Human enterovirus 71 uncoating captured at atomic resolution.

UNLABELLED: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children, and structural characterization of EV71 during its life cycle can aid in the development of therapeutics against HFMD. Here, we present the atomic structures of the full virion and an uncoating intermediate of a clinical EV71 C4 strain to illustrate the structural changes in the full virion that lead to the formation of the uncoating intermediate prepared for RNA release. Although the VP1 N-terminal regions observed to penetrate through the junction channel at the quasi-3-fold axis in the uncoating intermediate of coxsackievirus A16 were not observed in the EV71 uncoating intermediate, drastic conformational changes occur in this region, as has been observed in all capsid proteins. Additionally, the RNA genome interacts with the N-terminal extensions of VP1 and residues 32 to 36 of VP3, both of which are situated at the bottom of the junction. These observations highlight the importance of the junction for genome release. Furthermore, EV71 uncoating is associated with apparent rearrangements and expansion around the 2- and 5-fold axes without obvious changes around the 3-fold axes. Therefore, these structures enabled the identification of hot spots for capsid rearrangements, which led to the hypothesis that the protomer interface near the junction and the 2-fold axis permits the opening of large channels for the exit of polypeptides and viral RNA, which is an uncoating mechanism that is likely conserved in enteroviruses. IMPORTANCE: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children. EV71 contains an RNA genome protected by an icosahedral capsid shell. Uncoating is essential in EV71 life cycle, which is characterized by conformational changes in the capsid to facilitate RNA release into host cell. Here we present the atomic structures of the full virion and an uncoating intermediate of a clinical C4 strain of EV71. Structural analysis revealed drastic conformational changes associated with uncoating in all the capsid proteins near the junction at the quasi-3-fold axis and protein-RNA interactions at the bottom of the junction in the uncoating intermediate. Significant capsid rearrangements also occur at the icosahedral 2- and 5-fold axes but not at the 3-fold axis. Taking the results together, we hypothesize that the junction and nearby areas are hot spots for capsid breaches for the exit of polypeptides and viral RNA during uncoating.

A massive mandibular keloid with severe infection: What is your treatment?

A case report of massive mandibular keloid with severe infection induced by acne achieved resolution of skin lesions after combined treatment with surgery and high concentration single-dose 5-aminolevulinic acid photodynamic therapy (5-ALA PDT). The patient achieved satisfactory effects, after receiving combined treatment with radiotherapy, secondary healing, intralesional injection of glucocorticoids, and other treatments. The scar didn't exhibit growth in a follow-up check after a year. This case provides evidence that photodynamic therapy is effective in the treatment of massive mandibular keloid with severe infection.

[Prevalence and influencing factors of deciduous caries in preschool children in Chongqing city].

OBJECTIVE: This study aimed to determine the prevalence and related factors of deciduous caries in 3-5-year-old preschool children in Chongqing city. Results will be used to provide a basis for the establishment and adjustment of prevention and intervention of caries in preschool children. METHODS: We referred to the Fourth National Oral Health Epidemiological Survey. Data included caries prevalence in preschool children, and the questionnaires were distributed to children' parents in Chongqing city. Results were inputted by Epidata 3.1 and statistically analyzed using SPSS 21.0. RESULTS: A total of 1 350 preschool children were included in the study. We found that maxillary deciduous central incisor and mandibular deciduous molars were susceptible to decay. The prevalence of primary teeth caries in preschool children in Chongqing city was 51.4% (694/1 350). The mean decayed-missing-filled-teeth (dmft) index was 2.34. The caries prevalence and mean dmft between age groups were statistically significant (P<0.01) and increased with age (P<0.05). However, except the 5-year-old group (P<0.05), no significant difference in caries prevalence rate and mean dmft was found between male and female children (P>0.05). Approximately 61.7% of caries cases were concentrated in a small number (36.1%) of individuals. Multivariate Logistic regression analysis showed that age, highest educational level of parents, intake frequency of sweetened beverages and carbonated drinks, toothache or similar discomfort experience over the past year, dentist visits, and parents' assessment of teeth and oral health status of children were the factors influencing the prevalence of deciduous caries (P<0.05). CONCLUSIONS: More than half of the preschool children had dental caries. Majority of caries were concentrated in a small number of individuals. The age of children, highest educational level of parents, intake frequency of sweetened beverages and carbonated drinks, toothache or discomfort experience over the past year, dentist visits, and parents' assessment of teeth and oral health status of children were associated with the prevalence of deciduous caries.

[An investigation on the need, the utilization, and the influencing factors of dental services for pre-school children in selected areas in Chongqing province].

OBJECTIVE: The aim of this study is to survey the need, the utilization, and the influencing factors of dental services for children in selected areas in Chongqing province by investigating their oral health status. The survey will provide references for preventive oral health care in targeted Chongqing areas, which may improve the level of oral health among pre-school children. METHODS: Random cluster sampling was utilized according to standards of the Fourth National Oral Health Epidemiological sampling survey, and 1 300 children between the ages of three and four years old from 24 kindergartens in 12 subdistricts of three areas in Chongqing were interviewed for free dental checkups and to participate in the survey. The questionnaires were designed according to the Anderson model and were answered by the children's parents. The results were analyzed utilizing Chi-square test logistic regression. RESULTS: The prevalence rate of caries among the pre-school children in selected areas of Chongqing was 55.4%, the decay, missing, filled surface (dmfs) was 6 696, the mean dmfs was 5.2, and the caries filling constituent ratio was 2.3%. A total of 1 173 questionnaires were analyzed. The ratio for seeing a dentist for therapeutic reasons was 6.31% (74/1 173) and for prevalence was 22.93% (269/1 173). CONCLUSIONS: The oral health service needs of pre-school children in selected areas of Chongqing are large and the oral health service utilization rate is low. Oral health care processes are arduous; thus, targeted oral prevention policies should be created.

Unusual Fe(CN)6³â»/4⁻ capture induced by synergic effect of electropolymeric cationic surfactant and graphene: characterization and biosensing application.

Herein, a special microheterogeneous system for Fe(CN)6(3-/4-) capture was constructed based on graphene (GN) and the electropolymeric cationic surfactant, an amphiphilic pyrrole derivative, (11-pyrrolyl-1-yl-undecyl) triethylammonium tetrafluoroborate (A2). The morphology of the system was characterized by scanning electron microscope. The redox properties of the entrapped Fe(CN)6(3-/4-) were investigated by cyclic voltammetry and UV-visible spectrometry. The entrapped Fe(CN)6(3-/4-) exhibited highly electroactive with stable and symmetrical cyclic voltammetric signal. A dramatic negative shift in the half wave potential can be obtained due to the unusual Fe(CN)6(3-/4-) partitioning in in this microheterogeneous system based on poly(A2+GN). Finally, the entrapped Fe(CN)6(3-/4-) was applied in the construction of the enhanced biosensors to hydrogen peroxide and sulfide.

Global transcriptomic analysis of human neuroblastoma cells in response to enterovirus type 71 infection.

Human enterovirus type 71 (EV71) is the major pathogen of hand-foot-and-mouth disease (HFMD) and has been associated with severe neurological disease and even death in infants and young children. The pathogenesis of EV71 infection in the human central nervous system remains unclear. In this study, human whole genome microarray was employed to perform transcriptome profiling in SH-SY5Y human neuroblastoma cells infected with EV71. The results indicated that EV71 infection lead to altered expression of 161 human mRNAs, including 74 up-regulated genes and 87 down-regulated genes. Bioinformatics analysis indicated the possible roles of the differentially regulated mRNAs in selected pathways, including cell cycle/proliferation, apoptosis, and cytokine/chemokine responses. Finally, the microarray results were validated using real-time RT-PCR with high identity. Overall, our results provided fundamental information regarding the host response to EV71 infection in human neuroblastoma cells, and this finding will help explain the pathogenesis of EV71 infection and virus-host interaction.

Sequence analysis of six enterovirus 71 strains with different virulences in humans.

Enterovirus 71 (EV71) infection is the main cause of hand, foot and mouth disease (HFMD) and has been associated with severe neurological diseases resulting in high mortalities. In this study, six EV71 strains isolated from patients with different clinical symptoms were sequenced and analyzed in a mouse model of EV71 infection. In a phylogenetic tree, based on the complete VP1 gene sequence, all six strains grouped into the C4 genotype. The sequence analysis revealed that there are nucleotide changes clustered in the internal ribosome entry site (IRES) element of the 5'-nontranslated region (5'-NTR), as well as amino acid differences clustered in the non-structural proteins. Importantly, we identified a unique amino acid difference (Val(1994)-Ile(1994)) that distinguished the more virulent strains, Anhui1 (Ah1), Henan1 (Hn1) and Henan2 (Hn2) from the less virulent strains, Chongqing1 (Cq1), Chongqing2 (Cq2) and Chongqing3 (Cq3). This amino acid difference is located in the finger domain of the viral RNA-dependent RNA polymerase 3D (3D(pol)). Furthermore, two-day-old Balb/c mice were inoculated with the Ah1, Hn1, Hn2, Cq1, Cq2 and Cq3 isolates by the intracerebral or intraperitoneal routes. All of the mice inoculated with Ah1, Hn1 and Hn2 isolates developed hind-leg paralysis and subsequently died. Mice inoculated with the Cq1, Cq2 or Cq3 isolates survived throughout the 21-day observation period. These results show that clinical isolates of EV71 associated with disease of different severity in humans have characteristic sequence differences and cause different mortality rates when inoculated into mice. These data also provide a rational basis to investigate the molecular determinants of EV71 pathogenesis using a reverse genetic approach.