Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease.

Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

Exploring Multiple Application Scenarios of Visual Communication Course Using Deep Learning Under the Digital Twins.

The emergence of intelligent technology has brought a particular impact and allows for virtuality-reality interaction in the educational field. In particular, digital twins (DTs) feature virtuality-reality symbiosis, solid virtual simulation, and high real-time interaction. It has also seen extended applications to the field of education. This study optimizes the design of the visual communication (Viscom) course based on the deep learning (DL) algorithm. Firstly, the theory of DL is analyzed following the relevant literature, and the typical DL networks, network structures, and related algorithms are introduced. Secondly, Viscom technology is expounded, and DL technology is applied to the Viscom course. Then, the applicability and feasibility of DL in the Viscom course are analyzed through a questionnaire survey (QS) design by collecting students' attitudes towards Viscom courses before and after the experiment. After introducing DL into the Viscom course, the results show that students' learning interest and satisfaction with the practical knowledge mastery have increased. However, the satisfaction with theoretical knowledge mastery before practical courses has decreased; overall, the teaching effect of the Viscom course has been improved. Therefore, the introduction of DL into the DT-enabled Viscom can provide a reference for developing the Viscom course. The research content offers technical support (TS) for integrating DT technology and modern education.