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.
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•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.
Abstract
Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of ...the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
Electrochemistry of hot electrons in fully aqueous solutions at tetrahedral amorphous carbon thin film electrodes is discussed. The generation of these highly reducing chemical species was confirmed ...by normal pulse voltammetry and several electrochemiluminescent systems. Electron transfer into pre‐existing solvent cavities was observed at approximately −2.65 V vs. Ag/AgCl (sat.). Electrogenerated hot electrons were utilized as chemiluminescent mediators in heterogeneous sandwich immunoassay of Serum Amyloid A. The calibration curve was linear over four orders of magnitude and the detection limit was 85 ng L−1 that demonstrates the efficiency of hot electron generation at this electrode material.
Perovskite oxides have received a great deal of attention as promising electrodes in both solid oxide fuel cells (SOFCs) and solid oxide electrolyzer cells (SOECs) because of their reasonable ...reactivity, impurity tolerance, and tunable properties. In particular, exploration is still required for improving perovskite electrodes, which normally suffer from slow kinetics in electrocatalysis. Experimental studies have led to the development of new classes of perovskites with advanced characteristics and electrode kinetics at technical levels. In parallel with those developments, achievements in theoretical and computational studies have led to substantial understanding, at the atomic level, of their physicochemical properties and electrocatalytic behaviors. Their chemical and structural flexibilities enable perovskites to accommodate most metallic elements without destroying their complex matrix structures, thereby delivering a pathway to engineer their catalytic properties. In this Minireview, recent advances in perovskite electrodes are introduced, and perovskites with exsolved nanoparticles are discussed as enhanced electrocatalytic materials.
Excellent exsolution: In this Minireview, perovskites with exsolved nanoparticles are examined as enhanced electrocatalytic materials for solid oxide cells. Nanoparticle exsolution is among the most promising techniques for future catalysis and energy technologies in sustainable systems. In light of its great advantages, this strategy has received much attention for developing suitable electrocatalysts for a wide range of applications.
In applying large-momentum effective theory, renormalization of the Euclidean correlators in lattice regularization is a challenge due to linear divergences in the self-energy of Wilson lines. Based ...on lattice QCD matrix elements of the quasi-PDF operator at lattice spacing a=0.03fm ∼ 0.12fm with clover and overlap valence quarks on staggered and domain-wall sea, we design a strategy to disentangle the divergent renormalization factors from finite physics matrix elements, which can be matched to a continuum scheme at short distance such as dimensional regularization and minimal subtraction. Our results indicate that the renormalization factors are universal in the hadron state matrix elements. Moreover, the physical matrix elements appear independent of the valence fermion formulations. These conclusions remain valid even with HYP smearing which reduces the statistical errors albeit reducing control of the renormalization procedure. Moreover, we find a large non-perturbative effect in the popular RI/MOM and ratio renormalization scheme, suggesting favor of the hybrid renormalization procedure proposed recently.
We present the first lattice-QCD calculation of the kaon distribution amplitude using the large-momentum effective theory (LaMET) approach. The momentum-smearing technique has been implemented to ...improve signals at large meson momenta. We subtract the power divergence due to Wilson line to high precision using multiple lattice spacings. The kaon structure clearly shows an asymmetry of the distribution amplitude around x=1/2, a clear sign of its skewness. Our result also prefers a broader distribution than the asymptotic form. We also study the leading SU(3) flavor symmetry breaking relations for the pion, kaon and eta meson distribution amplitudes, and the results are consistent with the prediction from chiral perturbation theory.
Twenty-four PM2.5 samples were collected at a suburban site of Xinxiang during Chinese Spring Festival (SF) in 2015. 10 water-soluble ions, 19 trace elements and 8 fractions of carbonaceous species ...in PM2.5 were analyzed. Potential sources of PM2.5 were quantitatively apportioned using principal component analysis (PCA)-multivariate linear regressions (MLR). The threat of heavy metals in PM2.5 was assessed using incremental lifetime cancer risk (ILCR). During the whole period, serious regional haze pollution persisted, the average concentration of PM2.5 was 111±54μgm−3, with 95.8% and 79.2% of the daily samples exhibiting higher PM2.5 concentrations than the national air quality standard I and II. Chemical species declined due to holiday effect with the exception of K, Fe, Mg, Al and K+, Cl−, which increased on Chinese New Year (CNY)'s Eve and Lantern Festival in 2015, indicating the injection of firework burning particles in certain short period. PM2.5 mass closure showed that secondary inorganic species were the dominant fractions of PM2.5 over the entire sampling (37.3%). 72-hour backward trajectory clusters indicated that most serious air pollution occurred when air masses transported from the Inner Mongolia, Shanxi and Zhengzhou. Health risk assessment revealed that noncancerous effects of heavy metals in PM2.5 of Xinxiang were unlikely happened, while lifetime cancer risks of heavy metals obviously exceeded the threshold, which might have a cancer risk for residents in Xinxiang. This study provided detailed composition data and first comprehensive analysis of PM2.5 during the Spring Festival period in Xinxiang.
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•The effect of firecracker burning on PM2.5 characteristics and human health was assessed.•The burning of firecrackers elevated PM2.5 in a short time.•The burning of firecrackers changed the chemical compositions of PM2.5•PM2.5 concentrations differed for various air mass origins.•Lifetime cancer risks of heavy metals (6.54×10−5) obviously exceed the threshold (10−6).
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
To establish cost-efficient operating conditions for potential application of Fenton oxidation process to treat wastewater containing an azo dye Orange G (OG), some important operating parameters ...such as pH value of solutions, dosages of H
2O
2 and Fe
2+, temperature, presence/absence of chloride ion and concentration of the dye, which effect on the decolorization of OG in aqueous solution by Fenton oxidation have been investigated systematically. In addition, the decolorization kinetics of OG was also elucidated based on the experimental data. The results showed that a suitable decolorization condition was selected as initial pH 4.0, H
2O
2 dosage 1.0
×
10
−2
M and molar ratio of H
2O
2/Fe
2+ 286:1. The decolorization of OG enhanced with the increasing of reaction temperature but decreased as a presence of chloride ion. On the given conditions, for 2.21
×
10
−5 to 1.11
×
10
−4
M of OG, the decolorization efficiencies within 60
min were more than 94.6%. The decolorization kinetics of OG by Fenton oxidation process followed the second-order reaction kinetics, and the apparent activation energy
E, was detected to be 34.84
kJ
mol
−1. The results can provide fundamental knowledge for the treatment of wastewater containing OG and/or other azo dyes by Fenton oxidation process.
One of the main challenges for advanced metallic nanoparticles (NPs) supported functional perovskite catalysts is the simultaneous achievement of a high population of NPs with uniform distribution as ...well as long-lasting high performance. These are also the essential requirements for optimal electrode catalysts used in solid oxide fuel cells and electrolysis cells (SOFCs and SOECs). Herein, we report a facile operando manufacture way that the crystal reconstruction of double perovskite under reducing atmosphere can spontaneously lead to the formation of ordered layered oxygen deficiency and yield segregation of massively and finely dispersed NPs. The real-time observation of this emergent process was performed via an environmental transmission electron microscope. Density functional theory calculations prove that the crystal reconstruction induces the loss of coordinated oxygen surrounding B-site cations, serving as the driving force for steering fast NP growth. The prepared material shows promising capability as an active and stable electrode for SOFCs in various fuels and SOECs for CO2 reduction. The conception exemplified here could conceivably be extended to fabricate a series of supported NPs perovskite catalysts with diverse functionalities.
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