Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by ...covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses.
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•RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses•Nanoparticle vaccines protect against SARS-CoV-2 infection in mice•HR antigens elicit both humoral and cellular immune responses•HR antigens within nanoparticles contribute to cross-protective immunity
Ma et al. construct two Ferritin-based nanoparticle vaccines that conjugate RBD and HR antigens in SARS-CoV-2 Spike protein utilizing the SpyTag/SpyCatcher system. RBD and RBD-HR nanoparticles vaccines elicit more potent neutralizing antibody responses and stronger T cell immune responses than monomers. HR-containing nanoparticles induce cross-reactive immune responses against other coronaviruses.
This study investigated the surface oxidation process of near equiatomic NiTi at elevated temperatures in air. The surface oxidation is found to involve the formation of several distinctive product ...layers in a particular sequence. The oxidation initiates by selective leaching of Ti from the alloy matrix to form an outer TiO2 layer, resulting in Ti depletion within the matrix and the formation of an inner TiNi3 layer. Further oxidation leads to the formation of a composite layer consisting of TiO2 and Ni(Ti) in between the outer TiO2 and the inner TiNi3 layers when the TiNi3 layer reaches a critical thickness. This marks the onset of a steady state oxidation with the continuous expansion of the composite layer and inward movement of the inner TiNi3 layer. The chemical reactions for the formation of various layers are identified and a diffusion-based physical model is proposed to explain the oxidation process. Surface oxidation resulted in the significant decrease of the latent heat and increase of the critical stress for inducing the martensitic transformation of the oxidised samples, due to the formation of oxidation-related layers and a significant Ti-depleted zone underneath.
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•Clarified the mechanism of the complex process of surface oxidation of NiTi.•Established a diffusion-based theory for the oxidation mechanism of NiTi.•Revealed the formation sequence of multilayer products in oxidation of NiTi.•Characterized effects of surface oxidation on transformation behaviour of NiTi.•Characterized effects of surface oxidation on mechanical properties of NiTi.
COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and ...the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild, and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.
This study explored a novel intermetallic composite design concept based on the principle of lattice strain matching enabled by the collective atomic load transfer. It investigated the hard-soft ...microscopic deformation behavior of a Ti3Sn/TiNi eutectic hard-soft dual phase composite by means of in situ synchrotron high-energy X-ray diffraction (HE-XRD) during compression. The composite provides a unique micromechanical system with distinctive deformation behaviors and mechanisms from the two components, with the soft TiNi matrix deforming in full compliance via martensite variant reorientation and the hard Ti3Sn lamellae deforming predominantly by rigid body rotation, producing a crystallographic texture for the TiNi matrix and a preferred alignment for the Ti3Sn lamellae. HE-XRD reveals continued martensite variant reorientation during plastic deformation well beyond the stress plateau of TiNi. The hard and brittle Ti3Sn is also found to produce an exceptionally large elastic strain of 1.95% in the composite. This is attributed to the effect of lattice strain matching between the transformation lattice distortion of the TiNi matrix and the elastic strain of Ti3Sn lamellae. With such unique micromechanic characteristics, the composite exhibits high strength and large ductility.
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Influenza A virus (IAV) infection is a complicated process. After IAVs spread to the lung, extensive pro-inflammatory cytokines and chemokines are released, which largely determine the outcome of ...infection. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of more than 16,000 immune cells in the pulmonary tissue of infected mice, and demonstrated that two waves of pro-inflammatory factors were released. A group of IAV-infected PD-L1+ neutrophils were the major contributor to the first wave at an earlier stage (day 1-3 post infection). Notably, at a later stage (day 7 post infection) when IAV was hardly detected in the immune cells, a group of platelet factor 4-positive (Pf4+)-macrophages generated another wave of pro-inflammatory factors, which were probably the precursors of alveolar macrophages (AMs). Furthermore, single-cell signaling map identified inter-lineage crosstalk between different clusters and helped better understand the signature of PD-L1+ neutrophils and Pf4+-macrophages. Our data characteristically clarified the infiltrated immune cells and their production of pro-inflammatory factors during the immunopathogenesis development, and deciphered the important mechanisms underlying IAV-driven inflammatory reactions in the lung.
Sustained attention is one of the basic abilities of humans to maintain concentration on relevant information while ignoring irrelevant information over extended periods. The purpose of the review is ...to provide insight into how to integrate neural mechanisms of sustained attention with computational models to facilitate research and application. Although many studies have assessed attention, the evaluation of humans' sustained attention is not sufficiently comprehensive. Hence, this study provides a current review on both neural mechanisms and computational models of visual sustained attention. We first review models, measurements, and neural mechanisms of sustained attention and propose plausible neural pathways for visual sustained attention. Next, we analyze and compare the different computational models of sustained attention that the previous reviews have not systematically summarized. We then provide computational models for automatically detecting vigilance states and evaluation of sustained attention. Finally, we outline possible future trends in the research field of sustained attention.
Functionally graded shape memory alloys have the advantage of combining the functionalities of the shape memory effect and those of functionally graded structures. By proper design, they can exhibit ...new and complex deformation behaviour that is unmatched in uniform shape memory alloys. One obvious advantage of functionally graded shape memory alloys is their widened transformation stress and temperature windows that provide improved controllability in actuating applications. This paper reports on the concept, fabrication, experimentation and thermomechanical behaviour of several designs of functionally graded NiTi alloys, including compositionally graded, microstructurally graded and geometrically graded NiTi alloys, and the various techniques that may be used to create these functionally graded materials. It is found that the property gradients created along the loading direction or perpendicular to the loading direction produce distinct thermomechanical behaviours. The property gradient along the loading direction provides stress gradient over stress-induced transformation, which can be adjusted by the property gradient profile. The property gradient through the thickness direction of plate specimens and perpendicular to the loading direction provides four-way shape memory behaviour during stress-free thermal cycling after tensile deformation.
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•Functionally graded shape memory alloys provide widened transformation stress and temperature windows in actuation application.•The property gradient was achieved in three ways: microstructural gradient, compositional gradient and geometrical gradient.•Property gradients created along the loading direction or perpendicular to that direction produce distinct thermomechanical behaviours.•A variety of techniques has been proposed for fabricating functionally graded shape memory alloy structures.
The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP) and is the functional unit for viral RNA ...transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent of its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex.
The interaction between the influenza virus vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for the influenza virus life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza virus transmission and pathogenicity. Importantly, as an interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.
•Our study utilized stereo-electroencephalogram to investigate the dynamic interaction between attentional control and habituation processes in the prefrontal cortex, providing insights into how ...these fundamental mechanisms synergize during cognitive tasks.•Two distinct neural pathways within the subregions of prefrontal cortex are identified – a bottom-up dominant pathway orchestrated by the IFG, facilitating habitual responses, and a top-down dominant pathway modulated by the OFC, enabling attentional control to override ingrained habits.•Through an information model, we unveil unique patterns of information flow within the subregions of prefrontal cortex, particularly during color-word congruent and incongruent conditions, contributing to a comprehensive understanding of attentional regulation mechanisms.
Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.
Image classification techniques have succeeded greatly on various large-scale visual datasets using deep convolution neural networks. However, previous deep models usually suffer severe performance ...degradation in highly skewed datasets, which restricts their practical application. In this paper, we propose a novel Hierarchical Rebalancing Dual-Classifier model for long-tailed recognition. To better identify the tail samples and maintain the performance of head classes, we propose a dual-classifier framework with a uniform sampler for performing their duties. For balancing the learning of feature representation and classifiers, a dynamic weight is introduced to adjust the model's attention. To alleviate the feature deviation between training data and testing data, a hierarchical rebalancing loss is designed for the re-weighting branch, which adjusts the decision values in predicted logits to facilitate the model actively compensating for tail categories. Finally, we conduct extensive experiments on standard long-tailed benchmarks Cifar10-LT, Cifar100-LT, ImageNet-LT, and iNaturalist2018, demonstrating the effectiveness and superiority of our HRDC.
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