Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS-CoV-2 Variants.

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.

Estimation of Cooling Rate of High-Strength Thick Plate Steel during Water Quenching Based on a Dilatometric Experiment.

The microstructure and hardness along the thickness direction of a water-quenched, high-strength thick plate with a thickness of 40 mm were investigated with three specimens from the thick plate: surface, 1/4t, and 1/2t (center) thickness, and the phase transformation behavior of the thick plate according to the cooling rate was analyzed through dilatometric experiments. Finally, the cooling rate for each thickness of the thick plate was estimated by comparing the microstructure and hardness of the thick plate along with the thickness with those of the dilatometric specimens. Martensite microstructure was observed on the surface of the water-quenched thick plate due to the fast cooling rate. On the other hand, an inhomogeneous microstructure was transformed inside the thick plate due to the relatively slow cooling rate and central segregation of Mn. A small fraction of bainite was shown at 1/4t thickness. A banded microstructure with martensite and bainite resulting from Mn segregation was developed at 1/2t; that is, the full martensite microstructure was transformed in the Mn-enriched area even at a slow cooling rate due to high hardenability, but a bainite microstructure was formed in the Mn-depleted area owing to relatively low hardenability. A portion of martensite with fine cementite at the surface and 1/4t was identified as auto-tempered martensite with a Bagaryatskii orientation relationship between the ferrite matrix and cementite. The microstructure and hardness as well as dilatation were investigated at various cooling rates through a dilatometric experiment, and a continuous cooling transformation (CCT) diagram was finally presented for the thick plate. Comparing the microstructure and hardness at the surface, 1/4t, and 1/2t of the thick plate with those of dilatometric specimens cooled at various cooling rates, it was estimated that the surface of the thick plate was cooled at more than 20 °C/s, whereas the 1/4t region was cooled at approximately 5~10 °C/s during water quenching. Despite the difficulty in estimation of the cooling rate of 1/2t due to the banded structure, the cooling rate of 1/2t was estimated between 3 and 5 °C/s based on the results of an Mn-depleted zone.

Nanodisc-Mediated Conversion of Virustatic Antiviral Antibody to Disrupt Virus Envelope in Infected Cells.

Many antibody-based antivirals, including broadly neutralizing antibodies (bnAbs) against various influenza virus strains, suffer from limited potency. A booster of the antiviral activity of an antibody is expected to facilitate development of antiviral therapeutics. In this study, a nanodisc (ND), a discoidal lipid bilayer encircled by membrane scaffold proteins, is engineered to provide virucidal properties to antibodies, thereby augmenting their antiviral activity. NDs carrying the Fc-binding peptide sequence form an antibody-ND complex (ANC), which can co-endocytose into cells infected with influenza virus. ANC efficiently inhibits endosome escape of viral RNA by dual complimentary mode of action. While the antibody moiety in an ANC inhibits hemagglutinin-mediated membrane fusion, its ND moiety destroys the viral envelope using free hemagglutinins that are not captured by antibodies. Providing virus-infected host cells with the ability to self-eliminate by the synergistic effect of ANC components dramatically amplifies the antiviral efficacy of a bnAb against influenza virus. When the efficacy of ANC is assessed in mouse models, administration of ANCs dramatically reduces morbidity and mortality compared to bnAb alone. This study is the first to demonstrate the novel nanoparticle ANC and its role in combating viral infections, suggesting that ANC is a versatile platform applicable to various viruses.

A new class of lightweight, stainless steels with ultra-high strength and large ductility.

Steel is the global backbone material of industrialized societies, with more than 1.8 billion tons produced per year. However, steel-containing structures decay due to corrosion, destroying annually 3.4% (2.5 trillion US$) of the global gross domestic product. Besides this huge loss in value, a solution to the corrosion problem at minimum environmental impact would also leverage enhanced product longevity, providing an immense contribution to sustainability. Here, we report a leap forward toward this aim through the development of a new family of low-density stainless steels with ultra-high strength (> 1 GPa) and high ductility (> 35%). The alloys are based on the Fe-(20-30)Mn-(11.5-12.0)Al-1.5C-5Cr (wt%) system and are strengthened by dispersions of nano-sized Fe3AlC-type κ-carbide. The alloying with Cr enhances the ductility without sacrificing strength, by suppressing the precipitation of κ-carbide and thus stabilizing the austenite matrix. The formation of a protective Al-rich oxide film on the surface lends the alloys outstanding resistance to pitting corrosion similar to ferritic stainless steels. The new alloy class has thus the potential to replace commercial stainless steels as it has much higher strength at similar formability, 17% lower mass density and lower environmental impact, qualifying it for demanding lightweight, corrosion resistant, high-strength structural parts.

Measurement of band offsets in Y2O3/InGaZnO4 heterojunctions.

The valence band discontinuity (ΔE(v)) of Y2O3/InGaZnO4 (IGZO) heterojunctions was measured by a core-level photoemission method. The Y2O3 exhibited a band gap of -6.27 eV from absorption measurements. A value of ΔE(v) = 0.44 ± 0.21 eV was obtained by using the Ga 2p3/2, Zn 2p3/2 and in 3d5/2 energy levels as references. Given the experimental bandgap of 3.2 eV for the IGZO, this would indicate a conduction band offset ΔE(c) of - 2.63 eV in the Y2O3/IGZO heterostructures and a nested interface band alignment.

Low temperature growth and optical properties of ZnO nanowires using an aqueous solution method.

ZnO nanowires were grown on indium tin oxide (ITO) coated glass substrates at a low temperature of 90 degrees C using an aqueous solution method. The ZnO seeds were coated on the ITO thin films by using a spin coater. ZnO nanowires were formed in an aqueous solution containing zinc nitrate hexahydrate (Zn(NO3)2 x 6H2O) and hexamethylenetetramine (C6H12N4). The pH value and concentration of the solution play an important role in the growth and morphologies of ZnO nanowires. The size of ZnO naonowires increased as the concentration of the solution increased. It was formed with a top surface of hexagonal and tapered shape at low and high pH values respectively. Additionally, the single crystalline structure and optical property of the ZnO nanowires were investigated using high-resolution transmission electron microscopy and photoluminescence spectroscopy.