Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19 (coronavirus disease 2019), which was first reported in Wuhan, China, in December 2019. Despite ...extensive efforts to control the disease, COVID-19 has now spread to more than 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are unknown. In this study, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Additionally, cats are susceptible to airborne transmission. Our study provides insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control.
An outbreak of coronavirus disease 2019 (COVID-19)
, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, has spread globally. Countermeasures are needed to treat and prevent ...further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern
. ...Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)
. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
The newly-emerging Middle East respiratory syndrome coronavirus （MERS-CoV） can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated ...pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vac- cines are not yet available. Using the spike receptor-binding domain of MERS-CoV （MERS-RBD） to immunize mice, we identified two neutralizing monoclonal antibodies （mAbs） 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crys- tallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-resi- due competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 （4C2h） antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings.
Conducting polymer-based composite aerogel film is desired to be used as thermoelectric (TE) materials due to its good flexibility and ultralow thermal conductivity. Here, we proposed the simple ...freeze drying method to fabricate free-standing poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS)-based aerogel films without any crosslinker addition. The evolutions of morphology and TE performance were systemically investigated with various organic solvent addition. Furthermore, a series of the PEDOT:PSS/tellurium nanowires (Te-NWs) composite aerogel films was prepared, and the relationship between the structure and the charge-transport mechanism of the binary complex system was explored based on series and parallel models. Finally, an efficient dimethyl sulfoxide-vapor annealing was employed to further optimize the TE performance of PEDOT:PSS/Te-NWs composite aerogel films. The ZT value was estimated to be 2.0 × 10–2 at room temperature. On the basis of the flexibility and highly enhanced TE performance, a prototype TE generator consisting of p-type PEDOT:PSS/Te-NWs aerogel films and n-type carbon nanotube fibers as legs has been fabricated with an acceptable output power of 1.28 μW at a temperature gradient of 60 K, which could be potentially applied in wearable electronics.
•Sub-region division for the multi-physics laser ultrasonic simulation.•Experimental validation using an noncontact laser measurement system.•Simulated micro crack detection using an nonlinear ...feature BD.•Parameter investigation for nonlinear feature BD.
Laser ultrasonic techniques have been widely investigated due to its high spatial resolution and capacity for remote and noncontact measurement. In this study, the laser induced ultrasonic wave on an aluminum plate is simulated, and a nonlinear feature is used to detect a micro crack introduced in the plate model. A multi-physics simulation is conducted and optimized considering the effect of thermal diffusion. A nonlinear feature, called Bhattacharyya Distance (BD), is calculated to show the crack-induced geometric difference among the state space attractors obtained from closely spaced measurement points near the crack. First, a 3D model is built, and its simulation result is compared with an experiment performed using a noncontact laser ultrasonic measurement system. Then, by creating a micro crack in the model, BD is extracted and the crack is successfully detected and visualized. Finally, the effects of BD parameters, such as embedding dimension and frequency band, on damage visualization are investigated.
Nonlinear wave modulation spectroscopy (NWMS) has been used to detect nonlinear ultrasonic signatures produced by fatigue cracks in materials. It is done by generating ultrasonic waves at two ...different frequencies and measuring their modulation. A proper choice of two distinct frequencies for a given structure plays a significant role in NWMS. This paper, instead of using input signals at two distinct frequencies, takes only one broadband pulse signal as the driving input, which can be generated by a laser beam. With a broadband excitation, material nonlinearity exhibits modulation at multiple peaks in a spectral plot due to interactions among various input frequency components of the broadband input. A feature called sideband peak count (SPC), which is defined as the ratio of the number of sideband (modulation) peaks over a moving threshold to the total peak number in the specified frequency band, is extracted from the spectral plot to measure the degree of material nonlinearity. The basic premise of the proposed laser nonlinear wave modulation spectroscopy (LNWMS) is that this SPC value will rise as the level of material nonlinearity increases. A noncontact laser ultrasonic system has been built for LNWMS measurement by integrating and synchronizing a Q-switched Nd:YAG laser for ultrasonic wave generation and a laser Doppler vibrometer for ultrasonic wave detection. The proposed LNWMS technique has been successfully tested for detecting fatigue cracks in metallic plates and aircraft fitting-lugs having complex geometries.
Coronavirus disease 2019 (COVID-19) pandemic has spread in 220 countries/regions to wreak havoc to human beings around the world. At present, the second wave of COVID-19 has begun in many European ...countries. The complete control of COVID-19 is very urgent. Although China quickly brought the virus under control, there have been eight sporadic outbreaks in China since then. Both in Xinfadi of Beijing and Dalian outbreak of COVID-19, environmental swab samples related to imported cold chain food were tested nucleic acid positive for SARS-CoV-2. In this outbreak in Qingdao, we directly isolated SARS-CoV-2 from the cod outer package's surface swab samples. This is the first time worldwide, SARS-CoV-2 were isolated from the imported frozen cod outer package's surface, which showed that imported frozen food industry could import SARS-CoV-2 virus.
•Fifty out of 421 cod outer package's surface swab samples were tested SARS-CoV-2 nucleic acid positive.•SARS-CoV-2 was isolated successfully as CPE were observed and the whole-genome sequence was achieved.•SARS-CoV-2 resulted in the outbreak in Qingdao felled in a European branch, which originated in Europe.
In this work, a sensitive photoelectrochemical aptasensor was developed for kanamycin detection using an enhanced photocurrent response strategy, which is based on the surface plasmon resonance ...effect of gold nanoparticles deposited on a 3D TiO2-MoS2 flower-like heterostructure. A significant aspect of this development lies in the photoelectrochemical and morphological features of the unique ternary composite, which have contributed to the excellent performance of the sensor. To develop an aptasensor, mercapto-group modified aptamers were immobilised on the photoactive composite as a recognition unit for kanamycin. The TiO2-MoS2-AuNP composite was demonstrated to accelerate the electron transfer, increase the loading of aptamers and improve the visible light excitation of the sensor. Under optimal conditions, the aptasensor exhibited a dynamic range from 0.2 nM to 450 nM of kanamycin with a detection limit of 0.05 nM. Overall, we have successfully synergised both the electrical and the optical merits from individual components to form a ternary composite, which was then demonstrated as an effective scaffold for the development of PEC biosensors.
•A photoelectrochemical biosensor consisting of a TiO2-MoS2-gold nanoparticle nanocomposite is excitable by visible light.•The nanocomposite demonstrates a large surface area and high conductivity.•A kanamycin photoelectrochemical aptasensor is developed based on the nanocomposite.•Sensitive kanamycin detection was achieved using an enhanced photocurrent response strategy.
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