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.

Hepatocellular carcinoma-related cyclin D1 is selectively regulated by autophagy degradation system.

Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic microRNA (miR)-224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy-selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33-238 R) and phosphorylation site (T286A) mutants, lentivirus-mediated silencing autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy-selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. CONCLUSION: Taken together, our data demonstrate that autophagic degradation machinery and the cell-cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141-154).

Association Between Long-term Exposure to PM2.5 and Incidence of Type 2 Diabetes in Taiwan: A National Retrospective Cohort Study.

BACKGROUND: Long-term exposure to fine particulate matter (PM with an aerodynamic diameter ≤2.5 µm; PM2.5) contributes to an elevated incidence of type 2 diabetes (T2D) in North America and Europe, but there is limited empirical evidence for Asian countries. This study determined the association between and the exposure-response relationship for PM2.5 and the incidence of T2D in Taiwan. METHODS: This retrospective cohort study was conducted for the years 2001-2012. Health information, including age, sex, health insurance premium, type of occupation, medication, and disease status, was retrieved from the Longitudinal Health Insurance Database 2000. Monitoring data for PM2.5 came from the Environmental Protection Administration of Taiwan, and Land-use Regression modeling was used to approximate participants' long-term exposure to PM2.5. Cox proportional hazards models with a generalized estimating equation to account for the correlation within the locations of the medical facilities were used to estimate the association between exposure to PM2.5 and the incidence of T2D, adjusting for the potential confounders. We also examined effect modification of sex, age, hyperlipidemia, and National Health Insurance premium for the association. RESULTS: Forty-eight thousand six hundred eleven new cases of diabetes were identified among 505,151 eligible participants, with the median follow-up of 12 years. Positive associations were identified between long-term exposure to PM2.5 exposure and the incidence of T2D. An increase of 10 µg/m PM2.5 was associated with an 11.0% increase in the risk of contracting diabetes (95% confidence interval = 8.0%, 13.0%). The results show that there is an almost linear relationship between exposure to PM2.5 and the incidence of T2D. Sex, age, hyperlipidemia, and National Health Insurance premium acted as effect modifiers of the association between diabetes incidence and levels of PM2.5 exposure in Taiwan. CONCLUSIONS: In the population in Taiwan, long-term exposure to PM2.5 increases the risk of incidence of T2D by 11%. This effect is more pronounced in elderly male patients who exhibit hyperlipidemia and in individuals who have a lower insurance health insurance premium.

Higher moisture content is associated with greater emissions of DEHP from PVC wallpaper.

Water damage and moisture in buildings may become more prevalent due to the increasing frequency of extreme precipitation and flooding events resulting from climate change. However, the effects of moisture levels on phthalate emissions from building materials are still underreported. This study aims to evaluate the effect of moisture content (MC) on the level of di-(2ethylhexyl) phthalate (DEHP) emitted from plastic wallpaper (0.22wt% DEHP) within 15 days in a closed chamber. A scenario of short-term exposure to DEHP in buildings suffering from water damage was simulated. Experiments, controlled at 100% relative humidity (RH) of air and 28°C, were conducted under the following three conditions: (I) without wallpaper (control chamber), (II) dry wallpaper (MC at 3.57%) and (III) damp wallpaper (MC at 52.31%). Air and dust samples were collected at the elapsed time of 2, 4, 6, 8, 10, 13 and 15 days, and the wipe sample was collected on the last day. Higher DEHP concentrations were found to be emitted into the air and adsorbed on the dust for wallpapers with higher MC%. DEHP levels in the air exhibited an increasing trend with the length of the experiment. Overall, it was found that approximately 35.31% more total DEHP mass was released into the air, dust and wipe samples from damp wallpapers compared to dry wallpapers. It is concluded that DEHP emissions from plastic materials are affected by the inner moisture percentage.

Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury.

The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury.

Explainable geospatial-artificial intelligence models for the estimation of PM2.5 concentration variation during commuting rush hours in Taiwan.

PM2.5 concentrations are higher during rush hours at background stations compared to the average concentration across these stations. Few studies have investigated PM2.5 concentration and its spatial distribution during rush hours using machine learning models. This study employs a geospatial-artificial intelligence (Geo-AI) prediction model to estimate the spatial and temporal variations of PM2.5 concentrations during morning and dusk rush hours in Taiwan. Mean hourly PM2.5 measurements were collected from 2006 to 2020, and aggregated into morning (7 a.m.-9 a.m.) and dusk (4 p.m.-6 p.m.) rush-hour mean concentrations. The Geo-AI prediction model was generated by integrating kriging interpolation, land-use regression, machine learning, and a stacking ensemble approach. A forward stepwise variable selection method based on the SHapley Additive exPlanations (SHAP) index was used to identify the most influential variables. The performance of the Geo-AI models for morning and dusk rush hours had accuracy scores of 0.95 and 0.93, respectively and these results were validated, indicating robust model performance. Spatially, PM2.5 concentrations were higher in southwestern Taiwan for morning rush hours, and suburban areas for dusk rush hours. Key predictors included kriged PM2.5 values, SO2 concentrations, forest density, and the distance to incinerators for both morning and dusk rush hours. These PM2.5 estimates for morning and dusk rush hours can support the development of alternative commuting routes with lower concentrations.

Anti-influenza A (H1N1) virus effect of gallic acid through inhibition of virulent protein production and association with autophagy.

Influenza remains one of the most serious infectious diseases. Gallic acid is one of the most common and representative phenolic acids found in various plants. This is an interesting subject to explore how gallic acid could inhibit H1N1 influenza virus infection by reducing the production of virulent proteins and interrupting autophagy machinery for influenza virus replication on the host cell. Cellular viability was assessed by XTT assay. The inhibitory effects on the H1N1 influenza virus were assessed by hemagglutination assay, plaque assay, and qRT-PCR. Western blot analysis was used for detecting protein levels of M1, M2, NP, LC3B, and beclin-1. Autophagy activity was demonstrated by acridine orange staining assay. The result demonstrated that there was no cytotoxic effect of gallic acid on A549 cells, and gallic acid could restore the cellular viability of H1N1 influenza virus-infected A549 cells within the experimental concentration treatment. Moreover, gallic acid could effectively restrain viral activity of the H1N1 influenza virus. After the treatment of gallic acid, the production of virulent H1N1 influenza virus proteins, that is, M1, M2, and NP protein were reduced. As for autophagic mechanism, both of the LC3B II conversion and the level ratio of LC3B II to LC3B I were notably decreased. The acridine orange staining assay also revealed decreased accumulation of autophagosomes in H1N1 influenza virus-infected cells. In conclusion, gallic acid suppresses H1N1 influenza viral infectivity through restoration of autophagy pathway and inhibition of virulent M1, M2, and NP protein production.

Hyperuricemia after exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans near a highly contaminated area.

BACKGROUND: Hyperuricemia (too much uric acid in the blood) is the predisposing condition for gout and is associated with hypertriglyceridemia, diabetes mellitus, and coronary artery disease. Polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) cause renal toxicity and elevate uric acid. The aim of this analysis was to investigate and clarify the effect of moderate-to-high PCDD/F exposure on hyperuricemia risk. METHODS: In this cross-sectional study, we recruited 1531 healthy participants living near a deserted pentachlorophenol factory. We measured serum levels of 17 2,3,7,8-substituted PCDD/Fs, and then examined associations between the main predictor variable, serum TEQ(DF-2005) (total PCDD/Fs 2005 World Health Organization [WHO] toxic equivalency [TEQ]), and dependent variables such as uric acid, glomerular filtration rates, and hyperuricemia risk. RESULTS: We observed a strong monotonic inverse relationship between serum TEQ(DF-2005) quartiles and the estimated glomerular filtration rate after adjusting for confounding factors (Men: ß were 0, -4.7, -6.2, and -14.8; Women: ß were 0, -6.7, -12.9, and -21.5). In addition, we observed a suggestive positive trend between serum TEQDF-2005 quartiles and uric acid only in men after adjusting for confounding factors (Men: ß were 0, 0.40, 0.36, and 0.59; P for trend <0.05). Men with serum TEQ(DF-2005) higher than the reference group's (<7.4 pg WHO(2005)-TEQ(DF/g) lipid) had a higher hyperuricemia risk after adjusting for confounding factors (25th to <50th percentile, adjusted odds ratio [AOR] = 2.20 [95% confidence interval {CI} = 1.30-3.73]; 50th to <75th percentile, AOR = 1.86 [95% CI = 1.08-3.22]; ≥ 75th percentile, AOR = 3.00 [95% CI = 1.69-5.31]). CONCLUSIONS: We conclude that serum TEQ(DF-2005) is an important determinant of serum uric acid levels and heightens the risk of hyperuricemia in general populations.

A positive relationship between ambient temperature and bipolar disorder identified using a national cohort of psychiatric inpatients.

OBJECTIVE: This study characterizes the positive relationship between daily temperature and bipolar disorder in a cohort of Taiwanese psychiatric inpatients. METHODS: Meteorological data, provided by the Central Weather Bureau (CWB) of Taiwan, were interpolated to create representative estimates of mean diurnal temperatures for 352 townships. Psychiatric inpatient admissions enrolled in the national health-care insurance system were retrieved from the 1996-2007 Psychiatric Inpatient Medical Claim (PIMC) dataset. The generalized linear mixed models with Poisson distribution were used to evaluate the relative risks of mean diurnal temperature with respect to increased admissions for bipolar disorder, while adjusting for internal correlations and demographic covariates. RESULTS: Increased relative risks of bipolar disorder admissions were associated with the increasing trends of temperature over 24.0 °C (50th ‰), especially for adults and females. The highest daily diurnal temperatures above 30.7 °C (99th ‰) had the greatest risks of bipolar hospitalizations. CONCLUSION: Understanding the increase of bipolar disorder admissions occurring in extreme heat is important in the preparation and prevention of massive recurrences of bipolar episodes.

An ensemble mixed spatial model in estimating long-term and diurnal variations of PM2.5 in Taiwan.

Meteorology, human activities, and other emission sources drive diurnal cyclic patterns of air pollution. Previous studies mainly focused on the variation of PM2.5 concentrations during daytime rather than nighttime. In addition, assessing the spatial variations of PM2.5 in large areas is a critical issue for environmental epidemiological studies to clarify the health effects from PM2.5 exposures. In terms of air pollution spatial modelling, using only a single model might lose information in capturing spatial and temporal correlation between predictors and pollutant levels. Hence, this study aimed to propose an ensemble mixed spatial model that incorporated Kriging interpolation, land-use regression (LUR), machine learning, and stacking ensemble approach to estimate long-term PM2.5 variations for nearly three decades in daytime and nighttime. Three steps of model development were applied: 1) linear based LUR and Hybrid Kriging-LUR were used to determine influential predictors; 2) machine learning algorithms were used to enhance model prediction accuracy; 3) predictions from the selected machine learning models were fitted and evaluated again to build the final ensemble mixed spatial model. The results showed that prediction performance increased from 0.514 to 0.895 for daily, 0.478 to 0.879 for daytime, and 0.523 to 0.878 for nighttime when applying the proposed ensemble mixed spatial model compared with LUR. Results of overfitting test and extrapolation ability test confirmed the robustness and reliability of the developed models. The distance to the nearest thermal power plant, density of soil and pebbles fields, and funeral facilities might affect the variation of PM2.5 levels between daytime and nighttime. The PM2.5 level was higher in daytime compared with nighttime with little difference, revealing the importance of estimating nighttime PM2.5 variations. Our findings also clarified the emission sources in daytime and nighttime, which serve as valuable information for air pollution control strategies establishment.

Feeding bottles usage and the prevalence of childhood allergy and asthma.

This study aimed to examine the association between the length of use of feeding bottles or pacifiers during childhood and the prevalence of respiratory and allergic morbidities. A large-scale questionnaire survey was performed in day care centers and kindergartens (with children's ages ranging from 2 to 7 years) in southern Taiwan, and a total of 14,862 questionnaires completed by parents were finally recruited for data analysis. Effects of using feeding bottles on children's wheezing/asthma (adjusted OR: 1.05, 95% CI 1.00-1.09), allergic rhinitis (adjusted OR: 1.04, 95% CI 1.00-1.08), and eczema (adjusted OR: 1.07, 95% CI 1.01-1.2) were found. Moreover, significant dose-dependent relationships were further established after an adjustment for confounders was performed that included children's ages, gender, gestational age, birth weight, length of breastfeeding, the age when first given infant formula or complementary foods, family history, parental educational levels, and smoking status, as well as the problem of indoor water damage. This study was the first to reveal the potential risk of using plastic consumer products such as feeding bottles on the reported health status of preschool children in Asian countries.

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.

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.

Exploring the Potential Relationship Between Global Greenness and DALY Loss Due to Depressive Disorders.

Objective: Prior studies have shown that greenness can reduce the burden of depressive disorders. However, most were focused on local-scale analyses while limited evaluated globally. We aimed to investigate the association between greenness and the burden of depressive disorders using data from 183 countries worldwide. Methods: We used the normalized difference vegetation index (NDVI) to estimate greenness. Country-level disability-adjusted life year (DALY) loss due to depressive disorders was used to represent depressive disorder burdens. A generalized linear mixed model was applied to assess the relationship between greenness and depressive disorders after controlling for covariates. Stratified analyses were conducted to determine the effects of greenness across several socio-demographic levels. Results: The findings showed a significant negative association between greenness and the health burden of depressive disorders with a coefficient of -0.196 (95% CI: -0.356, -0.035) in the DALY changes per interquartile unit increment of NDVI. The stratified analyses suggested beneficial effects of greenness on depressive disorders across sex, various age groups especially for those aged <49 years, with low-income and/or those living in highly urbanized countries. Conclusions: Our study noted that greenness exposure was significant negative association with the burden of depressive disorders. The findings should be viewed as recommendations for relevant authorities in supporting environmental greenness enhancement to reduce the mental burdens.

Examining the Benefits of Greenness on Reducing Suicide Mortality Rate: A Global Ecological Study.

Objective: This study applied an ecological-based analysis aimed to evaluate on a global scale the association between greenness exposure and suicide mortality. Methods: Suicide mortality data provided by the Institute for Health Metrics and Evaluation and the Normalized Difference Vegetation Index (NDVI) were employed. The generalized additive mixed model was applied to evaluate with an adjustment of covariates the association between greenness and suicide mortality. Sensitivity tests and positive-negative controls also were used to examine less overt insights. Subgroup analyses were then conducted to investigate the effects of greenness on suicide mortality among various conditions. Results: The main finding of this study indicates a negative association between greenness exposure and suicide mortality, as greenness significantly decreases the risk of suicide mortality per interquartile unit increment of NDVI (relative risk = 0.69, 95%CI: 0.59-0.81). Further, sensitivity analyses confirmed the robustness of the findings. Subgroup analyses also showed a significant negative association between greenness and suicide mortality for various stratified factors, such as sex, various income levels, urbanization levels, etc. Conclusions: Greenness exposure may contribute to a reduction in suicide mortality. It is recommended that policymakers and communities increase environmental greenness in order to mitigate the global health burden of suicide.

Novel Aporphine- and Proaporphine-Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula with Strong Anti-DENV2 Activity.

Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C-C or N-C covalent linkage. Here, we report four structurally attractive diterpene-alkaloid conjugates polyalongarins A-D (1-4), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of 1. Compounds 1-4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC50 (2.8-6.4 µM) and CC50 values (50.4-200 µM). The inhibitory mechanism of 1-4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1-4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane-aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.

Cardiovascular mortality during heat and cold events: determinants of regional vulnerability in Taiwan.

OBJECTIVES: To identify the vulnerable regions with underlying susceptibility and poor adaptive capability in response to cold and heat events in Taiwan, and to characterise the determinants associated with such an increasing risk to design better adaptive strategies in view of predicted weather changes in the future. METHODS: The authors used spatial regression models to measure the relationships between the spatial characteristics of temperature, extracted factors from demographic and socio-economic parameters, and the mean cardiovascular mortality 2 weeks before and after cold or heat events from 1994 to 2003. RESULTS: Metropolitan regions were found to have a substantially lower mortality than rural areas after cold and heat events. Events of cold, compared with heat, had greater impacts on the mortality ratio in most townships. A negative association was identified, using a spatial lag model, between the mortality after cold and heat events and urbanisation, and the availability of medical resources. A higher percentage of older people, vulnerable and aborigines might have contributed to the increasing vulnerability of townships during cold and heat events. CONCLUSIONS: These data, using an island-wide spatial analysis, suggest that urban areas have a greater adaptive capability than rural areas, plausibly because people in urban areas have a higher socio-economic status and more medical resources. Social inequality across urban and rural townships is apparent and developing customised adaptation programmes for vulnerable regions to cope with heat and cold event should be prioritised.

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.

Residential green space structures are associated with a lower risk of bipolar disorder: A nationwide population-based study in Taiwan.

Although many researchers have identified the potential psychological benefits offered by greenness, the association between green space structures and mental disorders is not well understood. The purpose of this study was to identify associations between green space structures and the incidence of bipolar disorder. To this end, we investigated 1,907,776 individuals collected from Taiwan's National Health Insurance Research Database. After a follow-up investigation from 2005 to 2016, among those with no history of bipolar disorder, 20,548 individuals were further found to be diagnosed with bipolar disorder. A geographic information system and landscape index were used to quantify three indices of green space structures: mean patch area (area and edge), mean fractal dimension index (shape), and mean proximity index (proximity). Additionally, greenness indices, the normalized difference vegetation index, and the enhanced vegetation index were used to confirm the association between greenness and incidence of bipolar disorder. These five indices were used to represent the individual's exposure according to the township of the hospital that they most frequently visited with symptoms of the common cold. Spearman's correlation analysis was performed to select variables by considering their collinearity. Subsequently, the frailty model for each index was used to examine the specific associations between those respective indices and the incidence of bipolar disorder by adjusting for related risk factors, such as socioeconomic status, metabolic syndrome, and air pollution. A negative association was identified between the mean patch area and the mean proximity index, and the incidence of bipolar disorder. In contrast, a positive association was found between the mean fractal dimension index and the incidence of bipolar disorder. We observed similar results in sensitivity testing and subgroup analysis. Exposure to green spaces with a larger area, greater proximity, lower complexity, and greener area may reduce the risk of bipolar disorder.