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Background: Understanding geospatial impacts of multi-sourced influencing factors on the epidemic of hand-foot-and-mouth disease (HFMD) is of great significance for formulating disease control policies tailored to regional-specific needs, yet the knowledge is very limited. We aim to identify and further quantify the spatiotemporal heterogeneous effects of environmental and socioeconomic factors on HFMD dynamics. Methods: We collected monthly province-level HFMD incidence and related environmental and socioeconomic data in China during 2009–2018. Hierarchical Bayesian models were constructed to investigate the spatiotemporal relationships between regional HFMD and various covariates: linear and nonlinear effects for environmental covariates, and linear effects for socioeconomic covariates. Results: The spatiotemporal distribution of HFMD cases was highly heterogeneous, indicated by the Lorenz curves and the corresponding Gini indices. The peak time (R2 = 0.65, P = 0.009), annual amplitude (R2 = 0.94, P<0.001), and semi-annual periodicity contribution (R2 = 0.88, P<0.001) displayed marked latitudinal gradients in Central China region. The most likely cluster areas for HFMD were located in south China (Guangdong, Guangxi, Hunan, Hainan) from April 2013 to October 2017. The Bayesian models achieved the best predictive performance (R2 = 0.87, P<0.001). We found significant nonlinear associations between monthly average temperature, relative humidity, normalized difference vegetation index and HFMD transmission. Besides, population density (RR = 1.261; 95%CI, 1.169–1.353), birth rate (RR = 1.058; 95%CI, 1.025–1.090), real GDP per capita (RR = 1.163; 95%CI, 1.033–1.310) and school vacation (RR = 0.507; 95%CI, 0.459–0.559) were identified to have positive or negative effects on HFMD respectively. Our model could successfully predict months with HFMD outbreaks versus non-outbreaks in provinces of China from Jan 2009 to Dec 2018. Conclusions: Our study highlights the importance of refined spatial and temporal data, as well as environmental and socioeconomic information, on HFMD transmission dynamics. The spatiotemporal analysis framework may provide insights into adjusting regional interventions to local conditions and temporal variations in broader natural and social sciences. Author summary: Hand-foot-and-mouth disease (HFMD) is one of the most common pediatric infectious diseases worldwide and it has affected up to two million children annually in China since 2008. This study used Bayesian spatiotemporal modeling to analyze provincial-level HFMD cases, environmental and socioeconomic data during 2009–2018. We found that both environmental (temperature, relative humidity and normalized difference vegetation index) and socioeconomic covariates (population density, birth rate, real GDP per capita and school vacation) are associated with HFMD occurrence under spatiotemporal scales. This model may help to (1) identify outbreaks of HFMD, including their timing, location and severity; (2) understand the transmission dynamics by mapping the spread of HFMD over time and space; (3) indicate areas of higher risk or the emergence of new outbreaks by detecting clusters of HFMD cases in specific geographic locations. Overall, this study provides valuable information for public health decision-makers and researchers, allowing them to better understand the spread of the disease and target their efforts more efficiently to control its transmission and prevent outbreaks. [ABSTRACT FROM AUTHOR]

Because synonymy treatment traditionally relies on morphological judgments, it usually causes many problems in species delimitation and in the biodiversity catalogue. For example, Diplopterygium simulans, which belongs to the Gleicheniaceae family, has been considered to be synonymous with D. glaucum or D. giganteum based mainly on the morphology of its pinna rachis and blade. In the absence of molecular evidence, these revisions remain doubtful. DNA barcoding, which is considered to be a powerful method for species-level identification, was employed to assess the genetic distance among 9 members of the Diplopterygium genus. The results indicate that D. simulans is an independent species rather than a synonymy of D. glaucum or D. giganteum. Moreover, phylogenetic analysis uncovered the sisterhood of D. simulans and D. cantonense, which is supported by their geographical distributions and morphological traits. Incorrect synonymy treatment is prevalent in the characterization of biological diversity, and our study proposes a convenient and effective method for validating synonym treatments and discovering cryptic species. [ABSTRACT FROM AUTHOR]

Background: Ectopic angiogenesis within the intima and media is considered to be a hallmark of advanced vulnerable atherosclerotic lesions. Some studies have shown that specific matrix metalloproteinases (MMPs) might play different roles in angiogenesis. Therefore, we investigated the predominant effects of specific MMPs in intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. Methods and Results: New Zealand rabbits underwent balloon injury of the abdominal artery and ingestion of a high-cholesterol (1%) diet to establish an atherosclerotic animal model. At weeks 4, 6, 8, 10, and 12 after balloon injury, five rabbits were euthanized and the abdominal aorta was harvested. Blood lipid analysis, intravascular ultrasound imaging, pathologic and immunohistochemical expression studies, and western blotting were performed. From weeks 4 to 12, the expression of MMP-1, -2, -3, and -9 and vascular endothelial growth factor A (VEGF-A) increased with atherosclerotic plaque development in the abdominal aorta, while the expression of MMP-14 substantially decreased. The vulnerability index (VI) gradually increased over time. Intraplaque neovessels appeared at week 8. The microvessel density (MVD) was greater at week 12 than at week 8. The VI, MVD, and VEGF-A level were positively correlated with the MMP-1, -2,-3, and -9 levels within plaques. Negative correlations were noted between the MMP-14 level and the VI, MVD, and VEGF-A level. Conclusion: Upregulation of MMP-1, -2, -3, and -9 and downregulation of MMP-14 may contribute to intraplaque angiogenesis and plaque instability at the advanced stage of atherosclerosis in rabbits. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial DNA polymerase gamma (POLG1) mutations were associated with levodopa-responsive Parkinsonism. POLG1 gene contains a number of common nonsynonymous SNPs and intronic regulatory SNPs which may have functional consequences. It is of great interest to discover polymorphisms variants associated with Parkinson's disease (PD), both in isolation and in combination with specific SNPs., Materials and Methods: We conducted a case-control study and genotyped twenty SNPs and poly-Q polymorphisms of POLG1 gene including in 344 Chinese sporadic PD patients and 154 healthy controls. All the polymorphisms of POLG1 we found in this study were sequenced by PCR products with dye terminator methods using an ABI-3100 sequencer. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) for association between twenty POLG1 SNPs and PD were calculated using the program Haploview., Principal Results: We provided evidence for strong association of four intronic SNPs of the POLG1 gene (new report: c.2070-12T>A and rs2307439: c.2070-64G>A in intron 11, P = 0.00011, OR = 1.727; rs2302084: c.3105-11T>C and rs2246900: c.3105-36A>G in intron 19, P = 0.00031, OR = 1.648) with PD. However, we did not identify any significant association between ten exonic SNPs of POLG1 and PD. Linkage disequilibrium analysis indicated that c.2070-12T>A and c.2070-64G>A could be parsed into one block as Haplotype 1 as well as c.3105-11T>C and c.3105-36A>G in Haplotype 2. In addition, case and control study on association of POLG1 CAG repeat (poly-Q) alleles with PD showed a significant association (P = 0.03, OR = 2.16) of the non-10/11Q variants with PD. Although intronic SNPs associated with PD didn't influence POLG1 mRNA alternative splicing, there was a strong association of c.2070-12T>A and c.2070-64G>A with decreased POLG1 mRNA level and protein levels., Conclusions: Our findings indicate that POLG1 may play a role in the pathogenesis of PD in Chinese populations.