The significant worldwide effects of Coronavirus disease 2019 (COVID-19) have been apparent since its outbreak. This unprecedentedly widespread virus, SARS-CoV-2, has high infectivity, asymptomatic ...transmission, and a long-term incubation period. These characteristics have led to the rapid spread of viruses between cities and humans. The cause of the outbreak of the epidemic in Wuhan is also due to the large population, transportation, and the healthcare system lack of public health prevention and intervention in Wuhan. This unavoidable pandemic not only because the virus has robust transmission, but also the city of Wuhan did not control the spread of the virus in the early stage of the epidemic. These factors lead to a huge public health problem worldwide.
Abstract
Exosomes, which are nanosized endocytic vesicles that are secreted by most cells, contain an abundant cargo of different RNA species that can modulate the behavior of recipient cells and may ...be used as circulating biomarkers for diseases. Here, we develop a web-accessible database (http://www.exoRBase.org), exoRBase, which is a repository of circular RNA (circRNA), long non-coding RNA (lncRNA) and messenger RNA (mRNA) derived from RNA-seq data analyses of human blood exosomes. Experimental validations from the published literature are also included. exoRBase features the integration and visualization of RNA expression profiles based on normalized RNA-seq data spanning both normal individuals and patients with different diseases. exoRBase aims to collect and characterize all long RNA species in human blood exosomes. The first release of exoRBase contains 58 330 circRNAs, 15 501 lncRNAs and 18 333 mRNAs. The annotation, expression level and possible original tissues are provided. exoRBase will aid researchers in identifying molecular signatures in blood exosomes and will trigger new exosomal biomarker discovery and functional implication for human diseases.
N6-methyladenosine (m6A) is the most abundant RNA modification in mammalian cells and the best-studied epitranscriptomic mark. Despite the development of various tools to map m6A, a ...transcriptome-wide method that enables absolute quantification of m6A at single-base resolution is lacking. Here we use glyoxal and nitrite-mediated deamination of unmethylated adenosines (GLORI) to develop an absolute m6A quantification method that is conceptually similar to bisulfite-sequencing-based quantification of DNA 5-methylcytosine. We apply GLORI to quantify the m6A methylomes of mouse and human cells and reveal clustered m6A modifications with differential distribution and stoichiometry. In addition, we characterize m6A dynamics under stress and examine the quantitative landscape of m6A modification in gene expression regulation. GLORI is an unbiased, convenient method for the absolute quantification of the m6A methylome.The m6A modification is mapped transcriptome-wide at single-base resolution in mammalian cells.
In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not ...all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) constitute the second wave of immunotherapy targets that show great promise for use in the treatment of solid tumors and leukemia. To promote the research and clinical application of ICBs directed at these targets, we summarize their discovery, immunotherapy mechanism, preclinical efficiency, and clinical trial results in this review.
Electroencephalogram (EEG) based brain-computer interfaces (BCI) in motor imagery (MI) have developed rapidly in recent years. A reliable feature extraction method is essential because of a low ...signal-to-noise ratio (SNR) and time-dependent covariates of EEG signals. Because of efficient application in various fields, deep learning has been adopted in EEG signal processing and has obtained competitive results compared with the traditional methods. However, designing and training an end-to-end network to fully extract potential features from EEG signals remains a challenge in MI.
In this study, we propose a parallel multiscale filter bank convolutional neural network (MSFBCNN) for MI classification. We introduce a layered end-to-end network structure, in which a feature-extraction network is used to extract temporal and spatial features. To enhance the transfer learning ability, we propose a network initialization and fine-tuning strategy to train an individual model for inter-subject classification on small datasets. We compare our MSFBCNN with the state-of-the-art approaches on open datasets.
The proposed method has a higher accuracy than the baselines in intra-subject classification. In addition, the transfer learning experiments indicate that our network can build an individual model and obtain acceptable results in inter-subject classification. The results suggest that the proposed network has superior performance, robustness, and transfer learning ability.
Porcine epidemic diarrhea virus (PEDV) has catastrophic impacts on the global pig industry. Although the fecal-oral route is generally accepted, an increased number of reports indicate that airborne ...transmission may contribute to PEDV outbreak. Here, we show that PEDV could cause typical diarrhea in piglets through a nasal spray. Firstly, PEDV can develop a transient nasal epithelium infection. Subsequently, PEDV-carrying dendritic cells (DCs) allow the virus to be transferred to CD3
T cells via the virological synapse. Finally, virus-loaded CD3
T cells reach the intestine through the blood circulation, leading to intestinal infection via cell-to-cell contact. Our study provides evidence for airborne transmission of a gastrointestinal infected coronavirus and illustrates the mechanism of its transport from the entry site to the pathogenic site.
Because membrane fusion is a crucial step in the process by which enveloped viruses invade host cells, membrane fusion inhibitors can be effective drugs against enveloped viruses. We found that ...surfactin from
can suppress the proliferation of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) in epithelial cells at a relatively low concentration range (15 to 50 μg/ml), without cytotoxicity or viral membrane disruption. Membrane fusion inhibition experiments demonstrate that surfactin treatment significantly reduces the rate at which the virus fuses to the cell membrane. Thermodynamic experiments show that the incorporation of small amounts of surfactin hinders the formation of negative curvature by lamellar-phase lipids, suggesting that surfactin acts a membrane fusion inhibitor. A fluorescent lipopeptide similar to surfactin was synthesized, and its ability to insert into the viral membrane was confirmed by spectroscopy.
experiments have shown that oral administration of surfactin to piglets protects against PEDV infection. In conclusion, our study indicates that surfactin is a membrane fusion inhibitor with activity against enveloped viruses. As the first reported naturally occurring wedge lipid membrane fusion inhibitor, surfactin is likely to be a prototype for the development of a broad range of novel antiviral drugs.
Membrane fusion inhibitors are a rapidly emerging class of antiviral drugs that inhibit the infection process of enveloped viruses. They can be classified, on the basis of the viral components targeted, as fusion protein targeting or membrane lipid targeting. Lipid-targeting membrane fusion inhibitors have a broader antiviral spectrum and are less likely to select for drug-resistant mutations. Here we show that surfactin is a membrane fusion inhibitor and has a strong antiviral effect. The insertion of surfactin into the viral envelope lipids reduces the probability of viral fusion. We also demonstrate that oral administration of surfactin protects piglets from PEDV infection. Surfactin is the first naturally occurring wedge lipid membrane fusion inhibitor that has been identified and may be effective against many viruses beyond the scope of this study. Understanding its mechanism of action provides a foundation for the development of novel antiviral agents.
Display omitted
•Analyzing intellectual property cooperation mechanism among heterogeneous entities.•GIUR intellectual property cooperation under two types of scenarios is introduced.•Evolutionary ...game modeling of GIUR intellectual property cooperation is proposed.•Giving the simulation results of GIUR intellectual property cooperation behavior.
Intellectual property cooperation is vital to integrating innovation resources, improving innovation energy. It involves many factors including behavioral agents and national economy-macro-management scenarios, should be seriously considered by multi-stakeholders during the process of intellectual property cooperation. Based on the evolutionary game theory, this paper analyzes the Government-Industry-University-Research (GIUR) intellectual property cooperation behavior and its influencing factors from market mechanism and administrative supervision mechanism. Firstly, the newly proposed game models are developed to observe the cooperation behavior which can be realized as strategies and payoff functions of the multi-stakeholders, then, the evolutionary replication dynamics equations are formulated to study evolutionarily stable strategies of multi-stakeholders. Finally, to verify the theoretical results, simulation experiments are conducted with meaningful results: under the market mechanism, the reasonable government subsidy incentive, and the liquidated damages can make GIUR practice an active intellectual property cooperation behavior to each other; under the administrative supervision mechanism, reasonable tax rate and administrative penalties are conducive to promoting and stabilizing GIUR intellectual property cooperation. In addition, the government will have the “interest appeal” to maximize additional social benefits in the game with enterprises, universities or research institutes. The results can guide GIUR to make better decisions in the future.
Ultrastrong bioinspired graphene‐based fibers are designed and prepared via synergistic toughening of ionic and covalent bonding. The tensile strength reaches up to 842.6 MPa and is superior to all ...other reported graphene‐based fibers. In addition, its electrical conductivity is as high as 292.4 S cm−1. This bioinspired synergistic toughening strategy supplies new insight toward the construction of integrated high‐performance graphene‐based fibers in the near future.
PDF
