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Chih-Kuang Chen,1 Ping-Kuan Huang,2 Wing-Cheung Law,3 Chia-Hui Chu,4 Nai-Tzu Chen,5 Leu-Wei Lo4 1Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan; 2Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan; 3Department of Industrial and Systems Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China; 4Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 35053, Taiwan; 5Institute of New Drug Development, China Medical University, Taichung 40402, TaiwanCorrespondence: Chih-Kuang ChenDepartment of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanTel +886-7-5252000 ext. 4060Fax +886-7-5254099Email chihkuan@mail.nsysu.edu.twLeu-Wei LoInstitute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 35053, TaiwanTel +886-37-246166 ext. 37115Email lwlo@nhri.org.twAbstract: Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral- and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given.Keywords: gene therapy, gene delivery, non-viral vectors, polymeric vectors, biodegradable polymers

Nai-Tzu Chen,1 Eugene D Barth,2,3 Tsung-Hsi Lee,4 Chin-Tu Chen,5 Boris Epel,2,3 Howard J Halpern,2,3 Leu-Wei Lo5,61Institute of New Drug Development, China Medical University, Taichung 40402, Taiwan; 2Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA; 3Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, IL 60637, USA; 4Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan; 5Department of Radiology, University of Chicago, Chicago, IL 60637 USA; 6Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 35053, TaiwanPurpose: Tumor oxygenation is a critical parameter influencing the efficacy of cancer therapy. Low levels of oxygen in solid tumor have been recognized as an indicator of malignant progression and metastasis, as well as poor response to chemo- and radiation therapy. Being able to measure oxygenation for an individual’s tumor would provide doctors with a valuable way of identifying optimal treatments for patients.Methods: Electron paramagnetic resonance imaging (EPRI) in combination with an oxygen-measuring paramagnetic probe was performed to measure tumor oxygenation in vivo. Triarylmethyl (trityl) radical exhibits high specificity, sensitivity, and resolution for quantitative measurement of O2 concentration. However, its in vivo applications in previous studies have been limited by the required high dosage, its short half-life, and poor intracellular permeability. To address these limitations, we developed high-capacity nanoformulated radicals that employed fluorescein isothiocyanate-labeled mesoporous silica nanoparticles (FMSNs) as trityl radical carriers. The high surface area nanostructure and easy surface modification of physiochemical properties of FMSNs enable efficient targeted delivery of highly concentrated, nonself-quenched trityl radicals, protected from environmental degradation and dilution.Results: We successfully designed and synthesized a tumor-targeted nanoplatform as a carrier for trityl. In addition, the nanoformulated trityl does not affect oxygen-sensing capacity by a self-relaxation or broadening effect. The FMSN-trityl exhibited high sensitivity/response to oxygen in the partial oxygen pressure range from 0 to 155 mmHg. Furthermore, MSN-trityl displayed outstanding intracellular oxygen mapping in both in vitro and in vivo animal studies.Conclusion: The highly sensitive nanoformulated trityl spin probe can profile intracellular oxygen distributions of tumor in a real-time and quantitative manner using in vivo EPRI.Keywords: tumor oxygenation, electron paramagnetic resonance imaging (EPRI), mesoporous silica nanoparticles (MSNs), triarylmethyl (trityl) spin probe

Microplastics (MPs) have been widely detected in agricultural soils, and agricultural activities have been identified as an important factor influencing the abundance of MPs in the air. However, no studies have investigated whether agricultural activities are contributors to airborne MPs in buildings near farms. We collected airborne MP samples using an active sampling method from an elementary school near corn farms during different cultivation stages to assess the impact of agricultural activities on MPs in the study school near farms. Our data showed that the predominant shapes, sizes, colors, and polymer compositions were fragments, 2-50 μm, black or grey, and polyethylene terephthalate, respectively, during all cultivation stages. The highest and lowest MP concentrations were recorded during the land preparation (56.8 ± 7.4 particles/m 3 , August 2022) and growth (2.5 ± 1.8 particles/m 3 , February 2022) stages, respectively. A multiple-path particle dosimetry model revealed that the deposition fractions of MPs in humans were highest in the head; the highest and lowest deposition rates and fluxes of MPs in the airway were found during the land preparation and growth stages, respectively. The concentration of MPs did not present a positive correlation with potassium or crustal elemental concentration; however, it did show a positive association with temperature value. Therefore, our data did not show that corn cultivation influences MP concentrations in the study school near corn farms; instead, temperature was an important influencing factor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: MELD 3.0 introduces changes to address waitlist disparities for liver transplant (LT) candidates. Ascites and hepatic encephalopathy (HE) are important milestones in the natural history of cirrhosis regardless of the Model for End-Stage Liver Disease (MELD) score. We aim to assess the impact of ascites and HE and its interaction with MELD 3.0 on waitlist mortality., Methods: This is a retrospective study of patients listed for LT in the Organ Procurement and Transplantation Network database from 2016 to 2021. The primary outcome was waitlist mortality (death/delisting for too sick to LT). Ascites/HE were classified as moderate ascites without moderate HE (mAscites), moderate HE without moderate ascites (mHE), both moderate ascites/HE (mBoth), and neither. MELD 3.0 scores were categorized as <20, 20-29, 30-39, and ≥40., Results: Of 39 025 candidates, 29% had mAscites, 3% mHE, and 8% mBoth. One-year waitlist mortality was 30%, 38%, and 47%, respectively, compared with 17% (all P  < 0.001) for those with neither. In multivariable Cox regression, the adjusted risk of waitlist mortality associated with mAscites (versus neither) was a hazard ratio (HR) of 1.76 (95% confidence interval [CI], 1.55-2.00) when the MELD 3.0 score was <20, significantly higher than when the MELD 3.0 score was 20-29 (HR 1.40; 95% CI, 1.27-1.54), 30-39 (HR 1.19; 95% CI, 1.04-1.35), and ≥40 (HR 1.14; 95% CI, 0.91-1.43, interaction P  < 0.05 for all). A similar pattern was observed by MELD 3.0 for both moderate ascites/HE., Conclusions: The presence of moderate ascites alone, or combined with moderate HE, not only increases the risk of waitlist mortality but also has a differential effect by MELD 3.0, especially at lower MELD scores. Earlier strategies addressing this group and improving treatment plans or access to LT regardless of MELD remain needed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Tetranucleotide repeat domain protein 39B (TTC39B) was found to combine with ubiquitin ligase E3, and promote the ubiquitination modification of liver X receptor (LXR), which led to the inhibition of reverse cholesterol transport and development of atherosclerosis. QiShenYiQi pill (QSYQ) is a modern Chinese patent drug for treating ischemic cardiovascular diseases, the underlying mechanism is found to promote the expression of LXR-α/ ATP-binding cassette transporter G5 (ABCG5) in the liver of atherosclerotic mice., Purpose: The aim of this study is to investigate the effect of QSYQ on TTC39B-LXR mediated reverse cholesterol transport in atherosclerotic mice., Study Design and Methods: Male apolipoprotein E gene knockout mice (7 weeks old) were fed with high-fat diet and treated with low dose of QSYQ (QSYQ-l, 0.3 g/kg·d), high dose of QSYQ (QSYQ-H, 1.2 g/kg·d) and LXR-α agonist (LXR-A, GW3965 10 mg/kg·d) for 8 weeks. C57BL/6 J mice were fed with normal diet and used as negative control. Oil red O staining, HE staining, ELISA, RNA sequencing, western blot, immunohistochemistry, RT-PCR, cell culture and RNA interference were performed to analyze the effect of QSYQ on atherosclerosis., Results: HE staining showed that QSYQ reduced the atherosclerotic lesion significantly when compared to the control group. ELISA measurement showed that QSYQ decreased serum VLDL and increased serum ApoA1. Oil Red O staining showed that QSYQ reduced the lipid content of liver and protect liver function. Comparative transcriptome RNA-sequence of liver showed that DEGs after QSYQ treatment enriched in high-density lipoprotein particle, ubiquitin ligase complex, bile secretion, etc. Immunohistochemical staining and western blot proved that QSYQ increased the protein expression of hepatic SR-B1, LXR-α, LXR-β, CYP7A1 and ABCG5. Targeted inhibiting Ttc39b gene in vitro further established that QSYQ inhibited the gene expression of Ttc39b, increased the protein expression of SR-B1, LXR-α/β, CYP7A1 and ABCG5 in rat hepatocyte., Conclusion: Our results demonstrated the new anti-atherosclerotic mechanism of QSYQ by targeting TTC39B-LXR mediated reverse cholesterol transport in liver. QSYQ not only promoted reverse cholesterol transport, but also improved fatty liver and protected liver function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Agricultural activity is an important source of particulate matter <2.5 μm in size (PM 2.5 ) in rural areas. In Taiwan, many elementary schools are surrounded by farms, and studies investigating the impact of agricultural activity on air quality in schools are required. We collected PM 2.5 samples from the classrooms of elementary schools near corn and rice farms during the crop cultivation stages and analyzed their concentrations and compositions to investigate whether agricultural activity affects the schools' air quality. We found that the average ratio of PM 2.5 /PM 10 (<10 μm in particle size) was <0.6 in the school near the corn farm, and that the indoor PM 2.5 /PM 10 ratio was significantly associated (r = 0.93, p < 0.05) with the outdoor ratio. Moreover, the potassium (K) concentration in the school near the corn farm (189.2 ± 119 ng/m 3 ) was higher than that near the rice farm (140.9 ± 116.0 ng/m 3 ). There were higher concentrations of K and crustal elements, and a greater crustal elements/heavy metals ratio, in the school near the corn farm during the sowing and soil covering stages than during other cultivation stages. Positive matrix factorization (PMF) results indicate that agricultural activity was a predominant contributor of PM 2.5 in the schools near corn and rice farms, however, PM 2.5 from industrial and traffic emissions also affected schools' air quality. In summary, agricultural activity influenced the air quality of schools, especially near the corn farm. Governments should develop air quality management policies to reduce the risk of children suffering exposure to high particle concentrations in these schools and further suggest that the impact of industrial and traffic emissions on air quality also requires attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

This work measured the δ 13 C and δ 15 N signatures in PM 2.5 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 PM 2.5 and size-segregated particles, respectively, for isotopic signatures analyses. Our data showed that both δ 13 C and δ 15 N values were heavier from incense stick burning (δ 13 C: 27.3 ± 0.5; δ 15 N: 8.63 ± 1.35) than cigarette (δ 13 C: 28.5 ± 0.2; δ 15 N: 4.15 ± 0.69). The scatter plots of δ 13 C and TC/PM 2.5 and of δ 15 N and TN/PM 2.5 can be applied to distinguish particle pollution sources and assess the influence of cigarette burning to PM 2.5 according to different nicotine contents. The δ 13 C values in size-segregated particles were similar to incense stick or cigarette burning; the δ 13 C values in PM 2.5 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 δ 15 N from incense stick and cigarette burning. These results suggest that the δ 13 C signatures on PM 2.5 cannot represent the isotopic characteristics of size-segregated particles and δ 15 N has limitation for pollution source identification of different particle sizes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 T 1 magnetic resonance imaging (MRI) contrast agent that can modulate oxygen in the tumor microenvironment via the catalytic conversion of H 2 O 2 to O 2 . The T 1 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 O 2 bubbles in the tumor by consuming H 2 O 2 ; 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 -1 s -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, T 1 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 T 1 MR imaging and oxygen modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sivasubramanian, Chu, Cheng, Chen, Chen, Chuang, Yu, Chen, Liao and Lo.)

Children are the sensitive population to fine particulate matter (PM 2.5 ) exposure and spend most of their time in bedroom. Infiltration factor (F inf ) can be used to calculate the fraction of total indoor PM 2.5 with outdoor origin to increase the accuracy of exposure assessment. However, studies have ignored the diurnal variations of PM 2.5 F inf values, and a few studies have estimated F inf values for heavy metals in PM 2.5 in children's bedrooms. To calculate the PM 2.5 F inf , real-time indoor and outdoor PM 2.5 concentrations and occupants' activities were collected in 56 study bedrooms. At 22 of the 56 study bedrooms, PM 2.5 samples were also collected for heavy metals analysis. We noted the PM 2.5 F inf 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 F inf 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 PM 2.5 and heavy metals F inf values are necessary to increase the accuracy of exposure assessment., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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, PM 2.5 and NO 2 . 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ambient fine particulate matter (PM 2.5 ) 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 PM 2.5 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 PM 2.5 . Daily average PM 2.5 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 PM 2.5 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 PM 2.5 exposures., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

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 (β =  - 1.75, p = 0.015) after adjustment for child's sex, age, BMI, parents' smoking status, allergic history, and education levels, PM 2.5 , 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.

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/m 3 , 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/m 3 , 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Photodynamic therapy (PDT), which involves the generation of reactive oxygen species (ROS) through interactions of a photosensitizer (PS) with light and oxygen, has been applied in oncology. Over the years, PDT techniques have been developed for the treatment of deep-seated cancers. However, (1) the tissue penetration limitation of excitation photon, (2) suppressed efficiency of PS due to multiple energy transfers, and (3) insufficient oxygen source in hypoxic tumor microenvironment still constitute major challenges facing the clinical application of PDT for achieving effective treatment. We present herein a PS-independent, ionizing radiation-induced PDT agent composed of yttrium oxide nanoscintillators core and silica shell (Y 2 O 3 :Eu@SiO 2 ) with an annealing process. Our results revealed that annealed Y 2 O 3 :Eu@SiO 2 could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y 2 O 3 :Eu@SiO 2 was demonstrated to enable the generation of electron-hole (e - -h + ) pairs in Y 2 O 3 under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y 2 O 3 :Eu@SiO 2 with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation ( S O 2 ) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y 2 O 3 :Eu@SiO 2 , achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y 2 O 3 :Eu@SiO 2 exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y 2 O 3 :Eu@SiO 2 concentration in vivo . With the pronounced X-RL for in-vivo imaging and dosimetry, it possesses significant potential for utilization as a precision theranostics producing highly efficient X-ray PDT for deep-seated tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

JAK2V617F is the most common mutation in patients with BCR-ABL negative myeloproliferative neoplasms (MPNs). The eradication of JAK2V617F hematopoietic stem cells (HSCs) is critical for achieving molecular remissions and cure. We investigate the distinct effects of two therapies, ruxolitinib (JAK1/2 inhibitor) and interferon-alpha (IFN-α), on the disease-initiating HSC population. Whereas ruxolitinib inhibits Stat5 activation in erythroid progenitor populations, it fails to inhibit this same pathway in HSCs. In contrast, IFN-α has direct effects on HSCs. Furthermore, STAT1 phosphorylation and pathway activation is greater after IFN-α stimulation in Jak2V617F murine HSCs with increased induction of reactive oxygen species, DNA damage and reduction in quiescence after chronic IFN-α treatment. Interestingly, ruxolitinib does not block IFN-α induced reactive oxygen species and DNA damage in Jak2V617F murine HSCs in vivo. This work provides a mechanistic rationale informing how pegylated IFN-α reduces JAK2V617F allelic burden in the clinical setting and may inform future clinical efforts to combine ruxolitinib with pegylated IFN-α in patients with MPN.

While altered gaze behaviour during facial emotion recognition has been observed in autistic individuals, there remains marked inconsistency in findings, with the majority of previous research focused towards the processing of basic emotional expressions. There is a need to examine whether atypical gaze during facial emotion recognition extends to more complex emotional expressions, which are experienced as part of everyday social functioning. The eye gaze of 20 autistic and 20 IQ-matched neurotypical adults was examined during a facial emotion recognition task of complex, dynamic emotion displays. Autistic adults fixated longer on the mouth region when viewing complex emotions compared to neurotypical adults, indicating that altered prioritization of visual information may contribute to facial emotion recognition impairment. Results confirm the need for more ecologically valid stimuli for the elucidation of the mechanisms underlying facial emotion recognition difficulty in autistic individuals.

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., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

This paper developed a land use regression (LUR) model to study the spatial-temporal variability of O₃ concentrations in Taiwan, which has typical Asian cultural characteristics with diverse local emission sources. The Environmental Protection Agency's (EPA) data of O₃ concentrations from 2000 and 2013 were used to develop this model, while observations from 2014 were used as the external data verification to assess model reliability. The distribution of temples, cemeteries, and crematoriums was included for a potential predictor as an Asian culturally specific source for incense and joss money burning. We used stepwise regression for the LUR model development, and applied 10-fold cross-validation and external data for the verification of model reliability. With the overall model R² of 0.74 and a 10-fold cross-validated R² of 0.70, this model presented a mid-high prediction performance level. Moreover, during the stepwise selection procedures, the number of temples, cemeteries, and crematoriums was selected as an important predictor. By using the long-term monitoring data to establish an LUR model with culture specific predictors, this model can better depict O₃ concentration variation in Asian areas.

Temperature was reported to have acute effects on mental disorders. However, the effect of long-term temperature exposure is unclear, especially in warmer regions. This research aimed to evaluate the association between long-term exposure to temperature and the incidence of major depressive disorder (MDD). A retrospective population-based study was conducted using Taiwan nationwide Longitudinal Health Insurance Database 2005. Subjects without MDD diagnosis were followed from 2003 to 2013 for MDD occurrence. Weather factors including temperature (°C), sunshine duration (hrs/day), and precipitation (mm/day) were 11-year average of daily data collected from weather monitoring stations of Taiwan Central Weather Bureau. Cox proportional hazard model was performed to examine the association between MDD incidence and weather factors. Covariates including age, gender, and insurance amount were adjusted. A total of 9,539,752 person-years were followed. People residing in regions with long-term temperature of 20-23 °C had the lowest risk of developing MDD. Risk for MDD incidence was higher among residents in regions with average temperature > 23 °C, at 7% increase per 1 °C increment (95% CI = 2-12%). The elderly was more vulnerable to such impact of heat exposure. For the elderly, males were more susceptible to heat-related MDD than females (HR = 1.18 vs. 1.14). However, the younger group showed a reverse finding (i.e. females 1.07 > males 1.04). Long-term residence in regions with extreme cold or heat may increase the risk of MDD incidence, especially higher temperature. Under global warming, these findings have great health implications and warrant further confirmation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

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.

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.

Background: Individuals with heightened anxiety vulnerability tend to preferentially attend to emotionally negative information, with evidence suggesting that this attentional bias makes a causal contribution to anxiety vulnerability. Recent years have seen an increase in the use of attentional bias modification (ABM) procedures to modify patterns of attentional bias; however, often this change in bias is not successfully achieved., Objective: This study presents a novel ABM procedure, Emotion-in-Motion, requiring individuals to engage in patterns of attentional scanning and tracking within a gamified, complex, and dynamic environment. We aimed to examine the capacity of this novel procedure, as compared with the traditional probe-based ABM procedure, to produce a change in attentional bias and result in a change in anxiety vulnerability., Methods: We administered either an attend-positive or attend-negative version of our novel ABM task or the conventional probe-based ABM task to undergraduate students (N=110). Subsequently, participants underwent an anagram stressor task, with state anxiety assessed before and following this stressor., Results: Although the conventional ABM task failed to induce differential patterns of attentional bias or affect anxiety vulnerability, the Emotion-in-Motion training did induce a greater attentional bias to negative faces in the attend-negative training condition than in the attend-positive training condition (P=.003, Cohen d=0.87) and led to a greater increase in stressor-induced state anxiety faces in the attend-negative training condition than in the attend-positive training condition (P=.03, Cohen d=0.60)., Conclusions: Our novel, gamified Emotion-in-Motion ABM task appears more effective in modifying patterns of attentional bias and anxiety vulnerability. Candidate mechanisms contributing to these findings are discussed, including the increased stimulus complexity, dynamic nature of the stimulus presentation, and enriched performance feedback., (©Lies Notebaert, Ben Grafton, Patrick JF Clarke, Daniel Rudaizky, Nigel TM Chen, Colin MacLeod. Originally published in JMIR Serious Games (http://games.jmir.org), 28.11.2018.)

This study investigated ambient volatile organic compounds (VOCs) and assessed excess health risks for child, adult and elderly populations in a residential area near a large-scale petrochemical complex in central Taiwan. A total of 155 daily VOC samples were collected in canisters from nine sites in spring, summer and winter during 2013-2014. We used a positive matrix factorization (PMF) model incorporating a conditional probability function (CPF) to quantify the potential sources of VOCs with the influences of local source directions. We then evaluated the non-cancer and cancer risks of specific VOCs with probabilistic distributions by performing a Monte-Carlo simulation for the child, adult, and elderly populations. Most of the VOCs were higher in summer than in winter or spring for the sampling sites. The presence of vinyl acetate, chloroethene, and 1,2-dichloroethane were significantly high within a 5-km radius of the petrochemical complex. Four potential sources of ambient VOCs, industrial emission (49.2%-63.6%), traffic-related emission (13.9%-19.1%), fuel evaporation (12.3%-16.9%), and aged emission (10.2%-14.8%), were identified. The cancer risk of ambient VOC exposure was mainly attributed to the industrial source in the study area, while the non-cancer risk was of less concern. Benzene associated with fuel evaporation resulted in the highest cancer risk (4.1 × 10 -5 -5.5 × 10 -5 ) as compared to that of the other toxic VOCs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

With more than 58,000 cases reported by the country's Centers for Disease Control, the dengue outbreaks from 2014 to 2015 seriously impacted the southern part of Taiwan. This study aims to assess the spatial autocorrelation of the dengue fever (DF) outbreak in southern Taiwan in 2014 and 2015, and to further understand the effects of green space (such as forests, farms, grass, and parks) allocation on DF. In this study, two different greenness indexes were used. The first green metric, the normalized difference vegetation index (NDVI), was provided by the long-term NASA MODIS satellite NDVI database, which quantifies and represents the overall vegetation greenness. The latest 2013 land use survey GIS database completed by the National Land Surveying and Mapping Center was obtained to access another green metric, green land use in Taiwan. We first used Spearman's rho to find out the relationship between DF and green space, and then three spatial autocorrelation methods, including Global Moran's I, high/low clustering, and Hot Spot were employed to assess the spatial autocorrelation of DF outbreak. In considering the impact of social and environmental factors in DF, we used generalized linear mixed models (GLMM) to further clarify the relationship between different types of green land use and dengue cases. Results of spatial autocorrelation analysis showed a high aggregation of dengue epidemic in southern Taiwan, and the metropolitan areas were the main hotspots. Results of correlation analysis and GLMM showed a positive correlation between parks and dengue fever, and the other five green space metrics and land types revealed a negative association with DF. Our findings may be an important asset for improving surveillance and control interventions for dengue.

Photodynamic therapy (PDT) is a cancer treatment that employs the production of cytotoxic reactive oxygen species (ROS), subsequently triggering tumor apoptosis and tumor size reduction. However, this approach suffers from insufficient light penetration depth. In order to mitigate this issue, pollen-structured gold clusters (PSGCs) were designed for mediating X-ray-induced PDT for radiotherapy enhancement. The structure of PSGCs provides a large surface area that is able to generate ROS upon X-ray irradiation. The synthesized PSGCs were exposed to different X-ray doses and the generated ROS was then quantified by dihydroethidium (DHE) assay. Furthermore, at the cellular level, the PDT efficacy of PSGCs was evaluated via immunofluorescence staining with &gamma;-H2AX and comet assay. The results demonstrated that PSGCs possess a significantly high ROS-generating capacity and a remarkable PDT efficacy in the treatment of breast cancer cells, thus showing potential clinical uses in deep-tissue cancer treatment., Competing Interests: The authors declare no conflicts of interest. The founding sponsors had no role in the design of the study; the collection, analysis, or interpretation of data; the writing of the manuscript; or the decision to publish the results.

Difficulties in Facial Emotion Recognition (FER) are commonly associated with individuals diagnosed with Autism Spectrum Disorder (ASD). However, the mechanisms underlying these impairments remain inconclusive. While atypical cortical connectivity has been observed in autistic individuals, there is a paucity of investigation during cognitive tasks such as FER. It is possible that atypical cortical connectivity may underlie FER impairments in this population. Electroencephalography (EEG) Imaginary Coherence was examined in 22 autistic adults and 23 typically developing (TD) matched controls during a complex, dynamic FER task. Autistic adults demonstrated reduced coherence between both short and long range inter-hemispheric electrodes. By contrast, short range intra-hemispheric connectivity was increased in frontal and occipital regions during FER. These findings suggest altered network functioning in ASD.

Viral aerosol infection through cough generates large amounts of viral aerosol and can result in many adverse health effects such as influenza flu and severe acute respiratory syndrome (SARS). To characterize the coughed viral aerosol, the sampler needs to sample at higher flow rate and possess high physical collection efficiency as well as high viral preservation. However, most current inertia-based high flow bioaerosol samplers are not suited for viral aerosol sampling since the viability will be lost doing the sampling process. Current condensation growth methods only have good physical collection efficiency and viral preservation at low flow rate (< 10 LPM). In this study, we developed a viral aerosol sampling system using a cooler and steam-jet aerosol collector (SJAC) for bioaerosol collection for the first time. The system is based on mixing condensation growth method and has high viral preservation at a higher flow rate (12.5 LPM). We control the inlet aerosol flow temperature and the SJAC mixing reservoir temperature to improve the physical collection efficiency and viability preservation of the viral aerosol. Results indicate that the physical collection efficiency is 70-99% for aerosol 30-100 nm when the aerosol flow and mixing reservoir temperature was 19 and 50 °C, respectively. In addition, the system was 7 and 22 times more efficient for viability preservation of MS2 bacteriophage than the commonly used All Glass Impinger 30 (AGI-30) and BioSampler®, respectively. Finally, the system can be applied to sample at a lower concentration (10 5 PFU/m 3 ), and results shows the system was 4.7 times more efficient for viability preservation than using AGI-30 alone. The developed viral collection system will improve our understanding of the characteristics of coughed aerosol and can be used for future evaluation of respiratory protective equipment and environmental sampling.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study systemically investigated the ambient PM 2.5 (n=108) with comprehensive analyses of the chemical composition, identification of the potential contributors, and estimation of the resultant respiratory physician visits in the residential regions near energy-consuming and high-polluting industries in central Taiwan. The positive matrix fraction (PMF) model with chemical profiles of trace metals, water-soluble ions, and organic/elemental carbons (OC/EC) was applied to quantify the potential sources of PM 2.5 . The influences of local sources were also explored using the conditional probability function (CPF). Associations between the daily PM 2.5 concentration and the risk of respiratory physician visits for the elderly (≥65years of age) were estimated using time-series analysis. A seasonal variation, with higher concentrations of PM 2.5 , metals (As, Cd, Sb, and Pb), OC/EC and ions (i.e., NO 3- , SO 4 2- and NH 4 + ) in the winter than in the spring and summer, was observed. Overall, an increase of 10μgm -3 in the same-day PM 2.5 was associated with an ~2% (95% CI: 1.5%-2.5%) increase in respiratory physician visits. Considering the health benefits of an effective reduction, we suggest that the emission from coal combustion (23.5%), iron ore and steel industry (17.1%), and non-ferrous metallurgy (14.4%), accounting for ~70% of the primary PM 2.5 in the winter are prioritized to control., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study investigates PM 2.5 -bound PAHs for rural sites (Dacheng and Fangyuan) positioned close to heavy air-polluting industries in Changhua County, central Taiwan. A total of 113 PM 2.5 samples with 22 PAHs collected from 2014 to 2015 were analyzed, and Positive Matrix Factorization (PMF) and diagnostic ratios of PAHs were applied to quantify potential PAH sources. The influences of local and regional sources were also explored using the conditional probability function (CPF) and potential source contribution function (PSCF) with PMF-modeled results, respectively. Annual mean concentrations of total PAHs were 2.91 ± 1.34 and 3.04 ± 1.40 ng/m 3 for Dacheng and Fangyuan, respectively, and their corresponding BaP eq were measured at 0.534 ± 0.255 and 0.563 ± 0.273 ng/m 3 in concentration. Seasonal variations with higher PAHs found for the winter than for the spring and summer were observed for both sites. The lifetime excess cancer risk (ECR) from inhalation exposure to PAHs was recorded as 4.7 × 10 -5 overall. Potential sources of PM 2.5 -bound PAHs include unburned petroleum and traffic emissions (42%), steel industry and coal combustion (31%), and petroleum and oil burning (27%), and unburned petroleum and traffic emission could contribute the highest ECR (2.4 × 10 -5 ). The CPF results show that directional apportionment patterns were consistent with the actual locations of local PAH sources. The PSCF results indicate that mainly northeastern regions of China have contributed elevated PM 2.5 -bound PAHs from long-range transports., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Theoretical models of social anxiety propose that attention biases maintain symptoms of social anxiety. Research findings regarding the time course of attention and social anxiety disorder have been mixed. Adult attachment style may influence attention bias and social anxiety, thus contributing to the mixed findings. This study investigated the time course of attention toward both negative and positive stimuli for individuals diagnosed with social anxiety disorder (SAD) and assessed whether attachment style moderates this relationship. One hundred and thirty participants (age: M=29.03) were assessed using a semistructured clinical interview. Those meeting eligibility criteria for the clinical sample met DSM-IV criteria for SAD (n=90, age: M=32.18), while those in the control sample did not meet criteria for any mental disorder (n=23, age: M=26.04, 11 females). All participants completed self-report measures examining depression, social anxiety, adult attachment style, and completed an eye-tracking task used to measure the time course of attention. Eye-tracking data were analysed using growth curve analysis. The results indicate that participants in the control group overall displayed greater vigilance towards emotional stimuli, were faster at initially fixating on the emotional stimulus, and had a greater percentage of fixations towards the emotional stimulus as the stimulus presentation time progressed compared to those in the clinical group. Thus, the clinical participants were more likely to avoid fixating on emotional stimuli in general (both negative and positive) compared to those in the control group. These results support the Clark and Wells (1995) proposal that socially anxious individuals avoid attending to emotional information. Attachment style did not moderate this association, however anxious attachment was related to greater vigilance toward emotional compared to neutral stimuli., (Copyright © 2016. Published by Elsevier Ltd.)

Major health behavior change models tend to consider health decisions as primarily resulting from a systematic appraisal of relevant beliefs, such as the perceived benefits and risks of a pharmacological intervention. Drawing on research from the disciplines of risk management, communication, and psychology, this study proposed the inclusion of a heuristic route in established theory and tested the direction of influence between heuristic and systematic process variables. Affect and social trust were included as key heuristics in the proposed dual-mode framework of health decision making. Furthermore, exposure to health-related coverage on television was considered potentially influential over both heuristic and systematic process variables. To test this framework, data were collected from a national probability sample of 584 adults in the United States in 2012 regarding their decision to vaccinate against a hypothetical avian flu. The results provided some support for the bidirectional influence between heuristic and systematic processing. Affect toward flu vaccination and trust in the Food and Drug Administration were found to be powerful predictors of vaccination intention, enhancing intention both directly and indirectly via certain systematic process variables. The direction of influence between perceived susceptibility and severity, on the one hand, and affect, on the other, is less clear, suggesting the need for further research. Contrary to the opinion of media critics, exposure to televised health coverage was negatively associated with the perceived risks of vaccination. Results from this study carry theoretical and practical implications, and applying this model to the acceptance of different health interventions constitutes an area for future inquiries., (© 2015 Society for Risk Analysis.)

Social anxiety disorder (SAD) is a debilitating mental illness which is thought to be maintained in part by the aberrant attentional processing of socially relevant information. Critically however, research has not assessed whether such aberrant attentional processing occurs during social-evaluative contexts characteristically feared in SAD. The current study presents a novel approach for the assessment of the visuocognitive biases operating in SAD during a social-evaluative stressor. For this task, clinically socially anxious participants and controls were required to give a brief impromptu speech in front of a pre-recorded audience who intermittently displayed socially positive or threatening gestures. Participant gaze at the audience display was recorded throughout the speech. Socially anxious participants exhibited a significantly longer visual scanpath, relative to controls. In addition, socially anxious participants spent relatively longer time fixating at the non-social regions in between and around the confederates. The findings of the present study suggest that SAD is associated with hyperscanning and the attentional avoidance of social stimuli., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Social anxiety is thought to be maintained by biased attentional processing towards threatening information. Research has further shown that the experimental attenuation of this bias, through the implementation of attentional bias modification (ABM), may serve to reduce social anxiety vulnerability. However, the mechanisms underlying ABM remain unclear. The present study examined whether inhibitory attentional control was associated with ABM. A non-clinical sample of participants was randomly assigned to receive either ABM or a placebo task. To assess pre-post changes in attentional control, participants were additionally administered an emotional antisaccade task. ABM participants exhibited a subsequent shift in attentional bias away from threat as expected. ABM participants further showed a subsequent decrease in antisaccade cost, indicating a general facilitation of inhibitory attentional control. Mediational analysis revealed that the shift in attentional bias following ABM was independent to the change in attentional control. The findings suggest that the mechanisms of ABM are multifaceted., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Legionnaires' disease (LD) is an acute form of pneumonia, and changing weather is considered a plausible risk factor. Yet, the relationship between weather and LD has rarely been investigated, especially using long-term daily data. In this study, daily data was used to evaluate the impacts of precipitation, temperature, and relative humidity on LD occurrence in Taiwan from 1995-2011. A time-stratified 2:1 matched-period case-crossover design was used to compare each case with self-controlled data using a conditional logistic regression analysis, and odds ratios (ORs) for LD occurrence was estimated. The city, gender and age were defined as a stratum for each matched set to modify the effects. For lag day- 0 to 15, the precipitation at lag day-11 significantly affected LD occurrence (p<0.05), and a 2.5% (95% CIs = 0.3-4.7%) increased risk of LD occurrence was associated with every 5-mm increase in precipitation. In addition, stratified analyses further showed that positive associations of precipitation with LD incidence were only significant in male and elderly groups and during the warm season ORs = 1.023-1.029). However, such an effect was not completely linear. Only precipitations at 21-40 (OR = 1.643 (95% CIs = 1.074-2.513)) and 61-80 mm (OR = 2.572 (1.106-5.978)) significantly increased the risk of LD occurrence. Moreover, a negative correlation between mean temperature at an 11-day lag and LD occurrence was also found (OR = 0.975 (0.953-0.996)). No significant association between relative humidity and LD occurrence was identified (p>0.05). In conclusion, in warm, humid regions, an increase of daily precipitation is likely to be a critical weather factor triggering LD occurrence where the risk is found particularly significant at an 11-day lag. Additionally, precipitation at 21-40 and 61-80 mm might make LD occurrence more likely.

Daily temperature measures are commonly used when examining the association between temperature and mortality. In fact, temperature measures are available 24 hours a day and more detailed records may provide a better prediction of mortality compared to daily statistics. In this article, monthly stratified analysis modeling for mortality is conducted for the total population as well as the stratified elderly and younger subgroups. We identified the most significant time during the day that is associated with daily mortality. Surprisingly, the estimates of relative risk and magnitude of associations derived from the hourly temperature measures are similar or even stronger compared to those modeled by the daily statistics. This phenomenon remains true for lagged hourly temperature measures and the changing patterns of associations from January through December are revealed. In summary, people are the most vulnerable to temperature variations in the early morning around 5 am and the night time around 8 pm.

Europium-doped yttrium oxide (Y 2 O 3 :Eu) has garnered considerable interest recently for its use as a highly efficient, red phosphor in a variety of lighting applications that include fluorescent lamps, plasma, and field emission display panels, light emitting diodes (LEDs), and lasers. In the present work, we describe the development of Y 2 O 3 :Eu nanoparticles for a very different application: in situ , in vivo x-ray dosimetry. Spectroscopic analyses of these nanoparticles during x-ray irradiation reveal surprisingly bright and stable radioluminescence at near-infrared wavelengths, with markedly linear response to changes in x-ray flux and energy. Monte Carlo modeling of incident flux and broadband, wide-field imaging of mouse phantoms bearing both Y 2 O 3 :Eu nanoparticles and calibrated LEDs of similar spectral emission demonstrated significant transmission of radioluminescence, in agreement with spectroscopic studies; with approximately 15 visible photons being generated for every x-ray photon incident. Unlike the dosimeters currently employed in clinical practice, these nanodosimeters can sample both dose and dose rate rapidly enough as to provide real-time feedback for x-ray based external beam radiotherapy (EBRT). The technique's use of remote sensing and absence of supporting structures enable perturbation-free dosing of the targeted region and complete sampling from any direction. With the conjugation of pathology-targeting ligands onto their surfaces, these nanodosimeters offer a potential paradigm shift in the real-time monitoring and modulation of delivered dose in the EBRT of cancer in situ .

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The unique optical properties of gold nanorods (GNRs) have recently drawn considerable interest from those working in in vivo biomolecular sensing and bioimaging. Especially appealing in these applications is the plasmon-enhanced photoluminescence of GNRs induced by two-photon excitation at infrared wavelengths, owing to the significant penetration depth of infrared light in tissue. Unfortunately, many studies have also shown that often the intensity of pulsed coherent irradiation of GNRs needed results in irreversible deformation of GNRs, greatly reducing their two-photon luminescence (TPL) emission intensity. In this work we report the design, synthesis, and evaluation of mesoporous silica-encased gold nanorods (MS-GNRs) that incorporate photosensitizers (PSs) for two-photon-activated photodynamic therapy (TPA-PDT). The PSs, doped into the nano-channels of the mesoporous silica shell, can be efficiently excited via intra-particle plasmonic resonance energy transfer from the encased two-photon excited gold nanorod and further generates cytotoxic singlet oxygen for cancer eradication. In addition, due to the mechanical support provided by encapsulating mesoporous silica matrix against thermal deformation, the two-photon luminescence stability of GNRs was significantly improved; after 100 seconds of 800 nm repetitive laser pulse with the 30 times higher than average power for imaging acquisition, MS-GNR luminescence intensity exhibited ~260% better resistance to deformation than that of the uncoated gold nanorods. These results strongly suggest that MS-GNRs with embedded PSs might provide a promising photodynamic therapy for the treatment of deeply situated cancers via plasmonic resonance energy transfer.

Research suggests that anxiety is maintained by an attentional bias to threat, and a growing base of evidence suggests that anxiety may additionally be associated with the deficient attentional processing of positive stimuli. The present study sought to examine whether such anxiety-linked attentional biases were associated with either stimulus driven or attentional control mechanisms of attentional selectivity. High and low trait anxious participants completed an emotional variant of an antisaccade task, in which they were required to prosaccade towards, or antisaccade away from a positive, neutral or threat stimulus, while eye movements were recorded. While low anxious participants were found to be slower to saccade in response to positive stimuli, irrespectively of whether a pro- or antisaccade was required, such a bias was absent in high anxious individuals. Analysis of erroneous antisaccades further revealed at trend level, that anxiety was associated with reduced peak velocity in response to threat. The findings suggest that anxiety is associated with the aberrant processing of positive stimuli, and greater compensatory efforts in the inhibition of threat. The findings further highlight the relevance of considering saccade peak velocity in the assessment of anxiety-linked attentional processing.

Mesoporous silica nanoparticles (MSNs), with their intrinsically large and easily functionalized surface areas and pore volumes, are particularly well-suited to efficient conveyance of a wide variety of therapeutic agents. When combined with other organic/inorganic nanomaterials, the resultant organic/inorganic-MSN hybrids demonstrate unique synergies and even greater versatility. In this paper, we describe the current status and future prospects of MSNs and organic/inorganic-MSN hybrids for combined therapeutic and diagnostic - theranostic - biomedical applications.

Cten is a focal adhesion molecule and a member of the tensin family. Its expression is highly enriched in the prostate and placenta, suggesting that cten gene might be closely associated with mammalian species. Recent studies have reported that cten expression is frequently up-regulated in a variety of cancers and its levels appear to correlate with tumorigenicity. Here, we have (1) analyzed cten sequences of various species to build a phylogenetic tree, (2) examined cten mRNA levels in human and mouse tissues to establish its expression profiles, and (3) determined the promoter region of human CTEN gene in cell lines and in a mouse model to understand its transcriptional regulation. Our analyses indicate that all currently known cten genes are present in mammals. The prostate and placenta are the two most cten abundant tissues in human and mouse, meanwhile brain and lung also express low levels of cten. Results from cell culture reporter assays demonstrate that a 327-bp fragment is the shortest functional promoter. All functional promoter constructs produce 40- to 160-fold increases in luciferase reporter activities in normal prostate cells, whereas lower activities (<40-fold) are detected in non-prostatic cell lines. To evaluate CTEN promoter activity in mice and develop a new tissue specific Cre recombinase mouse model, we have established pCTEN-Cre:R26R mice by crossing R26R β-galactosidase reporter mice with pCTEN-Cre transgenic mice, in which the 327-bp cten promoter drives the expression of Cre recombinase. X-gal analysis has shown strong β-galactosidase activities in the prostate, brain, and few other tissues in pCTEN-Cre:R26R mice. Altogether, we have identified the promoter region of human cten gene and provided a useful tool for investigating cell lineages and generating tissue-specific knockout or knockin mice., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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.

Purpose: Adults who stutter are at significant risk of developing social phobia. Cognitive theorists argue that a critical factor maintaining social anxiety is avoidance of social information. This avoidance may impair access to positive feedback from social encounters that could disconfirm fears and negative beliefs. Adults who stutter are known to engage in avoidance behaviours, and may neglect positive social information. This study investigated the gaze behaviour of adults who stutter whilst giving a speech., Method: 16 adults who stutter and 16 matched controls delivered a 3-min speech to a television display of a pre-recorded lecture theatre audience. Participants were told the audience was watching them live from another room. Audience members were trained to display positive, negative and neutral expressions. Participant eye movement was recorded with an eye-tracker., Results: There was a significant difference between the stuttering and control participants for fixation duration and fixation count towards an audience display. In particular, the stuttering participants, compared to controls, looked for shorter time at positive audience members than at negative and neutral audience members and the background., Conclusions: Adults who stutter may neglect positive social cues within social situations that could serve to disconfirm negative beliefs and fears., Educational Objectives: The reader will be able to: (a) describe the nature of anxiety experienced by adults who stutter; (b) identify the most common anxiety condition among adults who stutter; (c) understand how information processing biases and the use of safety behaviours contribute to the maintenance of social anxiety; (d) describe how avoiding social information may contribute to the maintenance of social anxiety in people who stutter; and (e) describe the clinical implications of avoidance of social information in people who stutter., (Copyright © 2012 Elsevier Inc. All rights reserved.)