)phenyl)porphyrin) monolayers on the interface of three aqueous solutions. Time dependence curves of SH signals of TPPA0 monolayers on pure water and ZnCl 2 aqueous and CuCl 2 aqueous interfaces were detected under the polarization combinations of p-in/p-out, s-in/p-out and 45°-in/s-out. All the SH signals changed with time at the beginning and then reached the equilibrium state. For the pure water and ZnCl 2 aqueous interfaces, SH signals under the polarization of p-in/pout declined with time; while on the CuCl 2 aqueous interfaces, the SH signals raised with time. To explain the various change of the SH signals with time, we also measured these time dependence curves under the polarizations of the p-in/p-out, s-in/p-out, and 45°-in/s-out, all of which can be used to determine the orientation angle and corresponding orientation distribution width. It is found that the orientation angle with δ distribution cannot explain the ratios of the SH signal change; thus, the gauss orientational distribution width has to be considered instead of δ distribution, which means the TPPA0 monolayers undergone the change process of the orientational order until reaching equilibrium. Furthermore, using a rotating trough, the SH signals of TPPA0 monolayer on the three interfaces under the p-in/pout polarization are nearly unchanged during the measurement. These results indicated that all of the SH signal changes with time are induced by local accumulated heat with repetitive laser excitation at 82 MHz. At last, we propose a molecular mechanism to explain the changes of the SH signal on TPPA0 monolayers. The cooperative action of laser-induced thermal effects and the ionic coordination cause the signal change with time, which means the order of the porphyrin derivatives selfassembled interface is affected by the combination of ions and heat. The finding in this work is important to the bioscience, as well as the functional molecular devices.
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