The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus ...into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including
, a broad-spectrum antiviral drug that interferes with the viral replication, and
, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.
•It is time to develop next-generation phenotyping techniques for plant phenomics.•LiDAR presents the potential of constituting next-generation phenotyping technology.•The review suggests that ...current LiDAR cannot fully support accomplishing this task.•A preview of the LiDAR forms now in research and development indicates a possibility.•This work shows a novel way of advancing phenotyping and phenomics into a new stage.
Plant phenomics, the link between plant genomics and environment, recently is explosively highlighted. As its basis, a large variety of phenotyping approaches have been developed, but meanwhile, the related technical demands have gone ahead into the levels of high-throughput, field and comprehensive phenotyping. This reality-lagging-behind situation suggests that it is time to envisage the next-generation techniques of plant phenotyping. From the perspective of noninvasive measurement of phenotypic traits, the state-of-the-art remote sensing technology of light detection and ranging (LiDAR) shows the potential. In fact, researchers are calling for more incorporations of LiDAR into phenotyping facilities. At the same time, it has also been realized that the currently-available LiDAR forms cannot effectively support the development of the next-generation techniques of plant phenotyping. In order to bridge this technical gap, the theoretically more-powerful LiDAR variant forms now in research and development, such as high-density, full-waveform and hyperspectral LiDAR, were previewed. Their supposed advanced capacities mean a higher possibility of pushing forward plant phenotyping into a new stage. Overall, with LiDAR determined as a key technical constituent, this study pointed out a novel way for developing the next-generation plant phenotyping techniques, which will be helpful for biologists and agronomists to investigate plant phenomes.
Neoadjuvant immunotherapy and chemotherapy have improved the major pathological response (MPR) in patients with early-stage operable non-small cell lung cancer (NSCLC). This study aimed to assess ...whether the presence of targetable driver mutations affects the efficacy of the combination of immunotherapy and chemotherapy. We enrolled patients with early-stage operable NSCLC who received preoperative neoadjuvant therapy between January 1, 2017, and December 30, 2020. Neoadjuvant therapy was delivered with platinum-doublet chemotherapy; moreover, pembrolizumab was added at the attending physician's discretion based on patient's request. Pathological responses were assessed; moreover, disease-free survival was estimated. Next-generation sequencing was performed in case sufficient preoperative biopsy specimens were obtained. We included 23 patients; among them, 11 received a combination of neoadjuvant immunotherapy and chemotherapy while 12 received neoadjuvant chemotherapy alone. The MPR and pathological complete response rates were 54.5% and 27.3%, respectively, in patients who received a combination of neoadjuvant immunotherapy and chemotherapy. These rates were significantly higher than those in patients who only received neoadjuvant chemotherapy. Three patients in the combination group experienced disease recurrence during the follow-up period even though two of them showed an MPR. These three patients had targetable driver mutations, including an EGFR exon 20 insertion, EGFR exon 21 L858R substitution, and MET exon 14 skipping. Only one patient who remained disease-free had a targetable driver mutation. Among patients with early-stage operable NSCLC requiring neoadjuvant therapy, comprehensive genomic profiling is crucial before the administration of the combination of neoadjuvant immunotherapy and chemotherapy.
Highly responsive organic image sensors are crucial for medical imaging applications. To enhance the pixelwise photoresponse in an organic image sensor, the integration of an organic photodetector ...with amplifiers, or the use of a highly responsive organic photodetector without an additional amplifying component, is required. The use of vertically stacked, two‐terminal organic photodetectors with photomultiplication is a promising approach for highly responsive organic image sensors owing to their simple two‐terminal structure and intrinsically large responsivity. However, there are no demonstrations of an imaging sensor array using organic photomultiplication photodetectors. The main obstacle to a sensor array is the weak‐light sensitivity, which is limited by a relatively large dark current. Herein, a highly responsive organic image sensor based on monolithic, vertically stacked two‐terminal pixels is presented. This is achieved using pixels of a vertically stacked diode‐type organic photodetector with photomultiplication. Furthermore, applying an optimized injection electrode and additionally stacked rectifying layers, this two‐terminal device simultaneously demonstrates a high responsivity (>40 A W−1), low dark current, and high rectification under illumination. An organic image sensor based on this device with an extremely simple architecture exhibits a high pixel photoresponse, demonstrating a weak‐light imaging capability even at 1 µW cm−2.
A highly responsive organic image sensor based on vertically stacked two‐terminal pixels is achieved with pixels of a diode‐type organic photodetector through photomultiplication. With an optimized injection electrode and additionally stacked rectifying layers, the organic image sensor with an extremely simple architecture exhibits a high pixel photoresponse and demonstrates a weak‐light imaging capability at 1 µW cm−2.
The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the ...current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.
•Artificial intelligence (AI) significantly promotes technological innovation.•AI promotes technological innovation by knowledge creation and spillover, learning and absorption, and investment in ...R&D.•This paper empirically tests the promotional effect of AI on technological innovation and its sector heterogeneity.
This paper analyzes the impact of artificial intelligence (AI) on technological innovation through logic reasoning and empirical modeling. Based on the industrial robot data provided by the International Federation of Robotics (IFR) and the panel data of China's 14 manufacturing sectors from 2008 to 2017, this paper empirically analyzes the impact of AI on technological innovation. Our analysis shows that the mechanism of how AI affects technological innovation is that the former promotes technological innovation through accelerating knowledge creation and technology spillover, improving learning and absorptive capacities, while increasing R&D and talent investment. Our empirical results indicate that under the condition of controlling intensity of R&D investment, FDI, ownership structure, technical imitation, AI significantly promotes technological innovation. And the impact of AI on technological innovation experiences sector heterogeneity: AI has more significant impact on the technological innovation of low-tech sectors. The higher the level of AI, the greater its impact on technological innovation. Based on our established conclusions, we provide corresponding suggestions and recommendations for managerial decision-making.
Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and ...genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.
This article presents the 38-GHz phased array 32-element Tx and 16-element Rx with 2-GHz IF and 5-GHz LO for fifth-generation (5G) millimeter-wave (MMW) communications. The Tx and Rx beamformers and ...upconverters/downconverters are fabricated in 65-nm CMOS. The PAs and LNAs near antenna ends are fabricated in 0.15-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> GaAs pHEMT. The eight-element Tx and four-element Rx phased array printed circuit board (PCB) modules integrated with multiple integrated circuits (ICs) and endfire antennas are implemented as unit cells. Four pieces of Tx modules are vertically stacked to construct an <inline-formula> <tex-math notation="LaTeX">8\times {4} </tex-math></inline-formula> brick array (planar array), while four Rx modules are to construct a <inline-formula> <tex-math notation="LaTeX">4\times {4} </tex-math></inline-formula> array. According to 38-GHz over-the-air (OTA) measurements, the 32-element Tx shows 47.5-dBm equivalent isotropic radiated power (EIRP) at OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1 ~dB}} </tex-math></inline-formula> with −35.2-dB image rejection ratio (IMRR) and −37.4-dB <inline-formula> <tex-math notation="LaTeX">\times 8 </tex-math></inline-formula> LORR. The 16-element Rx at 38 GHz shows −4-dBm OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1~dB}} </tex-math></inline-formula> with −28-dB IMRR and −36.6-dB LORR. The Tx and Rx support the beam scanning around ±60° azimuth and ±30° elevation planes. The Tx-to-Rx wireless data link demonstrates 64 quadrature amplitude modulation (QAM)/400 M-BR, 256 QAM/200 M-BR, and 512 QAM/100 M-BR in 20 m. To the best of our knowledge, this work is the first 5G 37-/39-GHz phased array Tx/Rx using the scalable brick array configuration and demonstrating competitive performances compared with previous works.
Although perovskites are extensively investigated in many areas, studies using perovskites as catalysts to activate oxidants for chemical oxidations are still quite limited. While various transition ...metals can be inserted into perovskites to form different perovskites, it is critical to investigate the effects of various transition metallic substituents on the activation of oxidants in chemical oxidation reactions. In this study, we propose to evaluate various metallic substituents in Lanthanum (La)-based perovskites (LaMO3 (M: Co, Cu, Fe and Ni)) for activating a strong oxidant, peroxymonosulfate (POMS), in order to degrade organic contaminants. Rhodamine B (RB) decolorization is used as a model test to evaluate generation of sulfate radicals from activation of POMS by LaMO3. LaCoO3 was found to exhibit the highest catalytic activity, followed by LaNiO3, LaCuO3 and then LaFeO3. LaCoO3 was then selected as a representative LaMO3 to be further investigated for the behavior of POMS activation under various conditions. LaCoO3-activated POMS was favorable under neutral conditions and at high temperatures, but less effective in the presence of NaCl. The mechanism of RB decolorization by LaCoO3-activated POMS was elucidated by examining the effects of radical inhibitors and attributed primarily to sulfate radicals and hydroxyl radicals to a lesser extent. We also found that both La3+ and Co3+/Co2+ ions contribute to catalytic decomposition of POMS for yielding sulfate radicals. LaCoO3 was also shown to activate POMS for RB decolorization over multiple trials without losing efficiency. These results reveal that LaCoO3 is a recyclable and effective La-based perovskite for POMS activation, which can be used for degradation of organic contaminants.
•LaMO3 (M: Co, Cu, Fe, and Ni) are studied for activating peroxymonosulfate (POMS).•RB decolorization is used as a model test to evaluate POMS activation by LaMO3.•Kinetics and activation energies of RB decolorization by LaMO3 are determined.•LaCoO3 is the most effective LaMO3 to activate POMS for degrading RB dye.•Mechanisms of RB decolorization and activation of POMS by LaCoO3 are revealed.
Transplantation of solid organs from donors with active SARS‐CoV‐2 infection has been advised against due to the possibility of disease transmission to the recipient. However, with the exception of ...lungs, conclusive data for productive infection of transplantable organs do not exist. While such data are awaited, the organ shortage continues to claim thousands of lives each year. In this setting, we put forth a strategy to transplant otherwise healthy extrapulmonary organs from SARS‐CoV‐2‐infected donors. We transplanted 10 kidneys from five deceased donors with new detection of SARS‐CoV‐2 RNA during donor evaluation in early 2021. Kidney donor profile index ranged from 3% to 56%. All organs had been turned down by multiple other centers. Without clear signs or symptoms, the veracity of timing of SARS‐CoV‐2 infection could not be confirmed. With 8–16 weeks of follow‐up, outcomes for all 10 patients and allografts have been excellent. All have been free of signs or symptoms of donor‐derived SARS‐CoV‐2 infection. Our findings raise important questions about the nature of SARS‐CoV‐2 RNA detection in potential organ donors and suggest underutilization of exceptionally good extrapulmonary organs with low risk for disease transmission.
The authors present a case series of successful kidney transplantation from donors with newly detected SARS‐CoV‐2, highlighting the potential underutilization of such organs.
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