This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an ...appropriate dose of the candidate vaccine for an efficacy study.
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
The shortage of groundwater resources is a considerable challenge for winter wheat production on the North China Plain. Water-saving technologies and procedures are thus urgently required. To ...determine the water-saving potential of using micro-sprinkling irrigation (MSI) for winter wheat production, field experiments were conducted from 2012 to 2015. Compared to traditional flooding irrigation (TFI), micro-sprinkling thrice with 90 mm water (MSI1) and micro-sprinkling four times with 120 mm water (MSI2) increased the water use efficiency by 22.5 and 16.2%, respectively, while reducing evapotranspiration by 17.6 and 10.8%. Regardless of the rainfall pattern, MSI (i.e., MSI1 or MSI2) either stabilized or significantly increased the grain yield, while reducing irrigation water volumes by 20–40%, compared to TFI. Applying the same volumes of irrigation water, MSI (i.e., MSI3, micro-sprinkling five times with 150 mm water) increased the grain yield and water use efficiency of winter wheat by 4.6 and 11.7%, respectively, compared to TFI. Because MSI could supply irrigation water more frequently in smaller amounts each time, it reduced soil layer compaction, and may have also resulted in a soil water deficit that promoted the spread of roots into the deep soil layer, which is beneficial to photosynthetic production in the critical period. In conclusion, MSI1 or MSI2 either stabilized or significantly increased grain yield while reducing irrigation water volumes by 20–40% compared to TFI, and should provide water-saving technological support in winter wheat production for smallholders on the North China Plain.
Plant neighbor detection and response strategies are important mediators of interactions among species. Despite increasing knowledge of neighbor detection and response involving plant volatiles, less ...is known about how soil-borne signaling chemicals may act belowground in plant-plant interactions. Here, we experimentally demonstrate neighbor detection and allelopathic responses between wheat and 100 other plant species via belowground signaling. Wheat can detect both conspecific and heterospecific neighbors and responds by increasing allelochemical production. Furthermore, we show that (-)-loliolide and jasmonic acid are present in root exudates from a diverse range of species and are able to trigger allelochemical production in wheat. These findings suggest that root-secreted (-)-loliolide and jasmonic acid are involved in plant neighbor detection and allelochemical response and may be widespread mediators of belowground plant-plant interactions.
Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought ...to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.
Natural antioxidants are widely distributed in food and medicinal plants. These natural antioxidants, especially polyphenols and carotenoids, exhibit a wide range of biological effects, including ...anti-inflammatory, anti-aging, anti-atherosclerosis and anticancer. The effective extraction and proper assessment of antioxidants from food and medicinal plants are crucial to explore the potential antioxidant sources and promote the application in functional foods, pharmaceuticals and food additives. The present paper provides comprehensive information on the green extraction technologies of natural antioxidants, assessment of antioxidant activity at chemical and cellular based levels and their main resources from food and medicinal plants.
We report herein the first example of interpenetration isomerism in covalent organic frameworks (COFs). As a well-known three-dimensional (3D) COF, COF-300 was synthesized and characterized by the ...Yaghi group in 2009 as a 5-fold interpenetrated diamond structure ( dia-c5 topology). We found that adding an aging process prior to the reported synthetic procedure afforded the formation of an interpenetration isomer, dia-c7 COF-300. The 7-fold interpenetrated diamond structure of this new isomer was identified by powder X-ray diffraction and rotation electron diffraction analyses. Furthermore, we proposed a universal formula to accurately determine the number of interpenetration degrees of dia -based COFs from only the unit cell parameters and the length of the organic linker. This work not only provides a novel example to the category of interpenetration isomerism but also provides new insights for the further development of 3D COFs.
The development of new and highly efficient strategies for the rapid construction of complicated molecular structures has huge implications and remains a preeminent goal in present day synthetic ...chemistry. In the past ten years, visible light promoted aerobic oxidations have been emerging as one of the fastest growing fields in organic chemistry because of their low cost, easy availability and environmental friendliness. This review describes and highlights the scope and limitations, recent research progress in novel methodology development, and applications in organic synthesis, as well as the mechanisms of these visible light promoted aerobic oxidation reactions. The discussion contains several sections based on the following reaction types: (1) alcohols to aldehydes; (2) amines to nitriles; (3) methylarenes to aldehydes; (4) boronic acids to phenols; (5) formation of carbonyl compounds or ketones; (6) β-keto sulfones; (7) sulfoxides; (8) amine to amide; and (9) some other reactions.
The development of new and highly efficient strategies for the rapid construction of complicated molecular structures has huge implications and remains a preeminent goal in present day synthetic chemistry.
Summary Background A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy ...Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose. Methods We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone–China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18–50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 1011 viral particles), low-dose vaccine (8·0 × 1010 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed. Findings During Oct 10–28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 26% in high-dose group and 31 25% in low-dose group) than in those receiving placebo (17 14%; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 95% CI 976·6–1602·5 in low-dose group and 1728·4 1459·4–2047·0 in high-dose group) and peaked at day 28 (1471·8 1151·0–1881·8 and 2043·1 1762·4–2368·4), but declined quickly in the following months (223·3 148·2–336·4 and 254·2 185·0–349·5 at day 168). Geometric mean titres in the placebo group remained around 6·0–6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine. Interpretation The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 1010 viral particles was the optimal dose. Funding Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase ...separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, N
exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.
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