Summary Background A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody ...persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. Methods We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6–35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov , number NCT01508247. Findings 10 245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1–96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2–90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). Interpretation EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. Funding China's 12–5 National Major Infectious Disease Program, Beijing Vigoo Biological.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has ...been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-associated HCCs, which accelerates high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity. Mechanistically, CD36-mediated oxLDL uptake triggers CEBPβ expression to directly upregulate Nogo-B, which interacts with ATG5 to promote lipophagy leading to lysophosphatidic acid-enhanced YAP oncogenic activity. This CD36-Nogo-B-YAP pathway consequently reprograms oxLDL metabolism and induces carcinogenetic signaling for NAFLD-associated HCCs. Targeting the Nogo-B pathway may represent a therapeutic strategy for HCC arising from the metabolic syndrome.
Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial ...resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.
Summary Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family ...Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia , and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.
Background
The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone‐acetyltransferase (HAT) activities are required in gene transcription of a ...large number of molecules in the immune system of the body.
Objectives
This study tests a hypothesis that HAT Tat‐interactive protein 60 (Tip60) plays an important role in the initiation of IgE‐mediated allergy.
Methods
The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE‐mediated allergic inflammation.
Results
High levels of Tip60 were observed in the peripheral B cells of patients with FA. Tat‐interactive protein 60 (Tip60) was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6), and nuclear factor‐κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa.
Conclusions
Tat‐interactive protein 60 (Tip60) plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti‐allergy drug.
Abstract Background The incidence of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis has increased significantly in China. Information ...about the susceptibility or potential of autoimmune diseases in the general population is lacking. Objective To explore the prevalence of antinuclear antibody (ANA) and its specificities in the general population in China. Methods Twenty thousand nine hundred seventy sera samples were taken from the physical examination center in Baoding, China. Indirect immunofluorescence and line immunoassays were used to detect ANA and its specificities, respectively. Results Samples from females had a higher prevalence of ANA than samples from males (χ2 = 278.55; P < 0.01). For both sexes, the prevalence of ANA positively correlated with age and there were significant differences among different age groups at 10-year intervals, except the 80 years group ( P < 0.05). One thousand two hundred forty-three ANA-positive samples were further analyzed with line immunoassays. There was a significant difference among age groups and between sex groups in terms of the specific autoantibodies ( P < 0.01). The autoantibodies with the top-3 positive frequencies were anti-Ro-52, anti-M2, and anti-SSA. Conclusions There was a high prevalence of ANA positivity in the general Chinese population that seemed to be influenced by sex and age and correlated with specific autoantibodies.
Topological semimetals host electronic structures with several band-contact points or lines and are generally expected to exhibit strong topological responses. Up to now, most work has been limited ...to non-magnetic materials and the interplay between topology and magnetism in this class of quantum materials has been largely unexplored. Here we utilize theoretical calculations, magnetotransport and angle-resolved photoemission spectroscopy to propose Fe
GeTe
, a van der Waals material, as a candidate ferromagnetic (FM) nodal line semimetal. We find that the spin degree of freedom is fully quenched by the large FM polarization, but the line degeneracy is protected by crystalline symmetries that connect two orbitals in adjacent layers. This orbital-driven nodal line is tunable by spin orientation due to spin-orbit coupling and produces a large Berry curvature, which leads to a large anomalous Hall current, angle and factor. These results demonstrate that FM topological semimetals hold significant potential for spin- and orbital-dependent electronic functionalities.
Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin ...of cosmological FRBs is still not settled. Here we report the detection of1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.9). These observations show irregular short-time variation ofthe Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth-Sun distance) ofthe source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.
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