Increasing epidemiological studies have shown that a rapid temperature change within 1 day is an independent risk factor for human health. This paper aimed to systematically review the epidemiological evidence on the relationship between diurnal temperature range (DTR) and human health and to propose future research directions. A literature search was conducted in October 2013 using the databases including PubMed, ScienceDirect, and EBSCO. Empirical studies regarding the relationship between DTR and mortality and morbidity were included. Twenty-five relevant studies were identified, among which, 11 investigated the relationship between DTR and mortality and 14 examined the impact of DTR on morbidity. The majority of existing studies reported that DTR was significantly associated with mortality and morbidity, particularly for cardiovascular and respiratory diseases. Notably, compared with adults, the elderly and children were more vulnerable to DTR effects. However, there were some inconsistencies regarding the susceptible groups, lag time, and threshold of DTR. The impact of DTR on human health may be confounded or modified by season, socioeconomic, and educational status. Further research is needed to further confirm the adverse effects of DTR in different geographical locations; examine the effects of DTR on the health of children aged one or under; explore extreme DTR effects on human health; analyze the difference of DTR effects on human health in different locations and the modified effects of potential confounding factors; and develop detailed preventive measures against large DTR, particularly for susceptible groups.

Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses. Our near-atomic resolution structure of CVA6 A-particle complexed with a neutralizing antibody maps an immune-dominant neutralizing epitope to the surface loops of VP1. The structure-guided cell-based inhibition studies further demonstrate that these loops could serve as excellent targets for designing anti-CVA6 vaccines.

Highlights d Atomic models show CVA16 can simultaneously bind three distinct potent nAbs d The neutralization sites vary across three forms of CVA16 d CVA16 mature virion bearing conserved epitopes is the optimal vaccine immunogen d nAb-based assay allows quantification of mature virions for vaccine development

Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.

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Hand, foot and mouth disease (HFMD) is a serious public health problem that has emerged over the past several decades. Pathogen detection by the Chinese national HFMD surveillance system has focused mainly on enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Therefore, epidemiological information regarding the other causative enteroviruses is limited. To identify the pandemic enterovirus in Suzhou, Jiangsu province, China, clinical samples from patients with HFMD were collected from 2012 to 2013 and analyzed. The results revealed that CA16 was the most dominant HFMD pathogen in 2012, whereas CA6 and CA10 were the dominant pathogens in 2013. Phylogenetic analysis revealed that the C4a sub-genogroup of EV71 and the B1a and B1b sub-genogroups of CA16 continued to evolve and circulate in Suzhou. The CA6 strains were assigned to six genotypes (A–F) and the CA10 strains were assigned to seven genotypes (A–G), with clear geographical and temporal distributions. All of the CA6 strains in Suzhou belonged to genogroup F, and there were several lineages circulating in Suzhou. All of the CA10 strains in Suzhou belonged to genogroup G, and they had the same genetic origin. Co-infections of EV71/CA16 and CA6/CA10 were found in the samples, and bootscan analysis of 5′-untranslated regions (UTRs) revealed that some CA16 strains in Suzhou had genetic recombination with EV71. This property might allow CA16 to alter its evolvability and circulating ability. This study underscores the need for surveillance of CA6 and CA10 in the Yangtze River Delta and East China.

Temperature increase between neighboring days has a significant adverse impact on mortality. Further health mitigation strategies as a response to climate change should take into account temperature variation between neighboring days.

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