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This system utilizes image recognition technology to study the problems of other people's check-in in the current check-in mode, poor data feedback, and low efficiency of manual management. A complete set of mobile conference sign-based based on image recognition technology is designed and implemented. The management system can greatly improve the efficiency of the conference check-in, save the time of the conference check-in, has strong usability and operability, and greatly saves the conference time occupied by the conference sign-on, and has high efficiency and practicability.

With the increasing demand for mineral resources in China, how to manage mineral resources scientifically, efficiently and intelligently has become a practical problem faced by relevant governments, enterprises and academia. As the most advanced technology of GIS in recent years, Web GIS can collect, store, process, analyze and visualize heterogeneous, multi-source and massive spatial geographic data. Therefore, introducing Web GIS technology into mine information management and building an information system for massive, multi-source and heterogeneous mine information management is of great significance for the government and enterprises to improve the management efficiency of mineral resources and realize the accurate and scientific planning and management of mineral resources.

This brief focuses on reachable set estimation for memristive complex-valued neural networks (MCVNNs) with disturbances. Based on algebraic calculation and Gronwall-Bellman inequality, the states of MCVNNs with bounded input disturbances converge within a sphere. From this, the convergence speed is also obtained. In addition, an observer for MCVNNs is designed. Two illustrative simulations are also given to show the effectiveness of the obtained conclusions.

The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses

Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.

The thermo-optic coupling model was established and used to simulate the thermal anisotropic property of AgGaS2 crystal pumped by carbon dioxide laser at the wavelength of 9.6 um. To acquire the ac...

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that poses significant threats to global public health. Macrophages and dendritic cells are both key sentinel cells in the host immune response and play critical roles in the pathogenesis of flavivirus infections. Recent studies showed that ZIKV could productively infect monocyte-derived dendritic cells (moDCs), but the role of macrophages in ZIKV infection remains incompletely understood. In this study, we first compared ZIKV infection in monocyte-derived macrophages (MDMs) and moDCs derived from the same donors. We demonstrated that while both MDMs and moDCs were susceptible to epidemic (Puerto Rico) and pre-epidemic (Uganda) strains of ZIKV, virus replication was largely restricted in MDMs but not in moDCs. ZIKV induced significant apoptosis in moDCs but not MDMs. The restricted virus replication in MDMs was not due to inefficient virus entry but was related to post-entry events in the viral replication cycle. In stark contrast with moDCs, ZIKV failed to inhibit STAT1 and STAT2 phosphorylation in MDMs. This resulted in the lack of efficient antagonism of the host type I interferon-mediated antiviral responses. Importantly, depletion of STAT2 but not STAT1 in MDMs significantly rescued the replication of ZIKV and the prototype flavivirus yellow fever virus. Overall, our findings revealed a differential interplay between macrophages and dendritic cells with ZIKV. While dendritic cells may be exploited by ZIKV to facilitate virus replication, macrophages restricted ZIKV infection.

Spinal cord injury (SCI) without radiographic abnormality (SCIWORA) is a syndrome that usually occurs in children primarily because of the unique biomechanics of the pediatric spine. We recently found that the histopathological and behavioral effects of SCI with radiographic abnormality (SCIWRA) and SCIWORA are very different from each other in animal models. Although numerous studies were conducted to understand the epidemiological and clinical characteristics of the overall pediatric SCI population and the pediatric SCIWORA population, the characteristics of the pediatric SCIWRA population and their differences from those of the SCIWORA population are poorly understood.To describe the epidemiology and clinical outcomes of pediatric patients with SCIWRA and their differences from those with SCIWORA.Retrospective study.47 pediatric SCIWRA patients.Epidemiological characteristics, Injury severities, functional deficits, and management and recovery outcomes.Review of all cases with SCIWRA at Beijing Children's Hospital between July 2007 and December 2019 and comparison between the present data and our previous SCIWORA data.47 of the 187 pediatric SCI patients had SCIWRA (age: 7.06 ± 3.75 years, male-to-female ratio: 3:2). Main causes of SCIWRA were fall (38%) and traffic accidents (38%). Lesions were often located at multiple levels (62%). Incubation period was 3 ± 18 hours. According to the American Spinal Injury Association impairment scale (AIS), many SCIWRA patients had incomplete impairment (AIS B, 9%; AIS C, 9%; AIS D, 32%). Specifically, many of them had abnormal upper and lower limb muscle powers (55% and 60%), upper and lower limb muscle tones (34% and 49%), sensation (38%), and knee, ankle, and abdominal reflexes (47%, 34%, and 36%). 72% of SCIWRA patients were treated with methylprednisolone, dexamethasone, or both. 81% of them showed neurological improvement before discharge. There was no association between corticosteroid therapy and neurological improvement. Moreover, functional outcomes of their upper and lower limb muscle powers were significantly associated with functional outcomes of their upper and lower limb muscle tones (p0.01), respectively. In comparison to the SCIWRA population, the SCIWORA population had a higher ratio of younger and female patients of sports-related thoracic injuries with long incubation period leading to lower-body deficits and complete impairment (p0.05 or p0.01). Despite all the differences, their neurological improvement was similar (p0.05).Demographic differences exist in the SCIWRA population. Corticosteroids do not appear to be effective in the different types of pediatric SCI. Limb muscle tone may be used to evaluate the functional status of limb muscle power. The epidemiological and clinical characteristics of SCIWRA and SCIWORA are very different from each other. It is important to formulate tailor-made prevention, evaluation, and management strategies for the pediatric population to optimize the SCI outcomes.

Epsilon-poly-L-lysine (ε-PL) is an unusual biopolymer composed of L-lysine produced by several microorganisms, especially by the genus Streptomyces. Due to its excellent antimicrobial activity, good water solubility, high safety, and biodegradable nature, ε-PL with a GRAS status has been widely used in food and pharmaceutical industries. In the past years, studies have focused on the biotechnological production of ɛ-PL, the biosynthetic mechanism of microbial ɛ-PL, and its application. To provide new perspectives from recent advances, the review introduced the methods for the isolation of ɛ-PL producing strains and the biosynthetic mechanism of microbial ɛ-PL. We summarized the strategies for the improvement of ɛ-PL producing strains, including physical and chemical mutagenesis, ribosome engineering and gene engineering, and compared the different metabolic regulation strategies for improving ɛ-PL production, including medium optimization, nutrient supply, pH control, and dissolved oxygen control. Then, the downstream purification methods of ɛ-PL and its recent applications in food and medicine industries were introduced. Finally, we also proposed the potential challenges and the perspectives for the production of ε-PL.

Flexible pressure sensors with high sensitivity over a broad pressure range are highly desired, yet challenging to build to meet the requirements of practical applications in daily activities and more significant in some extreme environments. This work demonstrates a thin, lightweight, and high-performance pressure sensor based on flexible porous phenyl-silicone/functionalized carbon nanotube (PS/FCNT) film. The formed crack-across-pore endows the pressure sensor with high sensitivity of 19.77 kPa

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that BA.2 is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of BA.2 remains unclear and is of critical public health significance. Here we investigated the virological features and pathogenicity of BA.2 with in vitro and in vivo models. We show that BA.2 is less dependent on transmembrane protease serine 2 (TMPRSS2) for virus entry in comparison with BA.1 in vitro. In K18-hACE2 mice, BA.2 replicates more efficiently than BA.1 in the nasal turbinates and replicates marginally less efficiently in the lungs, leading to decreased body weight loss and improved survival. Our study indicates that BA.2 is similarly attenuated in lungs compared with BA.1 but is potentially more transmissible because of its better replication at the nasal turbinates.

"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Mechanistic assays show that H84T-BanLec targets virus entry. High-speed atomic force microscopy depicts real-time multimolecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modeling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the drug compound's broad-spectrum antiviral activity and the lack of resistant mutants.

Brain source mechanisms of the cortical EEG brainwave at the resting state in the elderly during normal aging are rarely known. To solve the problem, we use a standard low-resolution electromagnetic tomography to explore the brain source mechanisms on the effects of healthy aging on brain function at the resting state.Eye-closed EEG signals at resting state were sampled in 13 normal elderly adults and 17 normal young adults. The EEG rhythms by frequency band, delta, theta, alpha 1, alpha 2, beta 1, and beta 2 were of interest for this analysis. Brain sources of these rhythms were estimated by standard low-resolution electromagnetic tomography.Statistical results demonstrated that central, parietal, occipital, and temporal alpha 1 and theta brain sources presented the pattern normal young adultsnormal elderly adults (P0.05), whereas the global beta 1 and beta 2 brain sources presented the pattern normal elderly adultsnormal young adults (P0.05). Moreover, the same is true that amplitude of central, parietal, occipital, and temporal alpha 2 brain sources were lower in normal elderly adults compared with those in normal young adults (P0.05).These results imply that normal aging is linked to cortical neural desynchronization of alpha and delta rhythms and synchronization of beta rhythm in central, parietal, and frontal cortices at resting state.

This paper discusses the reachable set estimation problem of neural networks with mixed delays. Firstly, by means of the maximal Lyapunov–Krasovskii functional, we obtain a non-ellipsoid form of the reachable set. Further more, when calculating the derivative of the maximum Lyapunov functional, the lower bound lemma and reciprocally convex approach method are used to solve the reciprocally convex combination term, which reduce the related decision variables. Secondly, we extend the results to polytopic uncertainties neural networks and consider the case of uncertain differentiable parameters. Finally, two numerical examples and one application example are listed to show the validity of our methods.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in more than 2 000 000 laboratory-confirmed cases including over 145 000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently causes asymptomatic or presymptomatic infections. However, the underlying mechanisms that confer these viral characteristics of high transmissibility and asymptomatic infection remain incompletely understood.MethodsWe comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison.ResultsSARS-CoV-2 infected and replicated in human lung tissues more efficiently than SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20-fold more infectious virus particles than did SARS-CoV from the infected lung tissues (P < .024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative proinflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently.ConclusionsOur study provides the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provide important insights into the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.

Body language is one of the most common ways of expressing human emotion. In this article, we make the first attempt to generate an action video with a specific emotion from a single person image. The goal of the emotion-based action generation task (EBAG) is to generate action videos expressing a specific type of emotion given a single reference image with a full human body. We divide the task into two parts and propose a two-stage framework to generate action videos with specified emotions. At the first stage, we propose an emotion-based pose sequence generation approach (EPOSE-GAN) for translating the emotion to a pose sequence. At the second stage, we generate the target video frames according to the three inputs including the source pose and the target pose as the motion information and the source image as the appearance reference by using conditional GAN model with an online training strategy. Our framework produces the pose sequence and transforms the action independently, which highlights the fundamental role that the high-level pose feature plays in generating action video with a specific emotion. The proposed method has been evaluated on the “Soul Dancer” dataset which is built for action emotion analysis and generation. The experimental results demonstrate that our framework can effectively solve the emotion-based action generation task. However, the gap in the details of the appearance between the generated action video and the real-world video still exists, which indicates that the emotion-based action generation task has great research potential.

SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human populations. The variant contains 34 changes in its spike protein including 15 substitutions at the receptor-binding domain (RBD). While recent reports reveal that the Omicron variant can robustly escape from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown. Here, we investigate the virological features and pathogenesis of the Omicron variant using in vitro and in vivo models. Our results demonstrate that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 but not in VeroE6 cells. Further mechanistic investigations reveal that the Omicron variant is deficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT, Alpha, Beta, and Delta variant, which explained its inefficient replication in Calu3 and Caco2 cells. Importantly, the replication of the Omicron variant is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. Overall, our study demonstrates that the Omicron variant is significantly attenuated in virus replication and pathogenicity in comparison with WT and previous variants. Our data suggest the current global vaccination strategy has forced SARS-CoV-2 into a new evolutionary trajectory towards reduced replication fitness in exchange of better immune escape. These findings are critical for setting policy in the pandemic control and disease management of COVID-19.

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population

Thin, lightweight, and flexible textile pressure sensors with the ability to detect the full range of faint pressure (via a facile electrophoretic deposition (EPD) approach. High-density FCNT is evenly wrapped and chemically bonded to the fiber surface during the EPD process, forming a conductive hierarchical fiber/FCNT matrix. Benefiting from the large compressible region of PI fiber fabric, abundant yet firm contacting points, point-to-point contacting mode, and high elastic modulus of both PI and CNT, the proposed PI/FCNT pressure sensor can be customized and modulated to achieve both a wide linear ranges, ultra-broad sensing range, long-term stability and high-temperature resistance. Thanks to these merits, the proposed PI/FCNT(EPD) pressure sensor could monitor the human physiological information, detect tiny and extremely high pressure, can be integrated into an intelligent mechanical hand to detect the contact force under high-temperature (>300 ºC), endowing it with high applicability in the fields of real-time health monitoring, intelligent robots, and harsh environments.

Background Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance. Methods We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays. Findings Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles. Interpretation Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic. Funding A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Influenza A virus is the main cause of worldwide epidemics and annual influenza outbreaks in humans. In this study, a virtual screen was performed to identify compounds that interact with the PB2 cap-binding domain (CBD) of influenza A polymerase. A virtual screening workflow based on Glide docking was used to screen an internal database containing 8417 molecules, and then the output compounds were selected based on solubility, absorbance, and structural fingerprints. Of the 16 compounds selected for biological evaluation, six compounds were identified that rescued cells from H1N1 virus-mediated death at non-cytotoxic concentrations, with EC50 values ranging from 2.5–55.43 μM, and that could bind to the PB2 CBD of H1N1, with Kd values ranging from 0.081–1.53 μM. Molecular dynamics (MD) simulations of the docking complexes of our active compounds revealed that each compound had its own binding characteristics that differed from those of VX-787. Our active compounds have novel structures and unique binding modes with PB2 proteins, and are suitable to serve as lead compounds for the development of PB2 inhibitors. An analysis of the MD simulation also helped us to identify the dominant amino acid residues that play a key role in binding the ligand to PB2, suggesting that we should focus on increasing and enhancing the interaction between inhibitors and these major amino acids during lead compound optimization to obtain more active PB2 inhibitors.

Mice are not susceptible to wildtype SARS-CoV-2 infection. Emerging SARS-CoV-2 variants including B.1.1.7, B.1.351, P.1, and P.3 contain mutations in spike, which have been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that they may have evolved to expand species tropism to rodents. Here, we investigated the capacity of B.1.1.7 and other emerging SARS-CoV-2 variants in infecting mouse (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Our results show that B.1.1.7 and P.3, but not B.1 or wildtype SARS-CoV-2, can utilize mouse and rat ACE2 for virus entry in vitro. High infectious virus titers, abundant viral antigen expression, and pathological changes are detected in the nasal turbinate and lung of B.1.1.7-inocluated mice and rats. Together, these results reveal that the current predominant circulating SARS-CoV-2 variant, B.1.1.7, has gained the capability to expand species tropism to rodents.

Thin, lightweight, and flexible textile pressure sensors with the ability to precisely detect the full range of faint pressure (via a facile electrophoretic deposition (EPD) approach. High-density FCNT is evenly wrapped and chemically bonded to the fiber surface during the EPD process, forming a conductive hierarchical fiber/FCNT matrix. Benefiting from the abundant yet firm contacting points, point-to-point contacting mode, and high elastic modulus of both PI and CNT, the proposed PI/FCNT pressure sensor exhibits ultra-high sensitivity (3.57 MPa− 1), ultra-wide linearity (3.24 MPa), exceptionally broad sensing range (~ 45 MPa), and long-term stability (> 4000 cycles). Furthermore, under a high working temperature of 200 ºC, the proposed sensor device still shows an ultra-high sensitivity of 2.64 MPa− 1 within a wide linear range of 7.2 MPa, attributing to its intrinsic high-temperature-resistant properties of PI and CNT. Thanks to these merits, the proposed PI/FCNT(EPD) pressure sensor could serve as an E-skin device to monitor the human physiological information, precisely detect tiny and extremely high pressure, and can be integrated into an intelligent mechanical hand to detect the contact force under high-temperature (> 300 ºC), endowing it with high applicability in the fields of real-time health monitoring, intelligent robots, and harsh environments.

Coronaviruses have repeatedly crossed species barriers to cause epidemics1. “Pan-coronavirus” antivirals targeting conserved viral components involved in coronavirus replication, such as the extensively glycosylated spike protein, can be designed. Here we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high-mannose found on viral proteins but seldom on healthy human cells2, potently inhibits the highly virulent MERS-CoV, pandemic SARS-CoV-2 and its variants, and other human-pathogenic coronaviruses at nanomolar concentrations. MERS-CoV-infected human DPP4-transgenic mice treated by H84T-BanLec have significantly higher survival, lower viral burden, and reduced pulmonary damage. Similarly, prophylactic or therapeutic H84T-BanLec is effective against SARS-CoV-2 in hamsters. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Time-of-drug-addition assay shows that H84T-BanLec targets virus entry. Real-time structural analysis with high-speed atomic force microscopy depicts multi-molecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity, and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modelling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the activity against SARS-CoV-2 variants and the lack of resistant mutants. The broad-spectrum H84T-BanLec should be clinically evaluated in respiratory viral infections including COVID-19.

Flexible piezoresistive pressure sensors featuring high sensitivity, wide operating pressure range, and short response time are required urgently due to the rapid development of smart devices and artificial intelligence. Herein, a high-performance flexible piezoresistive pressure sensor based on naturally formed hierarchical flower-shaped SnSe2 nanoplates and conical frustum-like structured polydimethylsiloxane (PDMS) is demonstrated. The micropatterned PDMS/Au and SnSe2 nanoplates/Au interdigital electrodes are exploited as the top and down part of the sensor, respectively. Benefiting from abundant contact sites and sufficient roughness provided by the SnSe2 nanoplates, the proposed sensing devices exhibit significantly enhanced sensitivity as high as 433.22 kPa–1 when compared with conventional configuration (planar Au film as the bottom interdigital electrodes). The resulting pressure sensor (PDMS/Au/Au/SnSe2) also presents wide operating pressure range (0–38.4 kPa), lower limit of detection (∼0.82 Pa), fast response time (∼90 μs), and long-term cycle stability (>4000 cycles). Therefore, it shows a great potential in various applications, such as the detection of the magnitude and distribution of the loaded pressure, as well as the monitoring of the human physiological signals. Ministry of Education (MOE) Nanyang Technological University Accepted version This work was partially supported by the Shenzhen Basic Research Grant (JCYJ20150925163313898, JCYJ20170413153246713, and JCYJ20180507182431967) and the National Nature Science Foundation of China (11804354, 61574157, and 61774164). The authors are also grateful for the support of the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2015-T2-1-066 and MOE2015-T2-2-010), Singapore Ministry of Education Academic Research Fund Tier 1 (RG85/16), and Nanyang Technological University (Start-up grant M4081515 to L.W.).

The interaction between pyridoxal hydrochloride (HQ) and apoCopC was investigated using Fourier transform infrared spectroscopy (FTIR), isothermal titration calorimetry (ITC), circular dichroism (CD), fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, fluorescence lifetime, TNS fluorescence and docking methods. FTIR, CD, TNS fluorescence and fluorescence lifetime experiments suggested that the apoCopC conformation was altered by HQ with an increase in the random coil content and a reduction in the β-sheet content. In addition, the data from fluorescence spectroscopy, 3D fluorescence spectroscopy and molecular docking revealed that the binding site of HQ was located in the hydrophobic area of apoCopC, and a redshift of the HQ fluorescence spectra was observed. Furthermore, ITC and fluorescence quenching data manifested that the binding ratio of HQ and apoCopC was 1:1, and the forming constant was calculated to be (7.06 ± 0.21) × 105 M−1. The thermodynamic parameters ΔH and ΔS suggested that the formation of a CopC-HQ complex depended on the hydrophobic force. Furthermore, the average binding distance between tryptophan in apoCopC and HQ was determined by means of Forster non-radioactive resonance energy transfer and molecular docking. The results agreed well with each other. As a redox switch in the modulation of copper, the interaction of apoCopC with small molecules will affect the action of the redox switch. These findings could provide useful information to illustrate the copper regulation mechanism.

Highly pathogenic coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2, Middle East respiratory syndrome coronavirus (MERS-CoV)3,4, and SARS-CoV-15 vary in their transmissibility and pathogenicity. However, infection by all three viruses result in substantial apoptosis in cell culture6-8 and in patient samples9-11, suggesting a potential link between apoptosis and the pathogenesis of coronaviruses. To date, the underlying mechanism of how apoptosis modulates coronavirus pathogenesis is unknown. Here we show that a cysteine-aspartic protease of the apoptosis cascade, caspase-6, serves as an essential host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid (N) proteins, generating N fragments that serve as interferon (IFN) antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates the lung pathology and body weight loss of SARS-CoV-2-infected golden Syrian hamsters and improves the survival of mouse-adapted MERS-CoV (MERS-CoVMA)-infected human DPP4 knock-in (hDPP4 KI) mice. Overall, our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate their replication. These results further suggest caspase-6 as a potential target of intervention for the treatment of highly pathogenic coronavirus infections including COVID-19 and MERS.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs.

We introduce a principled approach for synthesizing new views of a scene given a single source image. Previous methods for novel view synthesis can be divided into image-based rendering methods (e.g., flow prediction) or pixel generation methods. Flow predictions enable the target view to re-use pixels directly, but can easily lead to distorted results. Directly regressing pixels can produce structurally consistent results but generally suffer from the lack of low-level details. In this paper, we utilize an encoder–decoder architecture to regress pixels of a target view. In order to maintain details, we couple the decoder aligned feature maps with skip connections, where the alignment is guided by predicted depth map of the target view. Our experimental results show that our method does not suffer from distortions and successfully preserves texture details with aligned skip connections.

Infection of highly pathogenic coronaviruses triggers apoptosis that can be targeted to reduce disease severity., Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R–like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2– and SARS-CoV–induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2–inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.

We propose a method for fusing stereo disparity estimation with movement-induced prior information. Instead of independent inference frame-by-frame, we formulate the problem as a non-parametric learning task in terms of a temporal Gaussian process prior with a movement-driven kernel for inter-frame reasoning. We present a hierarchy of three Gaussian process kernels depending on the availability of motion information, where our main focus is on a new gyroscope-driven kernel for handheld devices with low-quality MEMS sensors, thus also relaxing the requirement of having full 6D camera poses available. We show how our method can be combined with two state-of-the-art deep stereo methods. The method either work in a plug-and-play fashion with pre-trained deep stereo networks, or further improved by jointly training the kernels together with encoder-decoder architectures, leading to consistent improvement.

Background And Aims Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. Methods Human intestinal tissues were obtained from patients while undergoing surgical operations at the Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. Results SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with the release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. Conclusion Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human guts, suggesting the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for SARS-2003 and COVID-19, which might be a result of the more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine., SARS-CoV-2 induces a higher innate immune response while replicates less efficiently and induces less cytopathology than SARS-CoV in the human intestinal tissues. These findings potentially explained the differential gastrointestinal manifestations observed in COVID-19 and SARS-2003.

SARS-CoV-2 has affected over 9 million patients with more than 460,000 deaths in about 6 months. Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells, which are not previously reported, may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we reported key host and viral determinants that were essential for efficient SARS-CoV-2 infection in the human lung. First, we identified heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Second, we demonstrated that while cell surface sialic acids significantly restricted SARS-CoV infection, SARS-CoV-2 could largely overcome sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissue explants. Third, we demonstrated that the inserted furin-like cleavage site in SARS-CoV-2 spike was required for efficient virus replication in human lung but not intestine tissues. Overall, these findings contributed to our understanding on efficient SARS-CoV-2 infection of human lungs.

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs., Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

Clinical manifestations of coronavirus disease 2019 (COVID-19) vary from asymptomatic virus shedding, nonspecific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The interplay between SARS-CoV-2 and these cell types remains unknown. We investigated infection and host responses of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. MoDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types and triggered significant proinflammatory cytokine/chemokine expression in MDMs but not moDCs. Investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings may explain the mild and insidious course of COVID-19 until late deterioration.

Highlights • SARS-CoV-2 infection was more robust than SARS-CoV in Calu3. In contrast, SARS-CoV infected intestinal epithelial cells more efficiently. • SARS-CoV-2 infection launched an attenuated interferon and pro-inflammatory cytokines/chemokines response in both Calu3 and Caco2 cells, despite robust virus infection and propagation. • SARS-CoV-2 was more sensitive to IFNβ and poly(I:C) pretreatment than that of SARS-CoV., Objectives Respiratory and intestinal tract were two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking. Methods We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human pulmonary (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV. Results Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL IFN-β (IFNβ) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFNβ and IFN inducer than SARS-CoV in Calu3. Conclusions Despite robust infection efficiency in both the human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.

Summary: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus–host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown. Methods: We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's t test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA. Findings: SARS-CoV-2 infected and replicated to comparable levels in human Caco2 cells and Calu3 cells over a period of 120 h (p=0·52). By contrast, SARS-CoV infected and replicated more efficiently in Caco2 cells than in Calu3 cells under the same multiplicity of infection (p=0·0098). SARS-CoV-2, but not SARS-CoV, replicated modestly in U251 (neuronal) cells (p=0·036). For animal species cell tropism, both SARS-CoV and SARS-CoV-2 replicated in non-human primate, cat, rabbit, and pig cells. SARS-CoV, but not SARS-CoV-2, infected and replicated in Rhinolophus sinicus bat kidney cells. SARS-CoV-2 consistently induced significantly delayed and milder levels of cell damage than did SARS-CoV in non-human primate cells (VeroE6, p=0·016; FRhK4, p=0·0004). Interpretation: As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV. Funding: May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, Respiratory Viral Research Foundation, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, The Hong Kong Hainan Commercial Association South China Microbiology Research Fund, The Jessie & George Ho Charitable Foundation, Perfect Shape Medical, The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, The Theme-Based Research Scheme of the Research Grants Council, Sanming Project of Medicine in Shenzhen, and The High Level-Hospital Program, Health Commission of Guangdong Province, China.

The ability of a flexible pressure sensor to possess zero power consumption in standby mode, high sensitivity, and wide linear-response range is critical in real flexible matrix-based scenes. However, when the conventional flexible pressure sensors are attached on a curved surface, a pseudosignal response is generated because of the normal stress, resulting in a short linear-response range. Here, a flexible piezoresistive pressure sensor with high performance, zero standby power consumption is demonstrated. The flexible pressure sensor is fabricated from polydimethylsiloxane (PDMS)/carbon black (CB), patterned polyimide (PI) spacer layer, and laser-induced graphene (LIG) interdigital electrodes. Benefiting from the hierarchical structure and sufficient roughness of PDMS/CB and LIG interdigital electrodes, the proposed pressure sensors (PDMS/CB/PI/LIG) exhibit high sensitivity (43 kPa-1), large linear-response range (0.4-13.6 kPa), fast response (1800 cycles). The resulting pressure sensor also features zero standby power consumption merit under certain bending conditions (bending angle: 0-5o). Furthermore, the effect of the hole diameter of the PI spacer layer on the performance of the pressure sensors is experimentally and theoretically investigated. As a proof of concept, a bioinspired artificial haptic neuron system has been successfully equipped to modulate the number of lit LED lights. The proposed high-performance pressure sensor has promising potential to be used in flexible and wearable electronics, especially for the applications in actual flexible matrix-based scenes. Ministry of Education (MOE) This work was partially supported by the National Key R&D Program of China (2018YFB1500200), Shenzhen Basic Research Grant: JCYJ20180507182431967, JCYJ20170413153246713, Shenzhen Peacock Technology Innovation Project: KQJSCX20170731165602155, the National Nature Science Foundation of China (11804354, 61574157, 61774164). The authors are also grateful for the support of Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2015-T2-2-010), and Singapore Ministry of Education Academic Research Fund Tier 1 (MOE2019-T1-001-103).

Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90β, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90β interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90β is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.

Objectives: To evaluate the effects of mindfulness-based stress reduction (MBSR) combined with music therapy (MT) on clinical symptoms in patients with osteosarcoma. Methods: Patients diagnosed with osteosarcoma were assessed for eligibility. A total of 101 patients were ultimately randomized into the intervention and control groups. Both groups received routine care. Eight sessions of MBSR and MT psychotherapy were conducted in the intervention group, while the control group received no psychological intervention. Patients were assessed regarding pain, anxiety, and sleep quality at two distinct stages: before and after the intervention. Results: There were no significant differences in sociodemographic and clinical parameters between the intervention and control groups at baseline. The intervention program significantly alleviated psychological and physiological complications in patients with osteosarcoma. Specifically, the study revealed that 8 weeks of the combined MBSR/MT intervention effectively reduced pain and anxiety scores and improved the quality of sleep in patients. Conclusion: MBSR combined with MT significantly alleviated clinical symptoms, and could be considered a new, effective psychotherapeutic intervention for patients with osteosarcoma.