Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivities, and the inhibitory effects of several flavonoids against EV71 have been studied in cell cultures; however, to date, there are no reported data on their effects in animal models. In this study, we confirmed the in vitro activities of eight flavonoids against EV71 infection, based on the inhibition of cytopathic effects. Moreover, these flavonoids were found to reduce viral genomic RNA replication and protein synthesis. We further demonstrated the protective efficacy of these flavonoids in newborn mice challenged with a lethal dose of EV71. Apigenin, luteolin, kaempferol, formononetin, and penduletin conferred survival protection of 88.89%, 91.67%, 88.89%, 75%, and 66.67%, respectively, from the lethal EV71 challenge. In addition, isorhamnetin provided the highest mice survival protection of 100% at a dose of 10 mg/kg. This study, to the best of our knowledge, is the first to evaluate the in vivo anti-EV7l activities of multiple flavonoids, and we accordingly identified flavonoids as potential leading compounds for anti-EV71 drug development.
BackgroundHuman enterovirus type 71 (EV71) and Coxsackievirus A group type 16 (CA16) belong to human Enterovirus species A of the family Picornaviridae. These viruses are recognized as the major pathogens responsible for epidemics of hand-foot-mouth disease (HFMD), which presents with fever and vesicular eruptions of palms, soles of the feet or mouth. Human scavenger receptor class B, member 2 (SCARB2) has been identified as the receptor for both EV71 and CA16, as overexpression of SCARB2 in cells can enhance virus replication significantly.MethodsIn this study, we used a lentivirus packaging vector to transduce the SCARB2 gene into human embryonic kidney cells (293), human rhabdomyosarcoma cells (RD) and African green monkey kidney cells (Vero) to create stable expression lines. Expression of SCARB2 in the resulting three transgenic cell lines was confirmed by real-time RT-PCR, immunofluorescence and flow cytometry.ResultsLevels of SCARB2 mRNA determined by real-time RT-PCR in 293-SCARB2 (293S) or RD-SCARB2 (RDS) transgenic cell lines were approximately 2 × 102 times higher than those in 293 and RD cells, respectively, and three times higher in Vero-SCARB2 (VeroS) than in Vero cells. Furthermore, EV71 and CA16 virus titers in 293S and RDS cells were 102–103-fold higher (detected in RD cell) than those in the parental cells, and a 10-fold higher titer of EV71 was achieved in VeroS cells compared with that in Vero cells.ConclusionsWe established for the first time three cell lines stably overexpressing SCARB2, which showed drastic increases in susceptibility to EV71/CA16 infection. These optimal cell lines may be utilized to develop inactivated vaccines for EV71/CA16 and facilitate rapid detection and isolation of HFMD pathogens or other Enterovirus serotypes. Furthermore, these stable cell lines also can serve as tools to facilitate drug screenings as well as molecular studies on virus-host interactions and pathogenesis of causative agents for HFMD.
By far the theories of consumer knowledge are mainly estimated in the western countries. It is important and necessary to assess theory generalizability and model equivalence across different culture contexts. This paper intends to gain a preliminary understanding of the relationship between two consumer knowledge components and four product‐related task performances, with a focus on the influences of two psycho‐linguistic differences in cognition. Based on the results of our empirically multi‐group comparison of Chinese and French wine consumers, we find that consumer knowledge is a multidimensional construct in both cultural contexts. It appears that psycho‐linguistic differences largely affect the consumption task performance. Consequently different consumer knowledge components play different roles in consumption tasks and lead wine consumers to employ dissimilar information processing strategies in various cultural contexts.
In recent years, a type of cyberattacks, known as advanced persistent threats, has resulted in very serious losses to various organizations such as governments and enterprises. The APT has the characteristics of long duration, complex attack means, and strong ability to conceal themselves, which make it difficult to detect them. Due to the lack of proper means to protect the Information-centric IoT (ICIoT), the ICIoT devices are extremely vulnerable to APT attacks. Moreover, among the existing APT detection methods, most researchers adopt those that extract the features of different APT attacks, and most of the features extracted are local, which leads to the fact that the related methods have poor scalability, thus reducing the accuracy. Furthermore, the attackers can easily avoid the detection by changing the local features. In this paper, we find that it is inevitable that the infected host will generate C&C communication with the command and control server (C&C server), during the process of APT attacks, and the C&C domain names are the bridge connecting the internal infection with the C&C server. Moreover, a certain APT attack of one attack family, which is the assembly of the same APT attacks, tends to map the C&C domain names to the same IP subnet. Under the assumption that the APT attackers have limited attack resources, the relationship between C&C domain names of APT and IP subnet is inevitable for the APT attackers to get higher attack efficiency, which leads to the effective tracking of APT attack behavior. Therefore, we construct a detection method based on the domain names' graph structure. This detection method can improve the detection efficiency in the information-centric internet, especially for the IoT devices. And, at the same time, we employ an appropriate pruning strategy and a preprocessing method to reduce the size of data to be processed and improve the computational efficiency. This detection method can also reduce the detection range, increase the detection accuracy, and improve the robustness and scalability of the detection system. In the actual experiment, the data size we process is 257535071 DNS requests and 73136 domain names. The experiment shows that the C&C domain names can be effectively detected even with a small-scale seed domain names. INDEX TERMS APT, malicious domain, graph, ICIoT, C&C server.
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