Stable C and N isotopes of PM2.5 and size-segregated particles emitted from incense stick and cigarette burning.

This work measured the δ13C and δ15N signatures in PM2.5 and size-segregated particles emitted from incense stick and cigarette burning in different brands or nicotine contents for pollution source identification indoors. Three popular brands of incense stick and cigarette were selected for experiments. A personal environmental monitoring sampler and a Sioutas cascade impactor were used to collect PM2.5 and size-segregated particles, respectively, for isotopic signatures analyses. Our data showed that both δ13C and δ15N values were heavier from incense stick burning (δ13C: 27.3 ± 0.5; δ15N: 8.63 ± 1.35) than cigarette (δ13C: 28.5 ± 0.2; δ15N: 4.15 ± 0.69). The scatter plots of δ13C and TC/PM2.5 and of δ15N and TN/PM2.5 can be applied to distinguish particle pollution sources and assess the influence of cigarette burning to PM2.5 according to different nicotine contents. The δ13C values in size-segregated particles were similar to incense stick or cigarette burning; the δ13C values in PM2.5 were significantly higher than those in size-segregated particles. However, the nitrogen amount was too low in most of the size-segregated particles to analyze δ15N from incense stick and cigarette burning. These results suggest that the δ13C signatures on PM2.5 cannot represent the isotopic characteristics of size-segregated particles and δ15N has limitation for pollution source identification of different particle sizes.

Estimations of infiltration factors of diurnal PM2.5 and heavy metals in children's bedrooms.

Children are the sensitive population to fine particulate matter (PM2.5 ) exposure and spend most of their time in bedroom. Infiltration factor (Finf ) can be used to calculate the fraction of total indoor PM2.5 with outdoor origin to increase the accuracy of exposure assessment. However, studies have ignored the diurnal variations of PM2.5 Finf values, and a few studies have estimated Finf values for heavy metals in PM2.5 in children's bedrooms. To calculate the PM2.5 Finf , real-time indoor and outdoor PM2.5 concentrations and occupants' activities were collected in 56 study bedrooms. At 22 of the 56 study bedrooms, PM2.5 samples were also collected for heavy metals analysis. We noted the PM2.5 Finf was higher during the daytime (0.70 ± 0.23) than nighttime (0.54 ± 0.27) during the hot season, and the time of air conditioner use was longer at nighttime. The largest Finf value of heavy metal was V (0.88 ± 0.25), followed by Pb (0.85 ± 0.28), Mn (0.72 ± 0.26), Cr (0.69 ± 0.35), and Zn (0.61 ± 0.32), with a larger variation. Our findings suggest that the estimations of diurnal PM2.5 and heavy metals Finf values are necessary to increase the accuracy of exposure assessment.

A novel mouse model of sporadic colon cancer induced by combination of conditional Apc genes and chemical carcinogen in the absence of Cre recombinase.

Although valuable insights into colon cancer biology have been garnered from human colon cancer cell lines and primary colonic tissues, and animal studies using human colon cancer xenografts, immunocompetent mouse models of spontaneous or chemically induced colon cancer better phenocopy human disease. As most sporadic human colon tumors present adenomatous polyposis coli (APC) gene mutations, considerable effort has gone into developing mice that express mutant Apc alleles that mimic human colon cancer pathogenesis. A serious limitation of many of these Apc-mutant murine models, however, is that these mice develop numerous tumors in the small intestine but few, if any, in the colon. In this work, we examined three spontaneous mouse models of colon tumorigenesis based upon the widely used multiple intestinal neoplasia (Min) mouse: mice with either constitutive or conditional Apc mutations alone or in combination with caudal-related homeobox transcription factor CDX2P-Cre transgene - either with or without exposure to the potent colon carcinogen azoxymethane. Using the CDX2 promoter to drive Cre recombinase transgene expression effectively inactivated Apc in colonocytes, creating a model with earlier tumor onset and increased tumor incidence/burden, but without the Min mouse model's small intestine tumorigenesis and susceptibility to intestinal perforation/ulceration/hemorrhage. Most significantly, azoxymethane-treated mice with conditional Apc expression, but absent the Cre recombinase gene, demonstrated nearly 50% tumor incidence with two or more large colon tumors per mouse of human-like histology, but no small intestine tumors - unlike the azoxymethane-resistant C57BL/6J-background Min mouse model. As such this model provides a robust platform for chemoprevention studies.

Intensifying the Antimicrobial Activity of Poly[2-( tert-butylamino)ethyl Methacrylate]/Polylactide Composites by Tailoring Their Chemical and Physical Structures.

Poly[2-( tert-butylaminoethyl) methacrylate] (PTA), an important class of antimicrobial polymers, has demonstrated its great biocidal efficiency, favorable nontoxicity, and versatile applicability. To further enhance its antimicrobial efficiency, an optimization of the chemical structure of PTA polymers is performed via atom transfer radical polymerization (ATRP) in terms of the antimicrobial ability against Escherichia coli ( E. coli) and Staphylococcus aureus ( S. aureus). After the optimization, the resulting PTA is blended into a polylactide (PLA) matrix to form PTA/PLA composite thin films. It is first found, that the antimicrobial efficiency of PTA/PLA composites was significantly enhanced by controlling the PLA crystallinity and the PLA spherulite size. A possible mechanistic route regarding this new finding has been rationally discussed. Lastly, the cytotoxicity and mechanical properties of a PTA/PLA composite thin film exhibiting the best biocidal effect are evaluated for assessing its potential as a new material for creating antimicrobial biomedical devices.

Seeing Better and Going Deeper in Cancer Nanotheranostics.

Biomedical imaging modalities in clinical practice have revolutionized oncology for several decades. State-of-the-art biomedical techniques allow visualizing both normal physiological and pathological architectures of the human body. The use of nanoparticles (NP) as contrast agents enabled visualization of refined contrast images with superior resolution, which assists clinicians in more accurate diagnoses and in planning appropriate therapy. These desirable features are due to the ability of NPs to carry high payloads (contrast agents or drugs), increased in vivo half-life, and disease-specific accumulation. We review the various NP-based interventions for treatments of deep-seated tumors, involving "seeing better" to precisely visualize early diagnosis and "going deeper" to activate selective therapeutics in situ.

Microwave-Synthesized Platinum-Embedded Mesoporous Silica Nanoparticles as Dual-Modality Contrast Agents: Computed Tomography and Optical Imaging.

Nanoparticle-based imaging contrast agents have drawn tremendous attention especially in multi-modality imaging. In this study, we developed mesoporous silica nanoparticles (MSNs) for use as dual-modality contrast agents for computed tomography (CT) and near-infrared (NIR) optical imaging (OI). A microwave synthesis for preparing naked platinum nanoparticles (nPtNPs) on MSNs (MSNs-Pt) was developed and characterized with physicochemical analysis and imaging systems. The high density of nPtNPs on the surface of the MSNs could greatly enhance the CT contrast. Inductively coupled plasma mass spectrometry (ICP-MS) revealed the MSNs-Pt compositions to be ~14% Pt by weight and TEM revealed an average particle diameter of ~50 nm and covered with ~3 nm diameter nPtNPs. To enhance the OI contrast, the NIR fluorescent dye Dy800 was conjugated to the MSNs-Pt nanochannels. The fluorescence spectra of MSNs-Pt-Dy800 were very similar to unconjugated Dy800. The CT imaging demonstrated that even modest degrees of Pt labeling could result in substantial X-ray attenuation. In vivo imaging of breast tumor-bearing mice treated with PEGylated MSNs-Pt-Dy800 (PEG-MSNs-Pt-Dy800) showed significantly improved contrasts in both fluorescence and CT imaging and the signal intensity within the tumor retained for 24 h post-injection.

Enantiomeric Recognition and Separation by Chiral Nanoparticles.

Chiral molecules are stereoselective with regard to specific biological functions. Enantiomers differ considerably in their physiological reactions with the human body. Safeguarding the quality and safety of drugs requires an efficient analytical platform by which to selectively probe chiral compounds to ensure the extraction of single enantiomers. Asymmetric synthesis is a mature approach to the production of single enantiomers; however, it is poorly suited to mass production and allows for only specific enantioselective reactions. Furthermore, it is too expensive and time-consuming for the evaluation of therapeutic drugs in the early stages of development. These limitations have prompted the development of surface-modified nanoparticles using amino acids, chiral organic ligands, or functional groups as chiral selectors applicable to a racemic mixture of chiral molecules. The fact that these combinations can be optimized in terms of sensitivity, specificity, and enantioselectivity makes them ideal for enantiomeric recognition and separation. In chiral resolution, molecules bond selectively to particle surfaces according to homochiral interactions, whereupon an enantiopure compound is extracted from the solution through a simple filtration process. In this review article, we discuss the fabrication of chiral nanoparticles and look at the ways their distinctive surface properties have been adopted in enantiomeric recognition and separation.

Lectin-functionalized mesoporous silica nanoparticles for endoscopic detection of premalignant colonic lesions.

Colorectal cancer (CRC) is one of the leading causes of cancer-deaths worldwide. Methods for the early in situ detection of colorectal adenomatous polyps and their precursors - prior to their malignancy transformation into CRC - are urgently needed. Unfortunately at present, the primary diagnostic method, colonoscopy, can only detect polyps and carcinomas by shape/morphology; with sessile polyps more likely to go unnoticed than polypoid lesions. Here we describe our development of polyp-targeting, fluorescently-labeled mesoporous silica nanoparticles (MSNs) that serve as targeted endoscopic contrast agents for the early detection of colorectal polyps and cancer. In vitro cell studies, ex vivo histopathological analysis, and in vivo colonoscopy and endoscopy of murine colorectal cancer models, demonstrate significant binding specificity of our nanoconstructs to pathological lesions via targeting aberrant α-L-fucose expression. Our findings strongly suggest that lectin-functionalized fluorescent MSNs could serve as a promising endoscopic contrast agent for in situ diagnostic imaging of premalignant colonic lesions.

The transcriptional repression activity of STAF65γ is facilitated by promoter tethering and nuclear import of class IIa histone deacetylases.

Aberrant expression levels of transcriptional regulators result in alterations in transcriptional control. STAF65γ is a structural subunit of the GCN5 transcriptional co-activator complex. Reports showed that STAF65γ is highly expressed in several human cancer cells, but the consequences of this aberrant expression pattern remain elusive. Here, we show that the STAF65γ protein is highly expressed in lung adenocarcinoma patients and high levels of STAF65γ correlate with poor prognosis. High levels of STAF65γ cause repression of the c-Myc oncogene through physical association with transcription factor YY1 and co-repressors HDACs. Physical interactions between STAF65γ and class IIa HDACs facilitate nuclear enrichment and regulate the assembly of HDAC complexes. Moreover, SUMOylation of STAF65γ is necessary for maintaining the co-repressor complex containing YY1 and class IIa HDACs at the promoter. Our findings reveal a distinct role of STAF65γ in nuclear import, transcriptional repression, and cell cycle regulation at high levels of expression, which is associated with poor clinical outcomes of lung adenocarcinoma.

Illuminating and Radiosensitizing Tumors with 2DG-Bound Gold-Based Nanomedicine for Targeted CT Imaging and Therapy.

Although radiotherapy is one of the most important curative treatments for cancer, its clinical application is associated with undesired therapeutic effects on normal or healthy tissues. The use of targeted agents that can simultaneously achieve therapeutic and imaging functions could constitute a potential solution. Herein, we developed 2-deoxy-d-glucose (2DG)-labeled poly(ethylene glycol) (PEG) gold nanodots (2DG-PEG-AuD) as a tumor-targeted computed tomography (CT) contrast agent and radiosensitizer. The key advantages of the design are its biocompatibility and targeted AuD with excellent sensitivity in tumor detection via avid glucose metabolism. As a consequence, CT imaging with enhanced sensitivity and remarkable radiotherapeutic efficacy could be attained. Our synthesized AuD displayed linear enhancement of CT contrast as a function of its concentration. In addition, 2DG-PEG-AuD successfully demonstrated significant augmentation of CT contrast in both in vitro cell studies and in vivo tumor-bearing mouse models. In tumor-bearing mice, 2DG-PEG-AuD showed excellent radiosensitizing functions after intravenous injection. Results from this work indicate that 2DG-PEG-AuD could greatly potentiate theranostic capabilities by providing high-resolution anatomical and functional images in a single CT scan and therapeutic capability.

Airborne fungi and bacteria in child daycare centers and the effectiveness of weak acid hypochlorous water on controlling microbes.

A three-week-long biological sampling scheme was conducted in two child daycare centers (CDCCs) in order to investigate interdiurnal and diurnal variations in indoor airborne microbes as well as the efficiency of weak acid hypochlorous water (WAHW) on disinfecting indoor microbes. During the second week of sampling, WAHW was sprayed using a fogger in the classroom after children had left and before they returned the next morning. An identical cycle of experiments was performed twice in the winter and spring. Without WAHW intervention, the respective mean of the indoor concentrations and I/O ratios were 8732-47581 CFU m(-3) and 0.96-2.53 for fungi, and 6706-28998 CFU m(-3) and 1.10-11.92 for bacteria, showing severe bio-contamination in the CDCCs. Moreover, a relatively high level of bacterial pollution was found at noon, whereas a greater fungal pollution could be detected in the morning and at noon. Among five school days, the fungal and bacterial pollution may be higher on Monday and on Wednesday, Thursday, and Friday, respectively. Furthermore, with WAHW intervention, the indoor microbial concentrations and I/O ratios were decreased significantly. The reduction of I/O ratios caused by WAHW disinfection was accomplished in the morning for bacteria and in the morning, at noon, and in the afternoon for fungi. In conclusion, this study clearly clarified the risky period during which children may be exposed to hazardous environments, and demonstrated the effectiveness of spraying WAHW the night before on decontaminating indoor airborne microbes on the following day, especially in the case of fungi.

Recent advances in nanoparticle-based Förster resonance energy transfer for biosensing, molecular imaging and drug release profiling.

Förster resonance energy transfer (FRET) may be regarded as a "smart" technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of "visible" and "activatable" FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery.

The impact of heavy precipitation and its impact modifiers on shigellosis occurrence during typhoon season in Taiwan: A case-crossover design.

Because of climate change, heavy precipitation is likely to become frequent and intense, thereby increasing the risk of shigellosis occurrence. However, few studies examined the impact of heavy precipitation on shigellosis and its impact modifiers in developed countries. This study aims to analyze the association between heavy precipitation and shigellosis in Taiwan, and to identify the vulnerable population and impact modifiers. We adopted a case-crossover design, and used conditional logistic regression to estimate odds ratios (ORs) for shigellosis occurrence. Information were collected on the daily shigellosis cases, precipitation, temperature, and typhoons from 1994 to 2015, and yearly data of medical resources and environmental factors were obtained at the city level from 1998 to 2015. Stratification analyses were performed by age, sex, medical resource, and environmental factors. We discovered that heavy precipitation ≥80 mm/day considerably increased the risk of shigellosis occurrence. The ORs of heavy rain (80 to <200 mm/day) were 2.08-2.26 at lags 0-1. The ORs of extremely heavy rain (≥200 mm/day) increased to 2.17-4.73 at lags 5-8. Moreover, the effect of heavy precipitation was greater under high temperature condition (≥23.6 °C). Adults were more susceptible to heavy-precipitation-associated shigellosis, especially the elderly. Males experienced marginally higher effects than females did. Moreover, cities with more medical resources and forest cover and higher percentage of completed storm sewers had lower effects; however, dense population and higher pig density were the risk factors. Although the high water-supply penetration rate did not decrease Shigella infection after heavy precipitation, it did lower the risk of typhoon-related shigellosis. In conclusion, hot temperature could enhance the impact of heavy precipitation on shigellosis. Public health interventions should be introduced according to the lag period after heavy precipitation, particularly in areas with high population density, proportion of elderly people, and pig density. The improvement of medical resources and tree cover as well as the construction of storm sewers and piped water systems might be mitigation measures that can be considered.

Impact of mold growth on di(2-ethylhexyl) phthalate emission from moist wallpaper.

Flood damage can increase indoor concentrations of di(2-ethylhexyl) phthalate (DEHP) and molds in households with wallpaper. Wallpaper water content can affect its DEHP emission into indoor environments; however, the influence of mold growth on this DEHP emission remains unclear. Here, we evaluated whether mold growth affects DEHP emission from moist wallpaper (moist WP). Experiments were conducted in glass chambers with wallpaper containing 12.7% (w/w) DEHP and a dust tray sample system at approximately 28 °C and 100% relative humidity (RH). The experimental groups were (1) moist WP, (2) moist WP + Aspergillus versicolor (AV), (3) moist WP + Cladosporium cladosporioides, (4) moist WP + Penicillium chrysogenum, and (5) moist WP + mold mixture. Mold growth on the wallpaper and DEHP emission into air and onto dust were analyzed at nine time-points over 30 days. Initially, the moist WP group emitted relatively high concentrations of DEHP into air, but after at least 8 days, the concentration of DEHP emitted by the mold-added groups exceeded that of the moist WP group. DEHP emission onto dust, especially from the moist WP group, increased considerably at day 15. During the experimental period, the moist WP (13.63 ± 4.67 µg) and moist WP + AV (13.93 ± 0.49 µg) groups emitted higher cumulative amounts of DEHP onto dust. During the 30-day experimental period, obvious mold growth occurred over days 15-30. Moreover, the moist WP group exhibited relatively higher and lower cumulative DEHP emission into air than the mold-added groups during days 2-10 (2.71 vs. 1.94-2.94 µg) and 15-30 (1.16 vs. 1.61-2.12), respectively; a contrasting trend was observed for cumulative DEHP emission onto dust. In conclusion, mold growth affects DEHP emission from water-damaged wallpaper, and the removal or cleaning of wet wallpaper, particularly those with visible mold growth, is critical from a public health perspective.

Multimodal Magnetic Resonance and Photoacoustic Imaging of Tumor-Specific Enzyme-Responsive Hybrid Nanoparticles for Oxygen Modulation.

Multimodal imaging contrast agents for cancer that can not only perform diagnostic functions but also serve as tumor microenvironment-responsive biomaterials are encouraging. In this study, we report the design and fabrication of a novel enzyme-responsive T1 magnetic resonance imaging (MRI) contrast agent that can modulate oxygen in the tumor microenvironment via the catalytic conversion of H2O2 to O2. The T1 contrast agent is a core-shell nanoparticle that consists of manganese oxide and hyaluronic acid (HA)-conjugated mesoporous silica nanoparticle (HA-MnO@MSN). The salient features of the nanoparticle developed in this study are as follows: 1) HA serves as a targeting ligand for CD44-expressing cancer cells; 2) HA allows controlled access of water molecules to the MnO core via the digestion of enzyme hyaluronidase; 3) the generation of O2 bubbles in the tumor by consuming H2O2; and 4) the capability to increase the oxygen tension in the tumor. The r 1 relaxivity of HA-MnO@MSN was measured to be 1.29 mM-1s-1 at a magnetic field strength of 9.4 T. In vitro results demonstrated the ability of continuous oxygen evolution by HA-MnO@MSN. After intratumoral administration of HA-MnO@MSN to an HCT116 xenograft mouse model, T1 weighted MRI contrast was observed after 5 h postinjection and retained up to 48 h. In addition, in vivo photoacoustic imaging of HA-MnO@MSN demonstrated an increase in the tumor oxygen saturation over time after i. t. administration. Thus, the core-shell nanoparticles developed in this study could be helpful in tumor-targeted T1 MR imaging and oxygen modulation.

Ambient viral and bacterial distribution during long-range transport in Northern Taiwan.

Long-range transport (LRT) reportedly carries air pollutants and microorganisms to downwind areas. LRT can be of various types, such as dust storm (DS) and frontal pollution (FP); however, studies comparing their effects on bioaerosols are lacking. This study evaluated the effect of LRT on viral and bacterial concentrations in Northern Taiwan. When LRT occurred and possibly affected Taiwan from August 2013 to April 2014, air samples (before, during, and after LRT) were collected in Cape Fugui (CF, Taiwan's northernmost point) and National Taiwan University (NTU). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was applied to quantify influenza A virus. qPCR and qPCR coupled with propidium monoazide were, respectively, used to quantify total and viable bacteria. Types and occurrence of LRT were confirmed according to the changing patterns of meteorological factors and air pollution, air mass sources (HYSPLIT model), and satellite images. Two Asian DS and three FP cases were included in this study. Influenza A virus was detected only on days before and during FP occurred on January 3-5, 2014, with concentrations of 0.87 and 10.19 copies/m3, respectively. For bacteria, the increase in concentrations of total and viable cells during Asian DSs (17-19 and 25-29 November 2013) was found at CF only (from 3.13 to 3.40 and from 2.62 to 2.85 log copies/m3, respectively). However, bacterial levels at NTU and CF both increased during FP and lasted for 2 days after FP. In conclusion, LRT increased the levels of influenza A virus and bacteria in the ambient air of Northern Taiwan, particularly at CF. During and 2 days (at least) after LRT, people should avoid outdoor activities, especially in case of FP.

Influence of Indoor Temperature Exposure on Emergency Department Visits Due to Infectious and Non-Infectious Respiratory Diseases for Older People.

Previous studies have demonstrated that outdoor temperature exposure was an important risk factor for respiratory diseases. However, no study investigates the effect of indoor temperature exposure on respiratory diseases and further assesses cumulative effect. The objective of this study is to study the cumulative effect of indoor temperature exposure on emergency department visits due to infectious (IRD) and non-infectious (NIRD) respiratory diseases among older adults. Subjects were collected from the Longitudinal Health Insurance Database in Taiwan. The cumulative degree hours (CDHs) was used to assess the cumulative effect of indoor temperature exposure. A distributed lag nonlinear model with quasi-Poisson function was used to analyze the association between CDHs and emergency department visits due to IRD and NIRD. For IRD, there was a significant risk at 27, 28, 29, 30, and 31 °C when the CDHs exceeded 69, 40, 14, 5, and 1 during the cooling season (May to October), respectively, and at 19, 20, 21, 22, and 23 °C when the CDHs exceeded 8, 1, 1, 35, and 62 during the heating season (November to April), respectively. For NIRD, there was a significant risk at 19, 20, 21, 22, and 23 °C when the CDHs exceeded 1, 1, 16, 36, and 52 during the heating season, respectively; the CDHs at 1 was only associated with the NIRD at 31 °C during the cooling season. Our data also indicated that the CDHs was lower among men than women. We conclude that the cumulative effects of indoor temperature exposure should be considered to reduce IRD risk in both cooling and heating seasons and NIRD risk in heating season and the cumulative effect on different gender.

Emergency room visits for childhood atopic dermatitis are associated with floods?

Floods are known to increase the level of allergens such as molds in the environments. Under climate change, the frequency of floods could be increased, which highlights the importance of understanding the impacts of floods on atopic diseases. However, there was a lack of studies. This study examines whether floods induce attacks of childhood atopic dermatitis (AD). A retrospective population-based study was conducted in Taiwan Island using Taiwan's National Health Insurance Research Database. Emergency room (ER) visits for AD were identified among children aged 0-12 years. Weekly data of flood occurrence, number of flood sites, temperature, and air pollution were obtained for each township of the identified cases. A time-stratified case-crossover design was used. The relationship between ER visits for AD and floods was assessed by conditional logistic regression, adjusting for weekly mean temperature, PM2.5 and NO2. There were a total of 55,488 ER visits due to AD during the study period. Such visits increased when flood occurred, and then declined. The effects of floods at the week of flood remained robust, with OR of 1.14 (95% CI = 1.01-1.28) for flood occurrence and 1.31 (95% CI = 1.10-1.55) for the number of flood sites, after adjusting for covariates. Such effects were slightly higher in boys and children aged 1-12 years. This study demonstrated the impact of floods on flare-up of childhood AD, and the effect was most prominently at the week of flood. Healthcare workers should be alarmed for potential increase of AD flare ups after flood events.

Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy.

BACKGROUND: Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases. RESULTS: Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children's respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (ß = - 1.75, p = 0.015) after adjustment for child's sex, age, BMI, parents' smoking status, allergic history, and education levels, PM2.5, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65-0.99). CONCLUSIONS: Exposure to BBzP in settled dust might increase children's respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.

Using a land use regression model with machine learning to estimate ground level PM2.5.

Ambient fine particulate matter (PM2.5) has been ranked as the sixth leading risk factor globally for death and disability. Modelling methods based on having access to a limited number of monitor stations are required for capturing PM2.5 spatial and temporal continuous variations with a sufficient resolution. This study utilized a land use regression (LUR) model with machine learning to assess the spatial-temporal variability of PM2.5. Daily average PM2.5 data was collected from 73 fixed air quality monitoring stations that belonged to the Taiwan EPA on the main island of Taiwan. Nearly 280,000 observations from 2006 to 2016 were used for the analysis. Several datasets were collected to determine spatial predictor variables, including the EPA environmental resources dataset, a meteorological dataset, a land-use inventory, a landmark dataset, a digital road network map, a digital terrain model, MODIS Normalized Difference Vegetation Index (NDVI) database, and a power plant distribution dataset. First, conventional LUR and Hybrid Kriging-LUR were utilized to identify the important predictor variables. Then, deep neural network, random forest, and XGBoost algorithms were used to fit the prediction model based on the variables selected by the LUR models. Data splitting, 10-fold cross validation, external data verification, and seasonal-based and county-based validation methods were used to verify the robustness of the developed models. The results demonstrated that the proposed conventional LUR and Hybrid Kriging-LUR models captured 58% and 89% of PM2.5 variations, respectively. When XGBoost algorithm was incorporated, the explanatory power of the models increased to 73% and 94%, respectively. The Hybrid Kriging-LUR with XGBoost algorithm outperformed the other integrated methods. This study demonstrates the value of combining Hybrid Kriging-LUR model and an XGBoost algorithm for estimating the spatial-temporal variability of PM2.5 exposures.