Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, ...and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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•CH25H and its enzymatic product, 25HC, inhibit ZIKV entry in vitro•25HC attenuates ZIKV-associated viremia and disease in mice and non-human primates•25HC prevents ZIKV infection in human cortical organoids•25HC protects fetal mice from microcephaly caused by ZIKV infection
Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.
The paper studies asynchronous consensus problems of continuous-time multi-agent systems with discontinuous information transmission. The proposed consensus control strategy is implemented based on ...the state information of each agent's neighbors at some discrete times. The asynchrony means that each agent's update times, at which the agent adjusts its dynamics, are independent of others'. Furthermore, it is assumed that the communication topology among agents is time-dependent and the information transmission is with bounded time-varying delays. If the union of the communication topology across any time interval with some given length contains a spanning tree, the consensus problem is shown to be solvable. The analysis tool developed in this paper is based on nonnegative matrix theory and graph theory. The main contribution of this paper is to provide a valid distributed consensus algorithm that overcomes the difficulties caused by unreliable communication channels, such as intermittent information transmission, switching communication topology, and time-varying communication delays, and therefore has its obvious practical applications. Simulation examples are provided to demonstrate the effectiveness of the theoretical results.
Supported metal nanoparticles are widely used as catalysts in the industrial production of chemicals, but still suffer from deactivation because of metal leaching and sintering at high temperature. ...In recent years, serious efforts have been devoted to developing new strategies for stabilizing metal nanoparticles. Recent developments for preparing sinter‐resistant metal‐nanoparticle catalysts via strong metal–support interactions, encapsulation with oxide or carbon layers and within mesoporous materials, and fixation in zeolite crystals, are briefly summarized. Furthermore, the current challenges and future perspectives for the preparation of highly efficient and extraordinarily stable metal‐nanoparticle‐based catalysts, and suggestions regarding the mechanisms involved in sinter resistance, are proposed.
Recent advancements in the design and application of sinter‐resistant metal nanoparticles are reviewed. Several strategies are proposed for stabilizing metal nanoparticle catalysts. The exciting progress of sinter‐resistant supported metal‐nanoparticle catalysts is achieved via various methodologies, including strong metal–support interactions, encapsulation with oxide or carbon layers and within mesoporous materials, and fixation in zeolite crystals.
Purpose
Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. ...Furthermore, the changes of gut microbiota in IBD’s patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD.
Methods
The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD’s remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described.
Results
Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD’s remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26,
P
< 0.05; SMD = 1.00, 95% CI 0.27, 1.73,
P
< 0.05). In subgroup analyses of IBD remission rate and UC disease activity index, we obtained some statistically significant results in some subgroup (
P
< 0.05). To some extent, probiotic supplements can increase the number of beneficial bacteria (especially
Bifidobacteria
) in the intestinal tract of patients with IBD.
Conclusions
Our results support the treatment of IBD (especially UC) with pro/pre/synbiotics, and synbiotics are more effective. Probiotic supplements that are based on
Lactobacillus
and
Bifidobacterium
or more than one strain are more likely to be beneficial for IBD remission. The dose of 10
10
–10
12
CFU/day may be a reference range for using probiotics to relieve IBD.
Restructuring-induced catalytic activity is an intriguing phenomenon of fundamental importance to rational design of high-performance catalyst materials. We study three copper-complex materials for ...electrocatalytic carbon dioxide reduction. Among them, the copper(II) phthalocyanine exhibits by far the highest activity for yielding methane with a Faradaic efficiency of 66% and a partial current density of 13 mA cm
at the potential of - 1.06 V versus the reversible hydrogen electrode. Utilizing in-situ and operando X-ray absorption spectroscopy, we find that under the working conditions copper(II) phthalocyanine undergoes reversible structural and oxidation state changes to form ~ 2 nm metallic copper clusters, which catalyzes the carbon dioxide-to-methane conversion. Density functional calculations rationalize the restructuring behavior and attribute the reversibility to the strong divalent metal ion-ligand coordination in the copper(II) phthalocyanine molecular structure and the small size of the generated copper clusters under the reaction conditions.
Thermal barrier coatings (TBCs) can effectively protect the alloy substrate of hot components in aeroengines or land-based gas turbines by the thermal insulation and corrosion/erosion resistance of ...the ceramic top coat. However, the continuous pursuit of a higher operating temperature leads to degradation, delamination, and premature failure of the top coat. Both new ceramic materials and new coating structures must be developed to meet the demand for future advanced TBC systems. In this paper, the latest progress of some new ceramic materials is first reviewed. Then, a comprehensive spalling mechanism of the ceramic top coat is summarized to understand the dependence of lifetime on various factors such as oxidation scale growth, ceramic sintering, erosion, and calcium-magnesium-aluminium-silicate (CMAS) molten salt corrosion. Finally, new structural design methods for high-performance TBCs are discussed from the perspectives of lamellar, columnar, and nanostructure inclusions. The latest developments of ceramic top coat will be presented in terms of material selection, structural design, and failure mechanism, and the comprehensive guidance will be provided for the development of next-generation advanced TBCs with higher temperature resistance, better thermal insulation, and longer lifetime.
The adsorption of molecules on metal nanoparticles can be sterically controlled through the use of zeolite crystals, which enhances the product selectivity in hydrogenations of reactants with more ...than one reducible group. Key to this success was the fixation of Pd nanoparticles inside Beta zeolite crystals to form a defined structure (Pd@Beta). In the hydrogenation of substituted nitroarenes with multiple reducible groups as a model reaction, the Pd@Beta catalyst exhibited superior selectivity for hydrogenation of the nitro group, outperforming both conventional Pd nanoparticles supported on zeolite crystals and a commercial Pd/C catalyst. The extraordinary selectivity of Pd@Beta was attributed to the sterically selective adsorption of the nitroarenes on the Pd nanoparticles controlled by the zeolite micropores, as elucidated by competitive adsorption and adsorbate displacement tests. Importantly, this strategy is general and was extended to the synthesis of selective Pt and Ru catalysts by fixation inside Beta and mordenite zeolites.
Pitaya‐like catalysts: Pd nanoparticles were fixed inside Beta zeolite crystals (Pd@Beta) to obtain a catalyst that displayed superior selectivity in the hydrogenation of substituted nitroarenes with multiple reducible groups. The high selectivity was attributed to the sterically controlled adsorption of the nitroarenes on the Pd nanoparticles within the zeolite micropores.
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.
Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought ...an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.
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•Human ACE2 knockin mice were generated by using CRISPR/Cas9 technology•SARS-CoV-2 leads to robust replication in lung, trachea, and brain•SARS-CoV-2 causes interstitial pneumonia and elevated cytokine in aged hACE2 mice•High dose of SARS-CoV-2 can establish infection via intragastric route in hACE2 mice
The COVID-19 pandemic has brought an urgent need for small animal models. Here, Sun et al. established an ACE2 humanized mouse by CRISPR/Cas9 knockin technology. These hACE2 mice are susceptible to SARS-CoV-2 infection upon intranasal inoculation, and the resulting pulmonary infection and pathological changes resemble those observed in COVID-19 patients.
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated ...multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution Ser139→Asn139 (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
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