UM15 reinforces a lymphocyte-mimicking nanotrap for precise HIV-1 inhibition

Even the potential of T cell-mimicking nanotrap for long term viral control due to its overcoming of human immunodeficiency virus(HIV)genetic diversity and viral resistance,the robust HIV inhibition was not expected because these nanotraps displayed no obvious advantages compared with the infinite host cells.Herein,a glycoprotein 120(gp120)-targeting polypeptide UM15 reinforced lymphocyte-mimicking nanotrap was constructed,and its improved HIV-1 inhibiting efficacy was validated.According to the results,the constructed nanotraps exhibited evident escaping ability from uptake of the mononuclear phagocyte system and highly improved binding ability with gp120 proteins.The constructed nanotraps neutralized all tested HIV-1 pseudo typed viruses with IC80 of 21.0μg/mL,and inhibited both X4-tropic and R5-tropic HIV-1 with IC80 of 34.4 and 20.6μg/mL,respectively.Approximately 40%of gp120 was observed to be shed from pseudo virus,and above 40%bystander T cells were prevented from gp120-induced death by the constructed nanotraps.The safety of the constructed nanotraps was confirmed both in vitro and in mice.Therefore,the constructed nanotraps could specifically neutralize free HIV-1,selectively bind with gp120 expressing HIV-1 infected cells,cause gp120 shedding,inhibit gp120-induced bystander T cell killing on the premise of safety,and were considered as promising therapeutic agents for precise inhibition of HIV.

Ultralow oxygen ion diffusivity in pyrochlore-type La_(2)(Zr_(0.7)Ce_(0.3))_(2)O_(7)

Thermally grown oxides(TGOs)at the ceramic top-coat/metallic bond-coat interface are a pressing chal-lenge in advanced thermal barrier coating(TBC)systems as they can affect the performance and ser-vice lifetime of TBCs.Thus,developing novel TBC materials with ultralow oxygen ion diffusivity is very urgent.In this study,we reported the diffusive properties of oxygen ions in a novel pyrochlore-type La_(2)(Zr_(0.7)Ce_(0.3))_(2)O_(7)(LZ7C3)material.The measured ionic conductivity and atomistic simulation revealed that the oxygen ion diffusivity in LZ7C3 grains is two orders of magnitude lower than that in conventional 8 wt.%yttria-stabilized zirconia(8YSZ)grains.This is due to the relatively high energy barrier for oxygen hopping in LZ7C3.In addition,it was found that enhancing the order distribution of cations is a strategy to reduce the intrinsic oxygen diffusion of pyrochlore-type oxides.On the other hand,we observed that La^(3+) cations segregate at the grain boundaries(GBs)of LZ7C3,which results in the electrostatic poten-tial at GBs being comparable to that in the bulk.Furthermore,we found that the oxygen ion diffusion is facilitated at the GBs of LZ7C3 due to the stretched O-Zr/Ce bond and the low coordination at GBs.How-ever,the segregations of Y^(3+)cations and the increase in the number of oxygen vacancies resulted in the formation of an electrostatic layer at the GBs of 8YSZ,which shielded the oxygen ion diffusion.Despite this,the oxygen ion diffusivity in LZ7C3 was still considerably less than that in conventional 8YSZ.This study offers a stepping stone toward utilizing pyrochlore-type LZ7C3 materials as advanced TBCs at high temperatures.