ABSTRACT
Elastic stability is the basis for understanding structural responses to external stimuli in crystalline solids, including melting, incipient plasticity and fracture. In this work, elastic stability is investigated in a series of high-entropy alloys (HEAs) using in situ mechanical tests and atomic-resolution characterization in transmission electron microscopy. Under tensile loading, the HEA lattices are observed to undergo a sudden loss of ordering as the elastic strain reached â½ 10%. Such elastic strain-induced amorphization stands in intrinsic contrast to previously reported dislocation-mediated elastic instability and defect accumulation-mediated amorphization, introducing a form of elastic instability. Together with the first principle calculations and atomic-resolution chemical mapping, we identify that the elastic strain-induced amorphization is closely related to the depressed dislocation nucleation due to the local atomic environment inhomogeneity of HEAs. Our findings provide insights for the understanding of the fundamental nature of physical mechanical phenomena like elastic instability and incipient plasticity.
ABSTRACT
Although there are indications of a trend towards less severe acute respiratory symptoms and a decline in overall lethality from the novel Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), more and more attention has been paid to the long COVID, including the increased risk of Alzheimer's disease (AD) in COVID-19 patients. In this study, we aim to investigate the involvement of N-terminal amyloid precursor protein (APP) in SARS-CoV-2-induced amyloid-ß (Aß) pathology. Utilizing both in vitro and in vivo methodologies, we first investigated the interaction between the spike protein of SARS-CoV-2 and N-terminal APP via LSPR and CoIP assays. The in vitro impacts of APP overexpression on virus infection were further evaluated in HEK293T/ACE2 cells, SH-SY5Y cells, and Vero cells. We also analyzed the pseudovirus infection in vivo in a mouse model overexpressing human wild-type APP. Finally, we evaluated the impact of APP on pseudovirus infection within human brain organoids and assessed the chronic effects of pseudovirus infection on Aß levels. We reported here for the first time that APP, the precursor of the Aß of AD, interacts with the Spike protein of SARS-CoV-2. Moreover, both in vivo and in vitro data further indicated that APP promotes the cellular entry of the virus, and exacerbates Aß-associated pathology in the APP/PS1 mouse model of AD, which can be ameliorated by N-terminal APP blockage. Our findings provide experimental evidence to interpret APP-related mechanisms underlying AD-like neuropathology in COVID-19 patients and may pave the way to help inform risk management and therapeutic strategies against diseases accordingly.
Subject(s)
Alzheimer Disease , COVID-19 , Virus Internalization , Animals , Humans , Mice , Alzheimer Disease/complications , Alzheimer Disease/virology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Chlorocebus aethiops , COVID-19/complications , Disease Models, Animal , HEK293 Cells , Mice, Transgenic , Post-Acute COVID-19 Syndrome , Presenilin-1 , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus , Vero CellsABSTRACT
Oxygen solute strengthening is an effective strategy to harden alloys, yet, it often deteriorates the ductility. Ordered oxygen complexes (OOCs), a state between random interstitials and oxides, can simultaneously enhance strength and ductility in high-entropy alloys. However, whether this particular strengthening mechanism holds in other alloys and how these OOCs are tailored remain unclear. Herein, we demonstrate that OOCs can be obtained in bcc (body-centered-cubic) Ti-Zr-Nb medium-entropy alloys via adjusting the content of Nb and oxygen. Decreasing the phase stability enhances the degree of (Ti, Zr)-rich chemical short-range orderings, and then favors formation of OOCs after doping oxygen. Moreover, the number density of OOCs increases with oxygen contents in a given alloy, but adding excessive oxygen (>3.0 at.%) causes grain boundary segregation. Consequently, the tensile yield strength is enhanced by ~75% and ductility is substantially improved by ~164% with addition of 3.0 at.% O in the Ti-30Zr-14Nb MEA.
ABSTRACT
SARS-CoV-2 invades host cells mainly through the interaction of its spike-protein with host cell membrane ACE2. Various antibodies targeting S-protein have been developed to combat COVID-19 pandemic; however, the potential risk of antibody-dependent enhancement and novel spike mutants-induced neutralization loss or antibody resistance still remain. Alternative preventative agents or therapeutics are still urgently needed. In this study, we designed series of peptides with either ACE2 protecting or Spike-protein neutralizing activities. Molecular docking predicted that, among these peptides, ACE2 protecting peptide AYp28 and Spike-protein neutralizing peptide AYn1 showed strongest intermolecular interaction to ACE2 and Spike-protein, respectively, which were further confirmed by both cell- and non-cell-based in vitro assays. In addition, both peptides inhibited the invasion of pseudotype SARS-CoV-2 into HEK293T/hACE2 cells, either alone or in combination. Moreover, the intranasal administration of AYp28 could partially block pseudovirus invasion in hACE2 transgenic mice. Much more importantly, no significant toxicity was observed in peptides-treated cells. AYp28 showed no impacts on ACE2 function. Taken together, the data from our present study predicted promising preventative and therapeutic values of peptides against COVID-19, and may prove the concept that cocktail containing ACE2 protecting peptides and spike neutralizing peptides could serve as a safe and effective approach for SARS-CoV-2 prevention and therapy.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Animals , COVID-19/virology , Female , HEK293 Cells , Humans , Immunohistochemistry , Mice , Mice, TransgenicABSTRACT
Noise and mechanical vibrations not only cause damage to devices, but also present major public health hazards. High-damping alloys that eliminate noise and mechanical vibrations are therefore required. Yet, low operating temperatures and insufficient strength/ductility ratios in currently available high-damping alloys limit their applicability. Using the concept of high-entropy alloy (HEA), we present a class of high-damping materials. The design is based on refractory HEAs, solid-solutions doped with either 2.0 atomic % oxygen or nitrogen, (Ta0.5Nb0.5HfZrTi)98O2 and (Ta0.5Nb0.5HfZrTi)98N2. Via Snoek relaxation and ordered interstitial complexes mediated strain hardening, the damping capacity of these HEAs is as high as 0.030, and the damping peak reaches up to 800 K. The model HEAs also exhibit a high tensile yield strength of ~1400 MPa combined with a large ductility of ~20%. The high-temperature damping properties, together with superb mechanical properties make these HEAs attractive for applications where noise and vibrations must be reduced.
ABSTRACT
Change history: In this Letter, owing to a production error, all the data points (except the two points for O-2 and N-2, respectively) were missing in Fig. 1b. The figure has been corrected online.
ABSTRACT
Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle1-3. Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening4,5, such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs)6-10. The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength-ductility trade-off11. The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs12, by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank-Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations13 do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials.