Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. ...Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
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.
Despite wide applications of bimetallic electrocatalysis in oxygen evolution reaction (OER) owing to their superior performance, the origin of the improved performance remains elusive. The underlying ...mechanism was explored by designing and synthesizing a series of stable metal–organic frameworks (MOFs: NNU‐21–24) based on trinuclear metal carboxylate clusters and tridentate carboxylate ligands. Among the examined stable MOFs, NNU‐23 exhibits the best OER performance; particularly, compared with monometallic MOFs, all the bimetallic MOFs display improved OER activity. DFT calculations and experimental results demonstrate that introduction of the second metal atom can improve the activity of the original atom. The proposed model of bimetallic electrocatalysts affecting their OER performance can facilitate design of efficient bimetallic catalysts for energy storage and conversion, and investigation of the related catalytic mechanisms.
An iron atom in an Fe3 cluster is replaced by a second metal to form Fe2M clusters, which can serve as nodes to bridge with organic ligands and construct stable bimetallic MOFs. The introduction of the second metal atom can improve the activity of the original atom and thus improve the oxygen evolution reaction performance of electrocatalysts.
A strategy to covalently connect crystalline covalent organic frameworks (COFs) with semiconductors to create stable organic–inorganic Z‐scheme heterojunctions for artificial photosynthesis is ...presented. A series of COF–semiconductor Z‐scheme photocatalysts combining water‐oxidation semiconductors (TiO2, Bi2WO6, and α‐Fe2O3) with CO2 reduction COFs (COF‐316/318) was synthesized and exhibited high photocatalytic CO2‐to‐CO conversion efficiencies (up to 69.67 μmol g−1 h−1), with H2O as the electron donor in the gas–solid CO2 reduction, without additional photosensitizers and sacrificial agents. This is the first report of covalently bonded COF/inorganic‐semiconductor systems utilizing the Z‐scheme applied for artificial photosynthesis. Experiments and calculations confirmed efficient semiconductor‐to‐COF electron transfer by covalent coupling, resulting in electron accumulation in the cyano/pyridine moieties of the COF for CO2 reduction and holes in the semiconductor for H2O oxidation, thus mimicking natural photosynthesis.
Here comes the sun: A strategy to covalently connect covalent organic frameworks with semiconductors to create organic–inorganic Z‐scheme heterojunctions was developed and applied for the CO2 photoreduction with H2O. This work delivers new insights for the future design of Z‐scheme organic–inorganic heterojunctions for artificial photosynthesis.
Searching the cost‐effective organic semiconductors is strongly needed in order to facilitate the practice of organic solar cells (OSCs), yet to be fulfilled. Herein, we have succeeded in developing ...two non‐fused ring electron acceptors (NFREAs), leading to the highest efficiency of 16.2 % for the NFREA derived OSCs. These OSCs exhibit the superior operational stabilities under one sun equivalent illumination without ultraviolet (UV) filtration. It is revealed that the modulation of halogen substituents on aromatic side chains, as the new structural tool to tune the intermolecular interaction and optoelectronic properties of acceptors, not only promotes the interlocked tic‐tac‐toe frame of three‐dimensional stacks in solid, but also improves charge dynamics of acceptors to enable high‐performance and stable OSCs.
Two non‐fused ring electron acceptors (NFREAs) have been developed. The halogen substituents on the aromatic side chains, as the new structure design tools, not only facilitate the construction of 3D stacks in solid, but also optimize the optoelectronic properties of the NFREAs, leading to organic solar cells with 16.2 % efficiency and excellent operational stability.
Electrochemical water splitting is one of the most economical and sustainable methods for large-scale hydrogen production. However, the development of low-cost and earth-abundant non-noble-metal ...catalysts for the hydrogen evolution reaction remains a challenge. Here we report a two-dimensional coupled hybrid of molybdenum carbide and reduced graphene oxide with a ternary polyoxometalate-polypyrrole/reduced graphene oxide nanocomposite as a precursor. The hybrid exhibits outstanding electrocatalytic activity for the hydrogen evolution reaction and excellent stability in acidic media, which is, to the best of our knowledge, the best among these reported non-noble-metal catalysts. Theoretical calculations on the basis of density functional theory reveal that the active sites for hydrogen evolution stem from the pyridinic nitrogens, as well as the carbon atoms, in the graphene. In a proof-of-concept trial, an electrocatalyst for hydrogen evolution is fabricated, which may open new avenues for the design of nanomaterials utilizing POMs/conducting polymer/reduced-graphene oxide nanocomposites.
Zn‐based aqueous batteries have attracted much attention because of their high theoretical‐capacity, safety, and low‐cost, yet the H2‐evolution, qualification or inhibition mechanism investigations ...that are closely related to the dendrite‐growth are rare and challenging. Herein, a series of zincophilic metal‐covalent organic frameworks (e.g., Zn‐AAn‐COF, Zn‐DAAQ‐COF, and Zn‐DAA‐COF) have been explored as model‐platforms to manipulate the H2‐evolution and Zn2+ flux. Best of them, Zn‐AAn‐COF based cell only produces 0.002 mmol h−1 cm−2 H2, which is >2 orders of magnitude lower than bare Zn. Noteworthy, it affords high stability for 3000 cycles (overpotential, <79.1 mV) at 20 mA cm−2 in symmetric‐cell and enhanced cycling‐stability up to 6000 cycles at 2000 mA g−1 in the assembled full‐battery. Besides, mechanistic characterizations show that Zn‐AAn‐COF can enhance the energy‐barrier of H2‐evolution and homogenize the ion‐distribution or electric‐filed to achieve high performance.
A series of porous Zn‐COF@Zn anodes have been fabricated to synergistically manipulate the H2 evolution and Zn2+ flux, during which the closely related H2 qualification/inhibition and Zn dendrite‐growth in zinc‐based aqueous batteries have been studied.
Unprecedented measures have been adopted to control the rapid spread of the ongoing COVID-19 epidemic in China. People's adherence to control measures is affected by their knowledge, attitudes, and ...practices (KAP) towards COVID-19. In this study, we investigated Chinese residents' KAP towards COVID-19 during the rapid rise period of the outbreak. An online sample of Chinese residents was successfully recruited via the authors' networks with residents and popular media in Hubei, China. A self-developed online KAP questionnaire was completed by the participants. The knowledge questionnaire consisted of 12 questions regarding the clinical characteristics and prevention of COVID-19. Assessments on residents' attitudes and practices towards COVID-19 included questions on confidence in winning the battle against COVID-19 and wearing masks when going out in recent days. Among the survey completers (n=6910), 65.7% were women, 63.5% held a bachelor degree or above, and 56.2% engaged in mental labor. The overall correct rate of the knowledge questionnaire was 90%. The majority of the respondents (97.1%) had confidence that China can win the battle against COVID-19. Nearly all of the participants (98.0%) wore masks when going out in recent days. In multiple logistic regression analyses, the COVID-19 knowledge score (OR: 0.75-0.90, P<0.001) was significantly associated with a lower likelihood of negative attitudes and preventive practices towards COVID-2019. Most Chinese residents of a relatively high socioeconomic status, in particular women, are knowledgeable about COVID-19, hold optimistic attitudes, and have appropriate practices towards COVID-19. Health education programs aimed at improving COVID-19 knowledge are helpful for Chinese residents to hold optimistic attitudes and maintain appropriate practices. Due to the limited sample representativeness, we must be cautious when generalizing these findings to populations of a low socioeconomic status.
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