Exploring high‐efficiency and stable halide perovskite‐based photocatalysts for the selective reduction of CO2 to methane is a challenge because of the intrinsic photo‐ and chemical instability of ...halide perovskites. In this study, halide perovskites (Cs3Bi2Br9 and Cs2AgBiBr6) were grown in situ in mesoporous TiO2 frameworks for an efficient CO2 reduction. Benchmarked CH4 production rates of 32.9 and 24.2 μmol g−1 h−1 with selectivities of 88.7 % and 84.2 %, were achieved, respectively, which are better than most reported halide perovskite photocatalysts. Focused ion‐beam sliced‐imaging techniques were used to directly image the hyperdispersed perovskite nanodots confined in mesopores with tunable sizes ranging from 3.8 to 9.9 nm. In situ X‐ray photoelectronic spectroscopy and Kelvin probe force microscopy showed that the built‐in electric field between the perovskite nanodots and mesoporous titania channels efficiently promoted photo‐induced charge transfer. Density functional theory calculations indicate that the high methane selectivity was attributed to the Bi‐adsorption‐mediated hydrogenation of *CO to *HCO that dominates CO desorption.
Halide perovskites (Cs3Bi2Br9, Cs2AgBiBr6) are grown in situ in a mesoporous titania framework for efficient CO2 reduction reaction (CO2RR). A benchmarked production rate of CH4 (32.9 and 24.2 μmol g−1 h−1) is achieved with selectivity values of 88.7 % and 84.2 %, respectively. In situ X‐ray photoelectronic spectroscopy and Kelvin probe force microscopy reveal that the inner surface built‐in electric field between the perovskite nanodots and mesoporous titania channels can efficiently promote photo‐induced charge transfer.
Fibrosis serves a critical role in driving atrial remodelling‐mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with ...cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang‐II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up‐regulated in the Ang‐II‐induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF‐β1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang‐II were significantly higher in the Ang‐II‐induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF‐β1/Smads signalling pathway) diminished these Ang‐II‐mediated effects, and the si‐Smad3‐mediated effects were, in turn, antagonized by the addition of a PU.1‐overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang‐II and attenuated vulnerability to AF, at least in part through the TGF‐β1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang‐II‐induced atrial fibrosis and vulnerability to AF.
The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI ...symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics.
COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province.
Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m
A methylation and changed binding capacity with ACE2.
We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.
Cyanobacterial harmful algal blooms (cyanoHABs) in freshwater lakes across the globe are often combined with other stressors. Pharmaceutical pollution, especially antibiotics in water bodies, poses a ...potential hazard in aquatic ecosystems. However, how antibiotics influence the risk of cyanoHABs remains unclear. Here, we investigated the effects of norfloxacin (NOR), one of the most widely used antibiotics globally, to a bloom‐forming cyanobacterium (Microcystis aeruginosa) and a common green alga (Scenedesmus quadricauda), under both mono‐ and coculture conditions. Taxon‐specific responses to NOR were evaluated in monoculture. In addition, the growth rate and change in ratio of cyanobacteria to green algae when cocultured with exposure to NOR were determined. In monocultures of Microcystis, exposure to low concentrations of NOR resulted in decreases in biomass, chlorophyll a and soluble protein content, while superoxide anion content and superoxide dismutase activity increased. However, NOR at high concentration only slightly affected Scenedesmus. During the co‐culture trials of Microcystis and Scenedesmus, the 5 μg · L−1 NOR treatment increased the ratio of Microcystis to co‐cultured Scenedesmus by 47.2%. Meanwhile, although Scenedesmus growth was enhanced by 4.2% under NOR treatment in monoculture, it was conversely inhibited by 63.4% and 38.2% when co‐cultured with Microcystis with and without NOR, respectively. Our results indicate that antibiotic pollution has a potential risk to enhance the perniciousness of cyanoHABs by disturbing interspecific interaction between cyanobacteria and green algae. These results reinforce the need for scientists and managers to consider the influence of xenobiotics in shaping the outcome of interactions among multiple species in aquatic ecosystems.
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.
Chemotherapy for non‐small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self‐adaptations of the tumors. Angiogenesis, vasculogenic mimicry ...(VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV‐modified epirubicin and dioscin co‐delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM‐related and angiogenesis‐related proteins in vitro. Furthermore, when tested in vivo, the targeted co‐delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV‐modified epirubicin and dioscin co‐delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.
Targeted epirubicin and dioscin co‐delivery liposomes modified with RPV increased cellular uptake and accumulation in the A549 cells. The RPV‐modified epirubicin and dioscin co‐delivery liposomes enhanced anti‐tumor efficacy in vitro and in vivo. The RPV‐modified epirubicin and dioscin co‐delivery liposomes inhibited NSCLC migration and invasion by limiting tumor angiogenesis and vasculogenic mimicry formation.
Delayed neurologic sequelae (DNS) are among the most serious complications of carbon monoxide (CO) poisoning caused partly by elevated neuroinflammation. WIN 55,212-2, a non-selective agonist of ...cannabinoid receptors, has been demonstrated to have anti-inflammatory properties in various brain disorders. The anti-inflammatory action of WIN 55,212-2 is potentially associated with driving microglial M2 polarization. ST2 signaling is important in regulating inflammatory responses and microglial polarization. Therefore, we aimed to investigate the neuroprotective effect of WIN 55,212-2 on DNS after CO poisoning and elucidate its relationship with ST2-mediated microglial M2 polarization. The behavioral tests showed that treatment with WIN 55,212-2 significantly ameliorates the cognitive impairment induced by CO poisoning. This behavioral improvement was accompanied by reduced neuron loss, decreased production of pro-inflammatory cytokines, and a limited number of microglia in the hippocampus. Moreover, WIN 55,212-2 elevated the protein expression of IL-33 (the ligand of ST2) and ST2, increased the ratio of CD206-positive (M2 phenotype) and ST2-positive microglia, and augmented production of M2 microglia-associated cytokines in the hippocampus of CO-exposed rats. Furthermore, we observed that the WIN 55,212-2-mediated increases in ST2 protein expression, CD206-positive and ST2-positive microglia, and microglia-associated cytokines were blocked by the cannabinoid receptor 2 (CB2R) antagonist AM630 but not by the cannabinoid receptor 1 (CB1R) antagonist AM251. In contrast, the WIN 55,212-2-induced upregulation of the IL-33 protein expression was inhibited by AM251 but not by AM630. Altogether, these findings reveal cannabinoid receptors as promising therapeutic agents for CO poisoning and identify ST2 signaling-related microglial M2 polarization as a new mechanism of cannabinoid-induced neuroprotection.
In this paper, a comprehensive theory for wavelength modulation laser heterodyne spectroscopy is presented. Some necessary simplifications based on the Taylor series are introduced, the general ...formulas employed to demodulate the first harmonic signal (1f), the second harmonic signal (2f), and higher harmonic signal (nf) are derived in details, and hence the formulas are suitable for an arbitrary intensity modulation amplitude and modulation index. The purpose of this paper: an overview of how the laser heterodyne harmonic signal depends on the experimental parameters of intensity modulation amplitude and modulation index is reported. This overview is helpful to choose these parameters for the best laser heterodyne harmonic signal because it initiated a new pathway for systematically analyzing the relationships between the experimental parameters and the laser heterodyne harmonic signal.