The weldability of a low-carbon copper-bearing age hardening steel was evaluated using cracking suscepti- bility calculation, HAZ maximum hardness measurement, and Y-groove cracking evaluation test. ...The results show that the hardenability characteristics and cold cracking susceptibility of the steel are very low. The results also indicate that a crack-free weldment can be obtained during the welding of this type of steel even at an ambient temperature as low as -5 ℃ as well as in an absolute humidity lower than 4 000 Pa without any preheat treatment. A slight preheat treatment can prevent the joint from cracking when welding is carried out at lower ambient temperature or higher absolute humidity.
Thallium (TI) is a kind of emerging contaminant with strong toxicity. In this study, a low-cost, renewable, biologically low-toxic and environmentally friendly fly ash/chitosan (FACS) composite ...adsorption material was synthesized by combining the characteristics of chitosan and fly ash to remove thallium from wastewater. SEM, FTIR and XRD analyses showed that the adsorbent mainly contained silicate compounds, and the surface of the particles contained a large number of micro porous structures. The adsorption process was rapid, reaching the adsorption equilibrium after 60min. When the pH value was 8, FACS had the best adsorption effect on TI, which was not conducive to the adsorption of TI in either strong acid or strong base environment. The co-existence of Fe3+ and Mn2+ could facilitate the adsorption of TI by FACS. The adsorption isotherm data were better fitted for the Freundlich model, while the Second-order kinetic model was more suitable for describing the kinetic data. Since the main chemical bond composition and chemical groups of FACS would not change after the adsorption of TI, the removal rate of TI was still high when it was reused after desorption. Because of its simple operation, low cost and reusability, FACS is considered to have certain potential in the removal of TI from wastewater.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical ...isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
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.
Display omitted
•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.
There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory ...symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.
Abstract
A Fourier transform spectrometer (FTS) has been used to observe solar activities due to its ultra-high spectral resolution. However, the FTS in-band spectra are usually distorted and some ...artifacts appear in out-of-band regions due to nonlinear effects. Therefore, the FTS nonlinear problem must be corrected. In this study, we proposed a novel method to correct the nonlinear effects using simulated annealing. We simulated several nonlinear spectra to evaluate the performance of our method. The calculated quadratic coefficients are extremely close to the given values, demonstrating that the method is effective and accurate. The proposed method is further used to correct the blackbody and solar spectra with nonlinearity obtained by Bruker IFS-125HR installed at the Huairou Solar Observing Station, which is a pathfinder for the accurate infrared magnetic field measurements of the Sun project. To the blackbody spectra, the nonlinearity in low- and high-frequency regions are corrected by 89.09% and 60.84%. The nonlinear correction of the solar spectra in the low- and high-frequency regions have reached 65.34% and 81.04%, respectively. These results prove that our method can correct the nonlinear problem to improve the data accuracy.
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel ...variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS‐CoV‐2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell‐specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco‐2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22,995 and 28,866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS‐CoV‐2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS‐CoV‐2 viruses, as well as a model for investigating SARS‐CoV‐2 recombination.
Zika virus (ZIKV) is primarily transmitted to humans through mosquito bites or sexual contact. The excretion and persistence of contagious ZIKV in various body fluids have been well documented in ...ZIKV patients; however, the risk of direct contact exposure remains unclear. Here, we show that guinea pigs are susceptible to ZIKV infection via subcutaneous inoculation route; infected guinea pigs exhibit seroconversion and significant viral secretion in sera, saliva, and tears. Notably, ZIKV is efficiently transmitted from infected guinea pigs to naïve co-caged animals. In particular, intranasal inoculation of ZIKV is fully capable of establishing infection in guinea pigs, and viral antigens are detected in multiple tissues including brain and parotid glands. Cynomolgus macaques also efficiently acquire ZIKV infection via intranasal and intragastric inoculation routes. These collective results from animal models highlight the risk of exposure to ZIKV contaminants and raise the possibility of close contact transmission of ZIKV in humans.
PDF
