To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L ...(CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
Nanotechnology has become more and more potentially used in diagnosis or treatment of diseases. Advances in nanotechnology have led to new and improved nanomaterials in biomedical applications. ...Common nanomaterials applicable in biomedical applications include liposomes, polymeric micelles, graphene, carbon nanotubes, quantum dots, ferroferric oxide nanoparticles, gold nanoparticles (Au NPs), and so on. Among them, Au NPs have been considered as the most interesting nanomaterial because of its unique optical, electronic, sensing and biochemical properties. Au NPs have been potentially applied for medical imaging, drug delivery, and tumor therapy in the early detection, diagnosis, and treatment of diseases. This review focuses on some recent advances in the use of Au NPs as drug carriers for the intracellular delivery of therapeutics and as molecular nanoprobes for the detection and monitoring of target molecules.
This paper proposes an accounting framework that breaks up a country's gross exports into various value-added components by source and additional double-counted terms. Our parsimonious framework ...bridges a gap between official trade statistics (in gross value terms) and national accounts (in value-added terms), and integrates all previous measures of vertical specialization and value-added trade in the literature into a unified framework. To illustrate the potential of such a method, we present a number of applications including re-computing revealed comparative advantages and the magnifying impact of multi-stage production on trade costs.
Understanding the evolution mechanism of nuclear power technology development is crucial for predicting its future path and devising a sound strategic plan. While classical economic theory provides ...the relationships between of technological progress and economic growth on specific assumptions, it is necessary to explore the evolutionary mechanism of technology development without prior assumptions. Furthermore, given the various forms of technological development, including basic research, patent technology, and product trade, the intricate relationship between them and economic growth necessitates further elucidation. This study aims to shed light on the evolutionary process of nuclear power technology development by constructing complex systems of “Science-Technology-Product-Economic growth,” applying Bayesian dynamic system modeling methods to establish the evolutionary equation of the complex systems and revealing the historical track and future evolution of nuclear power technology development. This study offers a fresh perspective to unravel the evolution of nuclear power technology development, facilitates a nuanced characterization of energy technology progress, and assists in developing an optimized learning curve for energy technology.
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•Applying Bayesian dynamic system modeling to reveal the historical evolution.•The changes in science and technology are influenced by economic growth.•The changes in the product are mainly influenced by itself.•The changes in economic growth are influenced by both itself and product.
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
Feature selection approaches based on mutual information can be roughly categorized into two groups. The first group minimizes the redundancy of features between each other. The second group ...maximizes the new classification information of features providing for the selected subset. A critical issue is that large new information does not signify little redundancy, and vice versa. Features with large new information but with high redundancy may be selected by the second group, and features with low redundancy but with little relevance with classes may be highly scored by the first group. Existing approaches fail to balance the importance of both terms. As such, a new information term denoted as Independent Classification Information is proposed in this paper. It assembles the newly provided information and the preserved information negatively correlated with the redundant information. Redundancy and new information are properly unified and equally treated in the new term. This strategy helps find the predictive features providing large new information and little redundancy. Moreover, independent classification information is proved as a loose upper bound of the total classification information of feature subset. Its maximization is conducive to achieve a high global discriminative performance. Comprehensive experiments demonstrate the effectiveness of the new approach.
•Public acceptance of autonomous electric vehicles (AEVs) is surveyed online.•This study focuses on the environmental benefits of AEVs.•Environmental concern is an important stimulus to influence the ...adoption of AEVs.•Green perceived usefulness has a powerful effect on using intention of AEVs.
The development of electric vehicles (EVs) and autonomous vehicles (AVs) has made great progress and been expected to play an important role in a future transport system. Some researchers have explored the potential impacts of autonomous electric vehicles (AEVs), while few have focused on the public attitude towards AEVs. This paper aims to understand the public acceptance of AEVs through the application of Technology Acceptance Model. Considering the potential environmental benefits of AEVs, this study concentrates on how environmental concern affects AEVs acceptance. Data is collected from an online survey in China and analyzed by a structural model. The results indicate that green perceived usefulness, perceived ease of use and environmental concern have a positive relationship with people’s intentions to use AEVs. Environmental concern poses a powerful indirect effect on using intention through mediating effects. Implications for improving the public acceptance of AEVs and suggestions for further research are given correspondingly in this study.
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