h i g h l i g h t sWe propose a novel hybrid model to forecast PM 2.5 pollution.Using trajectory based geographic parameter as an extra input to ANN model. Applying prediction strategy at different scales and then sum them up. The model is capable to predict the high peaks of PM 2.5 concentrations. a b s t r a c tIn the paper a novel hybrid model combining air mass trajectory analysis and wavelet transformation to improve the artificial neural network (ANN) forecast accuracy of daily average concentrations of PM 2.5 two days in advance is presented. The model was developed from 13 different air pollution monitoring stations in Beijing, Tianjin, and Hebei province (Jing-Jin-Ji area). The air mass trajectory was used to recognize distinct corridors for transport of "dirty" air and "clean" air to selected stations. With each corridor, a triangular station net was constructed based on air mass trajectories and the distances between neighboring sites. Wind speed and direction were also considered as parameters in calculating this trajectory based air pollution indicator value. Moreover, the original time series of PM 2.5 concentration was decomposed by wavelet transformation into a few sub-series with lower variability. The prediction strategy applied to each of them and then summed up the individual prediction results. Daily meteorological forecast variables as well as the respective pollutant predictors were used as input to a multi-layer perceptron (MLP) type of back-propagation neural network. The experimental verification of the proposed model was conducted over a period of more than one year (between September 2013 and October 2014). It is found that the trajectory based geographic model and wavelet transformation can be effective tools to improve the PM 2.5 forecasting accuracy. The root mean squared error (RMSE) of the hybrid model can be reduced, on the average, by up to 40 percent. Particularly, the high PM 2.5 days are almost anticipated by using wavelet decomposition and the detection rate (DR) for a given alert threshold of hybrid model can reach 90% on average. This approach shows the potential to be applied in other countries' air quality forecasting systems.

The presence and characterization of plasmid-mediated fosfomycin resistance determinants among Escherichia coli isolates collected from pets in China between 2006 and 2010 were investigated. Twenty-nine isolates (9.0%) were positive for fosA3, and all of them were CTX-M producers. The fosA3 genes were flanked by IS26 and were localized on F2:A؊:B؊ plasmids or on very similar F33:A؊:B؊ plasmids carrying both bla CTX-M-65 and rmtB. These findings indicate that the fosA3 gene may be coselected by antimicrobials other than fosfomycin.

The purpose of this study was to examine the occurrence of fosfomycin-resistant Escherichia coli from chickens and to characterize the plasmids carrying fosA3. A total of 661 E. coli isolates of chicken origin collected from 2009 to 2011 were screened for plasmid-mediated fosfomycin resistance determinants by PCR. Plasmids were characterized using PCR-based replicon typing, plasmid multilocus sequence typing, and restriction fragment length polymorphisms. Associated addiction systems and resistance genes were identified by PCR. PCR-mapping was used for analysis of the genetic context of fosA3. Fosfomycin resistance was detected in 58 isolates that also carried the fosA3 gene. Fifty-seven, 17, and 52 FosA3-producers also harbored blaCTX−M, rmtB, and floR genes, respectively. Most of the 58 fosA3-carrying isolates were clonally unrelated, and all fosA3 genes were located on plasmids belonged to F33:A-:B- (n = 18), IncN-F33:A-:B- (n = 7), IncHI2/ST3 (n = 10), IncI1/ST71 (n = 3), IncI1/ST108 (n = 3), and others. The genetic structures, IS26-ISEcp1-blaCTX−M−55-orf477-blaTEM-1-IS26-fosA3-1758bp-IS26 and ISEcp1-blaCTX−M−65-IS903-iroN-IS26-fosA3-536bp-IS26 were located on highly similar F33:A-:B- plasmids. In addition, blaCTX−M−14-fosA3-IS26 was frequently present on similar IncHI2/ST3 plasmids. IncFII plasmids had a significantly higher frequency of addiction systems (mean 3.5) than other plasmids. Our results showed a surprisingly high prevalence of fosA3 gene in E. coli isolates recovered from chicken in China. The spread of fosA3 can be attributed to horizontal dissemination of several epidemic plasmids, especially F33:A-:B- plasmids. Since coselection by other antimicrobials is the major driving force for the diffusion of the fosA3 gene, a strict antibiotic use policy is urgently needed in China.

pHN7A8 is a chimera that may have resulted from the acquisition, by recombination in the plasmid backbone, of the multiresistance region found in pXZ. This region appears to have evolved from the resistance determinant R100 through the stepwise integration of multiple antimicrobial resistance determinants from different sources by the actions of mobile elements and recombination. The successful dissemination of this multidrug resistance plasmid presents further challenges for the prevention and treatment of Enterobacteriaceae infections.

The members of the Snail superfamily of zinc-finger transcription factors, including Snai1 and Snai2, are involved in essential biological processes, such as epithelial-mesenchymal transition (EMT). While Snai1 has been investigated in a number of cancers, our knowledge on Snai2 and its role(s) in squamous cell carcinoma of oral tongue (SCCOT) is limited. In this study, we confirmed the previous observation that over-expression of Snai2 is a frequent event in SCCOT. We further demonstrated that Snai2 over-expression is associated with lymph node metastasis in two independent SCCOT patient cohorts (total n = 129). Statistical analysis revealed that Snai2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of Snai2 was correlated with reduced E-cadherin expression and enhanced Vimentin expression, suggesting a functional role of Snai2 in EMT. These observations were confirmed in vitro, in which knockdown of Snai2 induced a switch from a mesenchymal-like morphology to an epithelial-like morphology in SCCOT cell lines, and suppressed the cell invasion and migration. In contrast, ectopic transfection of Snai2 led to enhanced cell invasion and migration. Furthermore, Snai2 knockdown attenuated TGFβ1-induced EMT in SCCOT cell lines. Taken together, these data suggest that Snai2 plays major roles in EMT and the progression of SCCOT, and may serve as a therapeutic target for patients at risk of metastasis.

BackgroundWe previously demonstrated that 25-hydroxyvitamin D3 concentrations in gingival crevicular fluid are 300 times higher than those in the plasma of patients with aggressive periodontitis. Here we explored whether 25-hydroxyvitamin D3 can be synthesized by periodontal soft tissue cells. We also investigated which of the two main kinds of hydroxylases, CYP27A1 and CYP2R1, is the key 25-hydroxylase in periodontal soft tissue cells.Methodology/Principal FindingsPrimary cultures of human gingival fibroblasts and periodontal ligament cells from 5 individual donors were established. CYP27A1 mRNA, CYP2R1 mRNA and CYP27A1 protein were detected in human gingival fibroblasts and periodontal ligament cells, whereas CYP2R1 protein was not. After incubation with the 25-hydroxylase substrate vitamin D3, human gingival fibroblasts and periodontal ligament cells generated detectable 25-hydroxyvitamin D3 that resulted in the production of 1α,25-dihydroxyvitamin D3. Specific knockdown of CYP27A1 in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 production. Knockdown of CYP2R1 did not significantly influence 25-hydroxyvitamin D3 synthesis. Sodium butyrate did not influence significantly CYP27A1 mRNA expression; however, interleukin-1β and Porphyromonas gingivalis lipopolysaccharide strongly induced CYP27A1 mRNA expression in human gingival fibroblasts and periodontal ligament cells.ConclusionsThe activity of 25-hydroxylase was verified in human gingival fibroblasts and periodontal ligament cells, and CYP27A1 was identified as the key 25-hydroxylase in these cells.

Compared with traditional dental training methods, virtual reality training systems integrated with multisensory feedback possess potentials advantages. However, there exist many technical challenges in developing a satisfactory simulator. In this manuscript, we systematically survey several current dental training systems to identify the gaps between the capabilities of these systems and the clinical training requirements. After briefly summarising the components, functions and unique features of each system, we discuss the technical challenges behind these systems including the software, hardware and user evaluation methods. Finally, the clinical requirements of an ideal dental training system are proposed. Future research/development areas are identified based on an analysis of the gaps between current systems and clinical training requirements.

BackgroundWe previously demonstrated that 25-hydroxyvitamin D3, the precursor of 1α,25-dihydroxyvitamin D3, is abundant around periodontal soft tissues. Here we investigate whether 25-hydroxyvitamin D3 is converted to 1α,25-dihydroxyvitamin D3 in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1α,25-dihydroxyvitamin D3 in periodontal soft tissue cells.Methodology/Principal FindingsWe established primary cultures of human gingival fibroblasts and human periodontal ligament cells from 5 individual donors. We demonstrated that 1α-hydroxylase was expressed in human gingival fibroblasts and periodontal ligament cells, as was cubilin. After incubation with the 1α-hydroxylase substrate 25-hydroxyvitamin D3, human gingival fibroblasts and periodontal ligament cells generated detectable 1α,25-dihydroxyvitamin D3 that resulted in an up-regulation of CYP24A1 and RANKL mRNA. A specific knockdown of 1α-hydroxylase in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 1α,25-dihydroxyvitamin D3 production and mRNA expression of CYP24A1 and RANKL. The classical renal regulators of 1α-hydroxylase (parathyroid hormone, calcium and 1α,25-dihydroxyvitamin D3) and Porphyromonas gingivalis lipopolysaccharide did not influence 1α-hydroxylase expression significantly, however, interleukin-1β and sodium butyrate strongly induced 1α-hydroxylase expression in human gingival fibroblasts and periodontal ligament cells.Conclusions/SignificanceIn this study, the expression, activity and functionality of 1α-hydroxylase were detected in human gingival fibroblasts and periodontal ligament cells, raising the possibility that vitamin D acts in an autocrine/paracrine manner in these cells.