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Fine particulate matter (PM2.5) has been manifested to be one of the major health-threatening airborne pollutants in the urban environment, as it is composed of inhalable particles, which may have considerable adverse health effects on the human respiratory system. However, there is limited evidence on the difference in these effects among various population groups in China. This paper aimed to perform a comparative analysis on the health effect of PM2.5 on hospital admissions of acute respiratory infections (ARI) for both children and adults. Total 39604 hospital admission records were collected from 98 hospitals and then matched with air pollution data from 19 monitoring stations from January 1 to December 31 in 2014. A spatial correlation test was used to estimate the spatial dependency and a time series analysis designed with a distributed lag non-linear model was further involved to evaluate the associations between PM2.5 pollution and ARI admissions. Significant effect distinctions were detected between children and adults, mainly revealing in acute lower respiratory infections (ALRI). For ALRI, the spatial correlation coefficient between population exposure and hospital admissions was 0.69 for children and 0.34 for adults. Meanwhile, for children, significant associations between PM2.5 and ALRI admissions were found at quite low concentrations (slightly above zero) and lasted for six days, with each 10-μg/m3 increase in PM2.5 corresponded to a 4.3% (95%CI: 1.2%, 7.2%) increase in the number of admissions. While for adults, no significant association emerged until the concentration of PM2.5 exceeded a threshold value (100 μg/m3 for the lag of two days) and lasted no more than three days. Our results suggested that short-term exposures to PM2.5 were associated with increased risk of ALRI admissions for children and adults in various ways, and emphasized the needs for specific preventive measures for different age groups.

PurposeMicroRNAs can influence many biological processes and have shown promise as cancer biomarkers. Few studies have focused on the expression of microRNA-223 (miR-223) and its precise role in breast cancer (BC). We aimed to examine the expression level of miR-223 and its prognostic value in BC.MethodsTissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with a locked nucleic acid (LNA) probe was used to detect miR-223 expression in 450 BC tissue samples. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using the Kaplan-Meier method and Cox regression model.ResultsOS and DFS were prolonged in the high miR-223 expression group compared to the low miR-223 expression group (p < 0.0001 and p = 0.017, respectively), especially in patients with the triple-negative breast cancer (TNBC) subtype (p = 0.046 and p < 0.001, respectively). Univariate and multivariate Cox regression analyses revealed that TNM stage (p = 0.008), the molecular subtype (p = 0.049), and miR-223 (p < 0.001) were independently associated with OS and DFS. External validation was performed with the METABRIC and The Cancer Genome Atlas (TCGA) databases via online webtools and was consistent with the data described above.ConclusionsThis study provides evidence that high miR-223 expression at diagnosis is associated with improved DFS and OS for BC patients, especially those with the TNBC subtype. miR-223 is a valid and independent prognostic biomarker in BC.

Abstract Satellite retrieved soil moisture (SM) shows great potential in hydrological, meteorological, ecological, and agricultural applications, while the coarse resolution limits its utilization in regional scale. The regression tree‐based machine learning algorithms reveal promising capability in SM downscaling. However, it lacks systematic study dedicated to intercomparisons of algorithms to explicitly illuminate their characteristics. In this study, comparisons are made to systematically evaluate performances of classification and regression tree (CART), random forest (RF), gradient boost decision tree (GBDT), and extreme gradient boost (XGB) in Soil Moisture Active Passive (SMAP) SM downscaling in southwest France. The results show that the four algorithms downscaled SM are capable of capturing spatial distribution features of the original SMAP SM. The downscaled regions with favorable accuracy are mostly situated in the dominant Mediterranean climate zone with moderate vegetation coverage and mild topography variation. The best results are obtained by GBDT in grassland with R value of 0.77 and ubRMSE value of 0.04 m3/m3. The RF and XGB also achieve good performances. On the whole, the GBDT approach is robust and reliable, which could downscale SM with superior correlation and smaller bias than the others. Besides, it achieves higher accuracy than the original SMAP in grassland and shrubland. The feature importance index of each explainable variable fluctuates regularly among different seasons and models. This study proves the outstanding performance of GBDT in SMAP SM downscaling and is expected to act as a valuable reference for studies focusing on SM scale conversion algorithms.

Age-related cataract (ARC) is a main cause of blindness for elderly people. MicroRNA hsa_miR-29c-3p (miR-29c-3p) was implicated in many biological processes in complicated diseases. However, the biological mechanism of miR-29c-3p in ARC is still undefined. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that miR-29c-3p was lowly expressed, while FBJ murine osteosarcoma viral oncogene homolog (FOS) and KCNQ1 overlapping transcript 1 (KCNQ1OT1) were highly expressed in cataract tissues and in TGF-β2-treated SRA01/04 cells. Western blot assay indicated that TGF-β2 could promote epithelial-mesenchymal transition (EMT). Moreover, our data suggested that miR-29c-3p overexpression suppressed EMT, cell proliferation and promoted apoptosis in TGF-β2-treated SRA01/04 cells. The dual-luciferase reporter assay verified that FOS was a target of miR-29c-3p and miR-29c-3p was directly targeted by KCNQ1OT1. Furthermore, KCNQ1OT1 could regulate FOS expression by sponging miR-29c-3p. Functional assays revealed that miR-29c-3p regulated FOS to repress EMT, cell proliferation and facilitate apoptosis in TGF-β2-treated SRA01/04 cells mediated by KCNQ1OT1. In conclusion, KCNQ1OT1/miR-29c-3p/FOS axis played a vital role in the progression of ARC.

Background: Increasing evidence has shown the beneficial effects of Rhodiola species on metabolic disorders, but their mechanisms are not clear. Hepatic steatosis is closely related to metabolic disorders, we aim to investigate the therapeutic effects of Rhodiola crenulata root (RCR) on fructose-induced hepatic steatosis and explore the underlying mechanisms. Purpose: To observe the effect of Rhodiola crenulata root extract (RCR) on fructose-induced hepatic steatosis in Sprague-Dawley (SD) rats and explore its possible mechanism. Methods: Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. Liver lipid deposition and morphological changes were observed by Oil red O staining. Real-time fluorescence quantitative PCR, Western blot and immunoprecipitation were used to detect gene and protein expression in liver. Results: RCR (50 mg/kg) reversed liquid fructose-induced increase in hepatic triglyceride content in rats. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in RCR-treated rats. However, RCR treatment did not affect chow intake and body weight of rats. Although some genes of the pathways involved in DNL (ChREBP, SREBP-1c, FAS, ACC1, SCD1, DGAT1, DGAT2 and MGAT2), fatty acid β-oxidation (PPARα, CPT1a, ACO and FGF21), VLDL-export (MTTP) and decomposition (HSL, ATGL) in the liver of fructose-fed rats were not changed significantly after RCR administration, the decrease in PPARα and PGC-1α proteins was reversed by RCR. Notably, SIRT1 mRNA and protein expression increased significantly with RCR administration. Furthermore, RCR increased expression of ATG4B, Beclin1 and decreased expression of Bcl2-Beclin1 complex dramatically. Meanwhile, RCR decreased the acetylation of beclin1. Moreover, RCR increased expression of autophagosome markers including LC3B and ATG5-ATG12-ATG16L1, and decreased expression of autophagolysosome marker p62 in the livers of fructose-fed rats. Conclusions: RCR has a certain improvement effect on fructose-induced hepatic steatosis, which is related to the activation of autophagy.

Abstract Freshwater stored on land is an extremely vital resource for all the terrestrial life on Earth. But our ability to record the change of land water storage is weak despite its importance. In this study, we attempt to establish a data‐driven model for simulating terrestrial water storage dynamics by relating climate forcings with terrestrial water storage anomalies (TWSAs) from the Gravity Recovery and Climate Experiment (GRACE) satellites. In the case study in Pearl River basin, China, the relationships were learned by using two ensemble learning algorithms, the Random Forest (RF) and eXtreme Gradient Boost (XGB), respectively. The TWSA in the basin was reconstructed back to past decades and compared with the TWSA derived from global land surface models. As a result, the RF and XGB algorithms both perform well and could nicely reproduce the spatial pattern and value range of GRACE observations, outperforming the land surface models. Temporal behaviors of the reconstructed TWSA time series well capture those of both GRACE and land surface models time series. A multiscale GRACE‐based drought index was proposed, and the index matches the Standardized Precipitation‐Evapotranspiration Index time series at different time scales. The case analysis for years of 1963 and 1998 indicates the ability of the reconstructed TWSA for identifying past drought and flood extremes. The importance of different input variables to the TWSA estimation model was quantified, and the precipitation of the prior 2 months is the most important variable for simulating the TWSA of the current month in the model. Results of this study highlight the great potentials for estimating terrestrial water storage dynamics from climate forcing data by using machine learning to achieve comparable results than complex physical models.

Chloride diffusion-induced corrosion is a major factor that affects the durability of concrete structures. Thus, the study of chloride diffusion in concrete is important. In this study, a mesoscopic structure model is proposed and used to investigate chloride diffusion in concrete. The concrete is assumed to be a heterogeneous material composed of two phases of aggregate and mortar matrix. The aggregates are randomly distributed convex polygons. The chloride diffusion is assumed to occur only in the mortar matrix phase. The modified chloride diffusion coefficient in the mesoscale model is proposed. The effect of a single aggregate in chloride diffusion in concrete is analyzed. The present numerical model is validated on the basis of the experimental data. The influence of aggregate in the presented model, including aggregate random distribution form, aggregate content, and the validity of polygonal aggregate based on circle, is explored further. The simulation results indicate that the polygonal aggregate random distribution has a negligible influence on chloride diffusion in concrete, the polygonal aggregate content has a certain effect, and the presented mesoscale numerical model is an effect method for predicting the chloride diffusion in concrete.

Chloride diffusion is the major factor that affects the life of concrete structures. The time-fractional order equation can be used to describe anomalous diffusion in reinforced concrete. In this work, a time-fractional model of chloride diffusion is solved via the meshless method. The Element-Free Galerkin (EFG) meshless method does not require meshing. One-dimensional and two-dimensional numerical examples are presented. Numerical results are in good agreement with theoretical solutions. The initiation time of corrosion is predicted in the presented model. Simulation results are compared with experimental data. The good agreement between EFG and experimental data indicates that time-fractional chloride diffusion in concrete can be modeled effectively by using the EFG method. This method is beneficial for further research on anomalous chloride diffusion in concrete.

The PI3K pathway is altered across various cancer types. Here the authors use amplicon exon sequencing to analyze the landscape of somatic mutations affecting the PI3K pathway specifically in breast cancer patients in China.

Abstract Background More and more cases of human infections with avian influenza A H7N9 have been reported since it was first mentioned in 2013 in China, but concurrence of influenza A H7N9 with Mycoplasma pneumoniae, however, has never been described. Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well. Case presentation Our patient was an 80-year-old Chinese woman who presented with fever, cough, chest tightness, and shortness of breath. A computed tomography scan showed obvious infiltrations at lower parts of both lungs. Arterial blood gas analysis confirmed a severe respiratory failure (type I). Her sputum and throat swabs were checked for nucleic acid of influenza A and the result was positive for influenza A H7N9. She was diagnosed as having severe influenza A H7N9 and acute respiratory distress syndrome, and was admitted to an intensive care unit. She was given comprehensive treatment, including oseltamivir, methylprednisolone, immunoglobulin, gastric protection, and noninvasive mechanical ventilation. Her condition improved 4 days later. However, some symptoms exacerbated again 2 days later with ground-glass changes appearing in upper area of right lung and the titer of antibody to Mycoplasma pneumoniae rising from 1:80 to 1:640. She was reasonably considered to be infected with Mycoplasma pneumoniae as well, and azithromycin and moxifloxacin were added to her treatment. Oseltamivir was discontinued because of three consecutive negative results of nucleic acid for influenza A H7N9, but anti-Mycoplasma treatment was continued. Although her symptoms and abnormal changes on computed tomography scan slowly went away, she finally recovered from the mixed infection after a total of 33 days of management. Conclusion In patients with confirmed influenza A H7N9 infection whose condition worsens again, especially with new infiltration or lung ground-glass infiltration, one should suspect infection by other pathogens such as Mycoplasma pneumoniae.

Abstract Bacterial communities of biofilms growing on artificial substrates were examined at two time periods (7 and 14 days) and two locations (lentic and lotic areas) in a hypereutrophic urban river of eastern China. Previous studies in this river network indicated that variations of microbial communities were the major factor affecting the distribution of antibiotic resistant genes highlighting the importance of understanding controls of microbial communities. Bacterial communities associated with biofilms were determined using epifluorescence microscopy and high-throughput sequencing. Results showed that sampling time and site had significant effects on the abundances of surface-associated bacteria. No significant differences were found in the number of surface-associated bacteria between two substrate types (filament vs. slide). Sequencing revealed microbial communities attached to artificial substrates in a hypereutrophic urban river were composed of 80,375 OTUs, and distributed in 47 phyla. Proteobacteria and Cyanobacteria/Chloroplast were the two dominant phyla, followed by Planctomycetes, Actinobacteria, Verrucomicrobia, Firmicutes and Bacteroidetes. Taxonomic composition showed ammonia-oxidizing microorganisms, fecal indicator bacteria and pathogens enriched in attached microbial communities, especially the ammonia-oxidizing Nitrosomonas bacteria. These results indicated that there were significant temporal and intra-river heterogeneity of attached microbial community structure, but no significant difference in community composition was detected between the two substrate types.

Chronic obstructive pulmonary disease (COPD) is a major and increasingly prevalent respiratory health problem worldwide and the fine particulate matter (PM2.5) is now becoming a rising health threat to it. This study aims to conduct a comparison analysis of health effect on acute exacerbation of COPD (AECOPD) associated with PM2.5 exposure in two typical cities (Beijing and Shenzhen) with different levels of PM2.5 pollution. Both correlational relationship and causal connection between PM2.5 exposure and AECOPD are investigated by adopting a time series analysis based on the generalized additive model (GAM) and convergent cross mapping (CCM). The results from GAM indicate that a 10 μg/m3 increase in PM2.5 concentration is associated with 2.43% (95% CI, 0.50–4.39%) increase in AECOPD on Lag0-2 in Beijing, compared with 6.65% (95% CI, 2.60–10.87%) on Lag0-14 in Shenzhen. The causality detection with CCM reveals similar significant causative impact of PM2.5 exposure on AECOPD in both two study areas. Findings from two methods agree that PM2.5 has non-negligible health effect on AECOPD in both two study areas, implying that air pollution can cause adverse consequences at much lower levels than common cognition. Our study highlights the adverse health effect of PM2.5 on people with COPD after exposure to different levels of PM2.5 and emphasizes that adverse effect in area with relative low pollution level cannot be overlooked. Governments in both high-pollution and low-pollution cities should attach importance to the adverse effects of PM2.5 on humans and take corresponding measures to control and reduce the related losses.

Near field communication (NFC) is a kind of short-range wireless communication technology which has been applied around the world.The applications of mobile payments and access control are the most common applications of NFC technology.Technically,the NFC device can be used as a bank card or an entrance card with the help of the card emulation mode of NFC,which will be validated by external reader.It is very essential to select a appropriate and safe certification scheme in this scenario.First of all,the existing NFC authentication system and security scheme was introduced and the system security requirements and potential security risks were analyzed.Then,by using Hash,AES and password Key dynamic updating mechanism,a mutual authentication security scheme for mobile NFC devices was proposed,and the synchronization mechanism was designd.Finally,GNY logic was used to prove the security correctness of our proposed scheme.The security analysis shows that our scheme can avoid a number of attacks,such as forgery,replay attack,eavesdropping,tampering attack,asynchronous attack and so on.

Stromal cell–derived factor 1 (SDF-1) and its receptor CXCR4 have shown to play a role in embryonic development process, regulation of hematopoiesis, mediating immunology response, inflammatory reaction, and metastasis of malignant tumor. Recently, SDF-1 and CXCR4 are also closely related to retinal neovascularization. This study was to investigate the expression of SDF-1 and CXCR4 in the retina after optic nerve injury in pregnant rats so as to reveal its significance. A total of 12 pregnant rats were randomly divided into normal group and experimental group (after 5 days of optic nerve injury), six rats in each group; expressions of SDF-1 as well as CXCR4 in rat retina were detected by immunofluorescence staining and western blot assay. The result of immunofluorescence staining showed that the relative gray scale values of SDF-1 and CXCR4 in the experimental group were significantly higher than those in the normal group ( P

Crop residue burning is the major biomass burning activity in China, strongly influencing the regional air quality and climate. As the cultivation pattern in China is rather scattered and intricate, it is a challenge to derive an accurate emission inventory for crop residue burning. In this study, we proposed a remote sensing-based method to estimate nitrogen oxide (NOx) emissions related to crop residue burning at the field level over Hubei, China. The new method considers differences in emission factors and the spatial distribution for different crop types. Fire radiative power (FRP) derived from moderate-resolution imaging spectroradiometer (MODIS) was used to quantify NOx emissions related to agricultural biomass combustion. The spatial distribution of different crops classified by multisource remote sensing data was used as an a priori constraint. We derived a new NOx emission database for Hubei from 2014 to 2016 with spatial resolution of 1 × 1 km. Significant seasonal patterns were observed from the NOx emission database. Peak NOx emission occurring in October was related to the residue burning in late autumn harvesting. Another peak was observed between January and April, which was due to the frequent burning of stubble before spring sowing. Our results were validated by comparing our emission inventory with geostationary satellite observations, previous studies, global fire emission database (GFED), NO2 vertical column densities (VCDs) from ozone monitoring instrument (OMI) satellite observations, and measurements from environmental monitoring stations. The comparisons showed NOx emission from GFED database was 47% lower than ours, while the evaluations from most of the statistical studies were significantly higher than our results. The discrepancies were likely related to the differences of methodology and data sources. The spatiotemporal variations of NOx emission in this study showed strong correlations with NO2 VCDs, which agreed well with geostationary satellite observations. A reasonable correlation between in situ NO2 observations and our results in agricultural regions demonstrated that our method is reliable. We believe that the new NOx emission database for crop residue burning derived in this study can potentially improve the understanding of pollution sources and can provide additional information for the design of pollution control measures.

Land surface temperature (LST) is a key parameter in geophysical fields. The Moderate Resolution Imaging Spectroradiometer (MODIS) onboard Terra provides an accurate LST dataset with global coverage and monthly series, but the monthly MODIS LST data are often obscured by clouds and other atmospheric disturbances and consequently exhibit significant data gaps at a global scale, resulting in a difficult interpretation of LST trends and climatological characteristics. In this paper, an effective and fast LST reconstruction method to fill data gaps in monthly MODIS LST is presented. The proposal combines the Discrete Cosine Transform (DCT) and the Penalized Least Square approach (PLS) together with the Generalized Cross-Validation (GCV) criterion. It depends only on the spatial high-frequency information from original LST estimates and allows a fast and automatic filling process without the help of any other ancillary data. To analyze its performance, the method is applied to fill data gaps on three continents with synthetic random missing values introduced as validation sets. The statistical evaluation shows that this method is capable of filling a large number of missing values in MODIS LST datasets with very high accuracy. In addition, the trend differences between the original LST and reconstructed LST have assessed the significance by computing 95% confidence intervals for a time series of trend differences is examined. Simulated experiments show that data gaps with large missing counts lead to significant differences in trend patterns and the patterns on validation sets are well estimated by this method, which confirms that the filling process of MODIS LST is necessary and favorable results can be produced for substantial data gaps by the DCT-PLS method.

Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.

Incarvillea compacta Maxim is a traditional Tibetan plant widely used to treat rheumatic pain and bruises. We conducted qualitative analyses by liquid chromatography-mass spectrometry and quantitative analyses of the total phenols, flavonoids, and alkaloids content of different extracts of I. compacta Maxim. Antioxidant and analgesic activity were analyzed. The results showed that the methanol extract had the highest content of the various ingredients. A total of 25 constituents were identified, of which compounds 1−23 were found for the first time in this plant. The water extract had the highest capacity to clear free radicals in the antioxidant test. The water extract had dose-dependent analgesic effects in the first and second phase in a formalin test. The latency of pain from a hot-plate test was augmented by the water extract when the dose was greater than or equal to 30 g/kg. The water extract significantly decreased the amount of writhing in a dose-dependent manner compared with the control group in the acetic acid-induced writhing test. These results showed that I. compacta Maxim is a new antioxidant and analgesic agent, and this study provides information on its ingredients for further study.

Hawk tea is a rich and edible resource, traditionally used as a beverage in South China. This drink has many pharmacologic effects, such as acting as an antioxidant and reducing blood sugar and lipids. The objective of this work was to explore the active compound contents, bioactivities and their monthly changes, and optimize the harvest time. In the present study, Hawk tea from each month in 2017 was collected and extracted with 70% (v/v) ethanol. The contents of the total flavonoids and total phenols were determined using the colorimetric method. We determined the contents of seven characteristic active substances—hyperin, isoquercitrin, trifolin, quercitrin, astragalin, quercetin, and kaempferol—using high-performance liquid chromatography. The crude extract was tested for its antioxidant and inhibitory properties on enzymes involved in metabolic syndrome. Specifically, 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing power assay, and the inhibition capacity test on α-glucosidase and lipase were conducted to determine the antioxidant effect in vitro, as well as the reduction of blood sugar and lipids. Monthly variations in activities and components were determined by numeric analysis and comparison. Correlation analysis revealed that antioxidant effects are significantly correlated with the total flavonoids. The hierarchical cluster analysis of bioactivities and their contents indicates that October and November are the best harvesting months, which differs with the habitual collection of Hawk tea.

Background: Advanced oxidation protein products (AOPPs), a marker of oxidative stress, are prevalent in many kinds of disorders. Rheumatoid arthritis (RA), mainly resulting from the dysfunction of fibroblast-like synoviocytes (FLSs), is related to oxidative stress. Although the increased levels of AOPPs in RA patients were reported, the effect of AOPPs on FLSs function still remains unclear. Therefore, our study aims to investigate whether AOPPs have an effect on the inflammatory response of FLSs in vitro. Methods: FLSs obtained from both knees of rats were treated with or without AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. The mRNA and protein expression of tumor necrosis factor (TNF)-a, interleukin(IL)-1ß, matrix metalloproteinases(MMP)-3, MMP-13 and vascular endothelial growth factor (VEGF) were measured by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Reactive oxygen species (ROS) generation was detected by fluorescent microscope and fluorescence microplate reader. Immunoprecipitation, Co-Immunoprecipitation and western blot were performed to examine the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and nuclear factor kappa B (NF-κB). Results: Exposure of FLSs to AOPPs upregulated the mRNA and protein expression of TNF-a, IL-1ß, MMP-3, MMP-13 and VEGF in a concentration dependent manner. AOPPs treatment triggered ROS production in FLSs, which was significantly abolished by ROS scavenger N-acetyl-L-cysteine (NAC), superoxide dismutase (SOD), NADPH oxidase inhibitors diphenyleneiodonium (DPI) and apocynin. Challenged AOPPs induced phosphorylation of p47phox, triggered an interaction between p47phox, p22phox and gp91phox, and significantly upregulated expression of NADPH oxidase subunits p47phox, p22phox and gp91phox. IκB degradation and nuclear translocation of NF-κB p65 induced by AOPPs were significantly blocked by SOD, NAC, DPI and apocynin. Conclusions: These data indicate that AOPPs induce inflammatory response in FLSs is medicated through NADPH oxidase-dependent activation of NF-κB.

This paper presents a comparison of CO2 products derived from Scanning Imaging Absorption Spectrometer for Atmospheric Cartography (SCIAMACHY), Greenhouse Gases Observing Satellite (GOSAT) and Atmospheric Infrared Sounder (AIRS), with reference to calibration data obtained using the high-resolution ground-based Fourier Transform Spectrometers (g-b FTS) in the Total Carbon Column Observing Network (TCCON). Based on the monthly averages, we calculate the global offsets and regional relative precisions between satellite products and g-b FTS measurements. The results are as follows: the monthly means of SCIAMACHY data are systemically slightly lower than g-b FTS, but limited in coverage; the GOSAT data are superior in stability, but inferior in systematic error; the mean difference between AIRS data and that of g-b FTS is small; and the monthly global coverage is above 95%. Therefore, the AIRS data are better than the other two satellite products in both coverage and accuracy. We also estimate linear trends based on monthly mean data and find that the differences between the satellite products and the g-b FTS data range from 0.25 ppm (SCIAMACHY) to 1.26 ppm (AIRS). The latitudinal distributions of the zonal means of the three satellite products show similar spatial features. The seasonal cycle of satellite products also illustrates the same trend with g-b FTS observations.

Degradation of RC structures due to chloride penetration followed by reinforcement corrosion is a serious problem in civil engineering. The numerical simulation methods at present mainly involve finite element methods (FEM), which are based on mesh generation. In this study, element-free Galerkin (EFG) and meshless weighted least squares (MWLS) methods are used to solve the problem of simulation of chloride diffusion in concrete. The range of a scaling parameter is presented using numerical examples based on meshless methods. One- and two-dimensional numerical examples validated the effectiveness and accuracy of the two meshless methods by comparing results obtained by MWLS with results computed by EFG and FEM and results calculated by an analytical method. A good agreement is obtained among MWLS and EFG numerical simulations and the experimental data obtained from an existing marine concrete structure. These results indicate that MWLS and EFG are reliable meshless methods that can be used for the prediction of chloride ingress in concrete structures.

Nucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer.Two sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software.There were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.956-8.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.160-0.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001).Our study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC.

Monitoring the dynamic characteristics of the diffuse attenuation coefficient (Kd(490)) on the basis of the high temporal-resolution satellite data is critical for regulating the ecological environment of lake. By measuring the in-situ Kd(490) and the remote-sensing reflectance, a semi-analytical algorithm for Kd(490) was developed to determine the short-term variation of Kd(490). From 2006 to 2014, the data about 412 samples (among which 60 were used as match-up points, 282 for calibrating dataset and the remaining 70 for validating dataset) were gathered from nine expeditions to calibrate and validate the aforesaid semi-analytical algorithm. The root mean square percentage error (RMSP) and the mean absolute relative error (MAPE) of validation datasets were respectively 27.44% and 22.60 ± 15.57%, while that of the match-up datasets were respectively 34.29% and 27.57 ± 20.56%. These percentages indicate that the semi-analytical algorithm and Geostationary Ocean Color Imager (GOCI) data are applicable to obtain the short-term variation of Kd(490) in the turbid shallow inland waters. The short-term GOCI-observed Kd(490) shows a significant seasonal and spatial variation and a similar distribution to the matching Moderate Resolution Imaging Spectroradiometer (MODIS) which derived Kd(490). A comparative analysis on wind (observed by buoys) and GOCI-derived Kd(490) suggests that wind is a primary driving factor of Kd(490) variation, but the lacustrine morphometry affects the wind force that is contributing to Kd(490) variation.

With the rapid pace of urban expansion, comprehensively understanding urban spatial patterns, built environments, green-spaces distributions, demographic distributions, and economic activities becomes more meaningful. Night Time Lights (NTL) images acquired through the Operational Linescan System of the US Defense Meteorological Satellite Program (DMSP/OLS NTL) have long been utilized to monitor urban areas and their expansion characteristics since this system detects variation in NTL emissions. However, the pixel saturation phenomenon leads to a serious limitation in mapping luminance variations in urban zones with nighttime illumination levels that approach or exceed the pixel saturation limits of OLS sensors. Consequently, we propose an NTL-based city index that utilizes the Moderate-resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST) and Enhanced Vegetation Index (EVI) images to regulate and compensate for desaturation on NTL images acquired from corresponding urban areas. The regulated results achieve good performance in differentiating central business districts (CBDs), airports, and urban green spaces. Consequently, these derived imageries could effectively convey the structural details of urban cores. In addition, compared with the Vegetation Adjusted NTL Urban Index (VANUI), LST-and-EVI-regulated-NTL-city index (LERNCI) reveals superior capability in delineating the spatial structures of selected metropolis areas across the world, especially in the large cities of developing countries. The currently available results indicate that LERNCI corresponds better to city spatial patterns. Moreover, LERNCI displays a remarkably better “goodness-of-fit” correspondence with both the Version 1 Nighttime Visible Infrared Imaging Radiometer Suite Day/Night Band Composite (NPP/VIIRS DNB) data and the WorldPop population-density data compared with the VANUI imageries. Thus, LERNCI can act as a helpful indicator for differentiating and classifying regional economic activities, population aggregations, and energy-consumption and city-expansion patterns. LERNCI can also serve as a valuable auxiliary reference for decision-making processes that concern subjects such as urban planning and easing the central functions of metropolis.

Mounting evidence suggests that the FAK N-terminal (FERM) domain controls FAK phosphorylation and function; however, little is known regarding the role of the C terminal (FAT) domain in FAK regulation. We identified a patient-derived FAK mutant, in which a 27-amino acid segment was deleted from the C-terminal FAT domain (named FAK-Del33). When FAK-Del33 was overexpressed in specific tumor cell lines, Y397 phosphorylation increased compared with that observed in cells expressing FAK-WT. Here, we attempt to unveil the mechanism of this increased phosphorylation. Using cell biology experiments, we show that FAK-Del33 is incapable of co-localizing with paxillin, and has constitutively high Y397 phosphorylation. With a kinase-dead mutation, it showed phosphorylation of FAK-Del33 has enhanced through auto-phosphorylation. It was also demonstrated that phosphorylation of FAK-Del33 is not Src dependent or enhanced intermolecular interactions, and that the hyperphosphorylation can be lowered using increasing amounts of transfected FERM domain. This result suggests that Del33 mutation disrupting of FAT's structural integrity and paxillin binding capacity leads to incapable of targeting Focal adhesions, but has gained the capacity for auto-phosphorylation in cis.

The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry. Significantly higher median percentages of circulating MDL-1-expressing monocytes were observed in active RA patients (53.6%) compared to inactive RA patients (34.1%), OA patients (27.9%), and HC (21.2%). Levels of MDL-1 and DAP12 gene expression in PBMCs and their protein expression in the synovium were significantly higher in active RA patients than in inactive RA or OA patients. MDL-1 levels were positively correlated with parameters of disease activity, articular damage, and levels of proinflammatory cytokines. MDL-1 activator (Dengue virus type 2 antigen) stimulation on PBMCs resulted in significantly enhanced levels of proinflammatory cytokines in RA patients compared to those in OA patients or HC, indicating that MDL-1 activation is functional. Frequencies of MDL-1-expressing monocytes and levels of MDL-1 and DAP12 gene expression significantly decreased after effective therapy. Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in RA patients, suggesting their roles in regulating articular inflammation.

Spatially varying haze is a common feature of most satellite images currently used for land cover classification and mapping and can significantly affect image quality. In this paper, we present a high-fidelity haze removal method based on Haze Optimized Transformation (HOT), comprising of three steps: semi-automatic HOT transform, HOT perfection and percentile based dark object subtraction (DOS). Since digital numbers (DNs) of band red and blue are highly correlated in clear sky, the R-squared criterion is utilized to search the relative clearest regions of the whole scene automatically. After HOT transform, spurious HOT responses are first masked out and filled by means of four-direction scan and dynamic interpolation, and then homomorphic filter is performed to compensate for loss of HOT of masked-out regions with large areas. To avoid patches and halo artifacts, a procedure called percentile DOS is implemented to eliminate the influence of haze. Scenes including various land cover types are selected to validate the proposed method, and a comparison analysis with HOT and Background Suppressed Haze Thickness Index (BSHTI) is performed. Three quality assessment indicators are selected to evaluate the haze removed effect on image quality from different perspective and band profiles are utilized to analyze the spectral consistency. Experiment results verify the effectiveness of the proposed method for haze removal and the superiority of it in preserving the natural color of object itself, enhancing local contrast, and maintaining structural information of original image.

BACKGROUND: Resistance to chemotherapy is the major cause of failure in breast cancer treatment. Recent studies suggest that secreted proteins may play important roles in chemoresistance. We sought to systematically characterize secreted proteins associated with drug resistance, which may represent potential serum biomarkers or novel drug targets. METHODOLOGY/PRINCIPAL FINDINGS: In the present work, we adopted the proteomic strategy of one-dimensional gel electrophoresis followed by liquid chromatography-tandem mass spectrometry to compare the secretome of MCF-7 and doxorubicin-resistant MCF-7/Dox. A total of 2,084 proteins were identified with at least two unique peptides in the conditioned media of two cell lines. By quantification with label-free spectral counting, 89 differentially expressed secreted proteins (DESPs) between the two cell lines were found. Among them, 57 DESPs were first found to be related to doxorubicin resistance in this work, including 24 extracellular matrix related proteins, 2 cytokines and 31 unclassified proteins. We focused on 13 novel DESPs with confirmed roles in tumor metastasis. Among them, the elevated expression of IL-18 in doxorubicin-resistant cell lines and breast tumor tissues was validated and its role in doxorubicin resistance was further confirmed by cell viability experiments in the presence or absence of this protein. CONCLUSIONS/SIGNIFICANCE: Comparative analysis of the secretome of MCF-7 and MCF-7/Dox identified novel secreted proteins related to chemotherapy resistance. IL-18 was further validated to contribute to doxorubicin resistance, in addition to its confirmed role in breast cancer metastasis. Due to its dual roles in both drug resistance and tumor metastasis, IL-18 may represent a useful drug target for breast cancer therapy.