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Tanavij Pannoi,1,2 Chissanupong Promchai,3 Penjamaporn Apiromruck,3 Suwikran Wongpraphairot,4 Chen-Chang Yang,1,5,6 Wen-Chi Pan1,5 1International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan; 2Department of Pharmaceutical Care, School of Pharmacy, Walailak University, Nakhon-Si-Thammarat, Thailand; 3Department of Pharmacy, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand; 4Department of Nephrology Unit, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand; 5Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei City, Taiwan; 6Department of Occupational Medicine and Clinical Toxicology, Taipei Veteran General Hospital, Taipei City, TaiwanCorrespondence: Wen-Chi Pan, Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, No. 155, Sec.2, Li-Nong St, Taipei City, 11221, Taiwan, Tel +886-228-267-000 #67057, Fax +886-2-28218165, Email wenchipan@nycu.edu.twPurpose: Potential adverse outcomes of Proton pump inhibitors (PPIs) have increasingly been reported. The potential risks to PPIs include hypomagnesemia and chronic kidney disease (CKD). Unlike a real-world electronic medical record (RW-EMR) with active-comparator design, claim databases and special population cohort with non-user design, using in previous studies, resulted in a wide range of strength of association with indication bias. This study aimed to measure the total effect of association between PPIs use and CKD incidence using Thai RW-EMR.Patients and Methods: A retrospective hospital-based cohort was applied into this study. Electronic medical records and administrative data of out- and inpatient were retrieved from October 1st, 2010 to September 30th, 2017. On-treatment with grace period as well as propensity score matching was used in data analysis. Cox proportional hazard models were applied to evaluate the PPIs-CKD association.Results: Of all 63,595 participants, a total of 59,477 new PPIs and 4118 Histamine 2-receptor antagonist (H2RA) users were eligible for follow-up. As compared with H2RA, the PPI users were non-elderly and more likely being female. The association of PPIs with CKD was statistically significant (adjusted hazard ratio [HR] = 3.753, 95% CI = 2.385– 5.905). The HR were not statistically different by concomitant use PPIs with NSAIDs and by medication possession ratio levels.Conclusion: The association between PPIs and CKD incidence was statistically significant in this hospital-based cohort. However, self-treatment with over-the-counter PPIs, as well as, smoking, drinking alcohol and body mass index could not be fully retrieved, affecting the estimation of treatment effect.Keywords: proton-pump inhibitors, chronic kidney disease, retrospective cohort, hospital-based medical database

The infiltration of cytotoxic T lymphocytes holds promise for suppressing even the most resilient metastatic tumors in immunotherapy. Polarizing tumor-associated macrophages (TAMs) and remodeling the immune-deficient tumor microenvironment (TME) can enhance T lymphocyte recruitment and infiltration. However, the immune privilege and low immunogenic responses of these aggressive tumor clusters often limit lymphocyte recruitment. Here, an M1 macrophage membrane-coated iron oxide nanoparticle (IO@MM) double as a tumor-penetrated agent and naïve M0 macrophage to M1 polarizer is developed for lung metastatic colorectal cancer (CRC) immunotherapy. At the tumor site, IO@MM combined with resiquimod (R848) increased the immune cell infiltration, turning the "Cold" TME into an immune-activating "Hot" one. Together with self-cascade immunotherapy, IO@MM with R848 promotes tumor release of damage-associated molecular patterns (DAMPs). At the same time, IO@MM uses the membrane as an antigen reservoir and provides autologous DAMPs to retain dendritic cells. This IO@MM effectively inhibits tumors and improves survival rate as an immunomodulator in lung metastasis., (© 2024 Wiley‐VCH GmbH.)

Progress toward single-molecule electronics relies on a thorough understanding of local physico-chemical processes and development of synthetic routines for controlled hetero-coupling. We demonstrate a structurally unexpected ring closure process for a homo-coupled 4,4'-bipicenyl, realized in on-surface synthesis. An initial covalent C-C coupling of 4-bromopicene locks at lower temperatures the position and geometrically shields part of 4,4'-bipicenyl. Employing this effect of shielding might offer a path toward controlled stepwise hetero-coupling. At higher temperatures, a thermally activated three-dimensional rotation upon hydrogen dissociation, a dehydrogenative roto-cyclization, lifts the surface-dimensionality restriction, and leads to the formation of a perylene. Thereby, the shielded molecular part becomes accessible again., (© 2024 Wiley-VCH GmbH.)

This study aimed to determine the associations of childhood exposure to bisphenol A (BPA) and parabens (PBs) with oxidative stress and the activity of outer hair cells (OHCs) in the cochlea of children with hearing loss (HL). A total of 641 children were enrolled in this cross-sectional study. Urinary concentrations of BPA and four PBs including methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), and butyl paraben (BP) were quantified by using liquid chromatography-tandem mass spectrometry (LC/MSMS). Four urinary biomarkers of oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO 2 Gua), 4-hydroxynonenal mercapturic acid (HNE-MA), and 8-isoprostaglandin F2α (8-iso-PGF 2α ), were measured using high-performance liquid chromatography-electrospray ionization mass spectrometry. Hearing tests were conducted by an audiologist in the audiometric test room, and the results were confirmed by an otolaryngologist. The activity of OHCs in the cochlea was measured by distortion product otoacoustic emissions (DPOAEs). The associations of BPA/PB exposure and oxidative stress with the activity of OHCs at different frequencies were evaluated in the multivariable linear regression models. There were 91 children with HL, for an incidence of approximately 14.2 %. There was a significant negative association between the presence of EP (1.5 K Hz, 3 K Hz) or PP (2 K Hz) or 8-OHdG (1 K Hz, 1.5 K Hz, 2 K Hz) and the activity of OHCs in the left ear. Significant results were also observed for BPA (2 K Hz), MP (1 K Hz, 1.5 K Hz, 2 K Hz), EP (3 K Hz), and 8-OHdG (2 K Hz) in the right ear. This study revealed that exposure to BPA/PBs reduces the activity of OHCs, especially at middle frequencies, in children., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

The concentration of PM 2.5 (particulate matter with a diameter < 2.5 µm) on Sumatra Island has increased, mainly because of forest and peatland fires, transportation, and industry. Biomass burning releases partially burned carbon into the atmosphere, resulting in a smoky haze containing PM 2.5 . Air quality has deteriorated quickly, and PM 2.5 has become a major health hazard in Indonesia. Studies on long-term exposure to PM 2.5 have indicated its associations with both morbidity and mortality. Here, we measured long-term (2000-2014) exposure to PM 2.5 on the basis of satellite-derived aerosol optical depth measurements (1 × 1 km 2 ) used to predict ground-level PM 2.5 concentrations. Additionally, population data on Sumatra Island residents from the fourth wave of the Indonesian Family Life Survey (IFLS) were obtained. We investigated the association between long-term PM 2.5 exposure and mortality with a retrospective cohort study design. A total of 2409 subjects aged ≥ 40 years participated in the IFLS-3 beginning in November 2000, and we examined mortality outcomes until the IFLS-5 in September 2014. We used Cox regression models to calculate hazard ratios (HRs) of mortality associated with PM 2.5 exposure. According to the adjusted model, the mortality HRs per 10 µg/m 3 increase in PM 2.5 concentration were 1.10 (95% CI 1.03, 1.17) for all natural causes, 1.17 (95% CI 1.05, 1.25) for cardiovascular causes, and 1.19 (95% CI 1.04, 1.36) for respiratory causes. Long-term exposure to PM 2.5 was associated with all-natural, cardiovascular, and respiratory mortality on Sumatra Island, where PM 2.5 levels exceed the WHO and US-EPA air quality standards., (© 2024. The Author(s).)

Background: Air pollution is recognized as a modifiable risk factor for dementia, and recent evidence suggests that improving air quality could attenuate cognitive decline and reduce dementia risk. However, studies have yet to explore the effects of improved air quality on brain structures. This study aims to investigate the impact of air pollution reduction on cognitive functions and structural brain differences among cognitively normal older adults., Methods: Four hundred and thirty-one cognitively normal older adults were from the Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT), a community-based cohort of adults aged 60 and older, between year 2017- 2021. Annual concentrations of PM 2.5 , NO 2 , O 3 , and PM 10 at participants' residential addresses during the 10 years before enrollment were estimated using ensemble mixed spatial models. The yearly rate of change (slope) in air pollutants was estimated for each participant. Cognitive functions and structural brain images were collected during enrollment. The relationships between the rate of air pollution change and cognitive functions were examined using linear regression models. For air pollutants with significant findings in relation to cognitive function, we further explored the association with brain structure., Results: Overall, all pollutant concentrations, except O 3 , decreased over the 10-year period. The yearly rates of change (slopes) in PM 2.5 and NO 2 were correlated with better attention (PM 2.5 : r = -0.1, p = 0.047; NO 2 : r = -0.1, p = 0.03) and higher white matter integrity in several brain regions. These regions included anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, and inferior fronto-occipital fasciculus., Conclusions: Greater rate of reduction in air pollution was associated with better attention and attention-related white matter integrity. These results provide insight into the mechanism underlying the relationship between air pollution, brain health, and cognitive aging among older adults., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Replacement of sp 2 -hybridized carbon in polycyclic aromatic hydrocarbons (PAHs) by boron affords electron-deficient π-scaffolds due to the vacant p z -orbital of three-coordinate boron with the potential for pronounced electronic interactions with electron-rich metal surfaces. Using a diboraperylene diborinic acid derivative as precursor and a controlled on-surface non-covalent synthesis approach, we report on a self-assembled chiral supramolecular kagome network on an Ag(111) surface stabilized by intermolecular hydrogen-bonding interactions at low temperature. Scanning tunneling microscopy (STM) and spectroscopy (STS) reveal a flat band at ca. 0.33 eV above the Fermi level which is localized at the molecule center, in good agreement with tight-binding model calculations of flat bands characteristic for kagome lattices., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The study aimed to evaluate the impact of occupational noise on hearing loss among healthcare workers using audiometry. A longitudinal study was conducted with a six-month follow-up period in a hospital with 21 participants, divided into high-noise-exposure (HNE) and low-noise-exposure (LNE) groups. Mean noise levels were higher in the HNE group (70.4 ± 4.5 dBA), and hearing loss was measured using pure-tone audiometry at baseline and follow-up. The HNE group had significantly higher mean threshold levels at frequencies of 0.25 kHz, 0.5 kHz, 4.0 kHz, and an average of 0.5, 1, 2, and 4 kHz (all p-values < 0.05) after the follow-up period. After adjusting for confounding factors, the HNE group had significantly higher hearing loss levels at 0.25 kHz, 0.5 kHz, and average frequencies of 0.5, 1, 2, and 4 kHz compared to the LNE group at the second measurement. Occupational noise levels above 65 dBA over six months were found to cause significant threshold changes at frequencies of 0.25 kHz, 0.5 kHz, and an average of 0.5-4.0 kHz. This study highlights the risk of noise-induced hearing loss among healthcare workers and emphasizes the importance of implementing effective hearing conservation programs in the workplace. Regular monitoring and assessment of noise levels and hearing ability, along with proper use of personal protective equipment, are crucial steps in mitigating the impact of occupational noise exposure on the hearing health of healthcare workers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid - related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate - nitrite - nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD)., Methods: We conducted a retrospective hospital - based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2 - receptor antagonists ( H2RAs ) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on - treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity - score - matching. Sub - group analysis, multi - bias E - values, and array - based sensitivity analysis for some covariates were used to assess the robustness of associations., Results: A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score - matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders ( i.e. , smoking and alcohol)., Conclusion: PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders., Competing Interests: The authors declare that they have no competing interests., (© 2024 Pannoi et al.)

Background: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM 2.5 ) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer., Objective: To evaluate the association of long-term exposure to metal constituents in PM 2.5 with the risk of liver cancer using a Taiwanese cohort study., Methods: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991-1992. Participants' long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM 2.5 was based on ambient measurement in 2002-2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991-2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM 2.5 metal component and HCC., Results: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM 2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02-1.25; P = 0.023) with one unit increment on Cu normalized by PM 2.5 mass concentration in the logarithmic scale. The PM 2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM 2.5 ., Conclusion: Our findings suggest PM 2.5 containing Cu may attribute to the association of PM 2.5 exposure with liver cancer.

Background: Exposure to greenness has been shown to be beneficial to health, but few studies have examined the association between residential greenness and prostate cancer (PCa) risk. Our main objectives were to identify the determinants of residential greenness, and to investigate if residential greenness was associated with PCa risk in Singapore., Methods: The hospital-based case-control study was conducted between April 2007 and May 2009. The Singapore Prostate Cancer Study (SPCS) comprised 240 prostate cancer cases and 268 controls, whose demographics and residential address were collected using questionnaires. Residential greenness was measured by normalized difference vegetation index (NDVI) around the participants' homes using a buffer size of 1 km. Determinants of NDVI were identified using a multivariable linear regression model. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of associations between NDVI and PCa risk, adjusting for potential confounders., Results: Having a BMI within the second quartile, as compared to the lowest quartile, was associated with higher levels of NDVI (β-coefficient = 0.263; 95% CI = 0.040-0.485) after adjusting for covariates. Additionally, being widowed or separated, as compared to being married, was associated with lower levels of NDVI (β-coefficient = -0.393; 95% CI = -0.723, -0.063). An interquartile range (IQR) increase in NDVI was positively associated with prostate cancer risk OR = 1.45; 95% CI = 1.02-2.07). Stratified analysis by tumour grade and stage showed that higher NDVI was associated with higher risk of low grade PCa., Conclusion: Our findings suggested that residential greenness was associated with higher risk of PCa in Singapore. Future studies on the quality and type of green spaces, as well as other factors of residential greenness, in association with PCa risk should be conducted to better understand this relationship., 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. Published by Elsevier Inc.)

It is generally established that PCDD/Fs is harmful to human health and therefore extensive field research is necessary. This study is the first to use a novel geospatial-artificial intelligence (Geo-AI) based ensemble mixed spatial model (EMSM) that integrates multiple machine learning algorithms and geographic predictor variables selected using SHapley Additive exPlanations (SHAP) values to predict spatial-temporal fluctuations in PCDD/Fs concentrations across the entire island of Taiwan. Daily PCDD/F I-TEQ levels from 2006 to 2016 were used for model construction, while external data was used for validating model dependability. We utilized Geo-AI, incorporating kriging, five machine learning, and ensemble methods (combinations of the aforementioned five models) to develop EMSMs. The EMSMs were used to estimate long-term spatiotemporal variations in PCDD/F I-TEQ levels, considering in-situ measurements, meteorological factors, geospatial predictors, social and seasonal influences over a 10-year period. The findings demonstrated that the EMSM was superior to all other models, with an increase in explanatory power reaching 87 %. The results of spatial-temporal resolution show that the temporal fluctuation of PCDD/F concentrations can be a result of weather circumstances, while geographical variance can be the result of urbanization and industrialization. These results provide accurate estimates that support pollution control measures and epidemiological studies., 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.)

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P&lt;0.01), increased lipid accumulation in the liver(P&lt;0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P&lt;0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P&lt;0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P&lt;0.05, P&lt;0.01), reduced lipid accumulation in the liver(P&lt;0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P&lt;0.05, P&lt;0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P&lt;0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Seven previously undescribed meroterpenoids, peniscmeroterpenoids H - N (1-7), were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid H was a 6/6/6/5/6 rearranged pentacyclic meroterpenoid, featuring a unique 2-oxaspiro[5.5] undeca-4,7-dien-3-one motif. Peniscmeroterpenoids I and J (2 and 3) owned rare 6(D)/5(E) fused rings were not common in natural products, and compound 2 was the second example of a berkeleyone analogue stripped of the methyl ester fragment. Peniscmeroterpenoid K (4) was the first case where the C-24 was oxidized. In bioassay, compound 5 showed moderate anti-inflammatory activity., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Both greenness and air pollution have widely been linked with asthma. However, the potential mechanism has rarely been investigated. This study aimed to identify the association between residential greenness and air pollution (fine particulate matter [PM 2.5 ]; nitrogen dioxide [NO 2 ]; ozone [O 3 ]) with nasal microbiota among asthmatic children during the recovery phase. The normalized difference vegetation index was used to assess the extent of residential greenness. Spatiotemporal air pollution variation was estimated using an integrated hybrid kriging-LUR with the XG-Boost algorithm. These exposures were measured in 250-m intervals for four incremental buffer ranges. Nasal microbiota was collected from 47 children during the recovery phase. A generalized additive model controlled for various covariates was applied to evaluate the exposure-outcome association. The lag-time effect of greenness and air pollution related to the nasal microbiota also was examined. A significant negative association was observed between short-term exposure to air pollution and nasal bacterial diversity, as a one-unit increment in PM 2.5 or O 3 significantly decreased the observed species (PM 2.5 : -0.59, 95%CI -1.13, -0.05 and O 3 : -0.93, 95%CI -1.54, -0.32) and species richness (PM 2.5 : -0.64, 95%CI -1.25, -0.02 and O 3 : -0.68, 95%CI -1.43, -0.07). Considering the lag-time effect, we found a significant positive association between greenness and both the observed species and species richness. In addition, we identified a significant negative association for all pollutants with the observed species richness. These findings add to the evidence base of the links between nasal microbiota and air pollution and greenness. This study establishes a foundation for future studies of how environmental exposure plays a role in nasal microbiota, which in turn may affect the development of asthma., 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 Inc. All rights reserved.)

Four new chromone compounds diaporspchromanones A-C (1-3) and diaporspchromanone H (4), together with three known compounds (5-7) were separated from the marine derived fungus Diaporthe sp. XW12-1. The structures of the new compounds, including their absolute configurations, were elucidated by extensive spectroscopic analysis and the Mosher's ester method. Among them, diaporspchromanones A-C (1-3) possess a 3-substituted-chroman-4-one skeleton, which are rarely found in natural sources. In the bioassays, all compounds were evaluated for their inhibitory activity against lipopolysaccharide-activated nitric oxide (NO) production in RAW264.7 cells. Compounds 2 and 3 showed potent anti-inflammatory effects than the positive control (indomethacin, IC 50 , 70.33 ± 0.95 μM) (p < 0.05) with IC 50 values of 19.06 ± 3.60 and 9.56 ± 0.18 μM, respectively., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2022. Published by Elsevier B.V.)

Seven undescribed meroterpenoids, peniscmeroterpenoids A - G, were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid A possessed an unprecedented and highly oxidized 6/7/6/5/5 pentacyclic system, featuring a unique tetrahydrofuro [2,3-b]furan-2(3H)-one motif. Peniscmeroterpenoids B - E owned rare 6(D)/5(E) fused rings were not common in natural products, and peniscmeroterpenoid E is the first example of a berkeleyone analogue stripped of the methyl ester fragment. In bioassays, peniscmeroterpenoids A and D inhibited the production of nitric oxide (NO) in RAW264.7 cells with IC 50 values of 26.60 ± 1.15 and 8.79 ± 1.22 μM. Moreover, peniscmeroterpenoid D significantly suppressed the production of pro-inflammatory mediators (COX-2, IL-1β and IL-6) and the protein expression of the enzyme iNOS., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., 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 Asri, Tsai, Wong, Lee, Pan, Guo, Wu, Su, Wu and Spengler.)

Prenatal perfluoroalkyl substance (PFAS) exposure has been linked to adverse birth outcomes, but the underlying mechanism has yet to be elucidated. DNA methylation changes in mesoderm-specific transcript (MEST) imprinted gene may be a mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim was to investigate the prenatal PFASs exposure effects on DNA methylation changes in MEST imprinted gene involved in fetal growth. Among 486 mother-infant pairs from the Taiwan Birth Panel Study, PFASs and DNA methylation levels at 5 CpG sites of MEST promoter region were measured in cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFAS exposure, MEST DNA methylation levels, and child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation between PFASs and birth outcomes. We found that higher prenatal perfluorooctyl sulfonate (PFOS) exposure was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region (an adjusted β range: -1.56, -2.22). Significant negative associations were also found between MEST methylation levels and child birth weight. Furthermore, the associations between PFOS and perfluorooctanoic acid (PFOA) exposure and MEST methylation levels were more profound in girls than in boys. The mediated effect of average MEST methylation level between PFOS exposure and birth weight was 18.3 (95% CI = 2.1, 40.2; p = 0.014). The direct effect of PFOS exposure to birth weight independent to average MEST methylation level was -93.2 (95% CI = -170.5, -17.8; p = 0.018). In conclusion, our results suggest that prenatal PFAS exposure, especially PFOS, is associated with lower methylation levels at MEST promoter region, which not only leverages the role of imprinted gene in ensuring the integrity of fetal growth but also provides a potential mechanism for evaluating the prenatal exposure effect., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., 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 Asri, Tsai, Pan, Guo, Yu, Wu, Su, Lung, Wu and Spengler.)

Exposure to particulate matter with a diameter < 2.5 µm (PM 2.5 ) increases the risk of cardiovascular disease (CVD), which is the leading cause of both morbidity and mortality in Indonesia, accounting for one-third of all deaths. Indonesian authorities started to monitor PM 2.5 levels in urban areas in 2015. However, there is still no study examining the association between long-term PM 2.5 exposure and CVD in Indonesia. In this study, we combined PM 2.5 data and health survey data. Long-term (2000-2007) exposure to PM 2.5 was measured based on satellite-derived aerosol optical depth measurements (1 × 1 km 2 ) that could be used to predict ground-level PM 2.5 concentrations. Population data on residents of Sumatra Island were obtained from the fourth wave of the Indonesian Family Life Survey (IFLS). A cross-sectional study was performed with 2324 participants who were aged ≥ 40 years old, and a report of doctor-diagnosed CVD determined CVD status. We used logistic regression to analyze the association between PM 2.5 and CVD prevalence, adjusting for multiple covariates. Of the sample, 52.1% were women, and 47.9% were men. The sample was divided into those aged 40-59 (adults) and those ≥ 60 (older adults). The CVD prevalence was 4.05% (n = 94), with a mean (standard deviation) PM 2.5 concentration of 14.4 (6.4) µg/m 3 . In adjusted models, a 10-µg/m 3 increase in annual average PM 2.5 levels was associated with 29% higher odds of having CVD (odds ratio = 1.29; 95% confidence interval: 1.02, 1.47). In this population-based IFLS data, long-term exposure to PM 2.5 is associated with a higher prevalence of CVD in Sumatera, Indonesia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The proportion of allergic diseases attributable to atopy remains a subject of controversy. This study aimed to estimate the population risk of physician-diagnosed asthma, rhinitis and eczema attributed to atopy among a population sample of Asian school-age children. Asian children aged 5-18 years (n = 1321) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were tested for serum allergen-specific immunoglobulin E. Physician-diagnosed asthma, rhinitis and eczema were assessed by a modified International Study of Asthma and Allergies in Childhood questionnaire. Atopy was defined as the presence of serum allergen-specific immunoglobulin E. In this population-based study, 50.4% of the subjects with asthma, 46.3% with rhinitis, and 46.7% with eczema were attributable to atopy. The population attributable risk (PAR) of atopy for three allergic diseases was higher in adolescents (asthma, 54.4%; rhinitis, 59.6%; eczema, 49.5%) than younger children aged less than 10 years (asthma, 46.9%; rhinitis, 39.5%; eczema, 41.9%). Among the seven allergen categories, sensitization to mites had the highest PARs for all three allergic diseases (51.3 to 64.1%), followed by sensitization to foods (asthma, 7.1%; rhinitis, 10.4%; eczema 27.7%). In conclusion, approximately half (46.3 to 50.4%) of Asian children in Taiwan with allergic diseases are attributable to atopy., (© 2021. The Author(s).)

Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J - L (5-7), linderaguaianols A and B (8 and 9), together with six known ones 10-15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo 2 (AcO) 4 -induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1-4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC 50 value of 1.73 ± 0.18 μM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses., (Copyright © 2021. Published by Elsevier Inc.)

Background: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality., Methods: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000-2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005-2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM 2.5 was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM 2.5 on the relationship between traffic and CVD mortality., Results: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94-1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03-1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM 2.5 had an over 60% mediation effect on traffic-CVD association., Conclusions: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.

This study aimed to identify the spatial patterns of lower respiratory tract infections (LRIs) and their association with fine particulate matter (PM 2.5 ). The disability-adjusted life year (DALY) database was used to represent the burden each country experiences as a result of LRIs. PM 2.5 data obtained from the Atmosphere Composition Analysis Group was assessed as the source for main exposure. Global Moran's I and Getis-Ord Gi* were applied to identify the spatial patterns and for hotspots analysis of LRIs. A generalized linear mixed model was coupled with a sensitivity test after controlling for covariates to estimate the association between LRIs and PM 2.5 . Subgroup analyses were performed to determine whether LRIs and PM 2.5 are correlated for various ages and geographic regions. A significant spatial auto-correlated pattern was identified for global LRIs with Moran's Index 0.79, and the hotspots of LRIs were clustered in 35 African and 4 Eastern Mediterranean countries. A consistent significant positive association between LRIs and PM 2.5 with a coefficient of 0.21 (95% CI 0.06-0.36) was identified. Furthermore, subgroup analysis revealed a significant effect of PM 2.5 on LRI for children (0-14 years) and the elderly (≥ 70 years), and this effect was confirmed to be significant in all regions except for those comprised of Eastern Mediterranean countries.

Background: To date, there is no comprehensive study examining how asthma diagnosed in childhood or adolescence is associated with diagnoses of subsequent non-communicable diseases (NCDs) during adulthood. Our study aimed to examine the associations between pediatric asthma and several adult NCDs, with temporality and long interval times between asthma and NCD diagnoses., Methods: We used RAND Indonesian Family Life Survey Fifth Wave (IFLS5) fielded in 2014-2015, to study whether being diagnosed with pediatric asthma at 0-19 years of age was associated with increased risks of hypertension, diabetes, rheumatoid arthritis, stomach diseases, kidney diseases, and heart diseases or stroke diagnosed in adulthood. We used the weighted Poisson regression adjusting for age, sex, urbanicity, and insurance status to estimate risk ratios. Subgroup analyses were performed by sex and age of asthma and other NCD diagnoses., Results: Pediatric asthma significantly increased risks of hypertension, diabetes, and stomach diseases diagnosed at 20 years of age or above. Males with pediatric asthma diagnosed at 0-10 years of age had significantly higher risk of hypertension, while females with pediatric asthma diagnosed at 0-10 years of age had significantly higher risks of diabetes and stomach diseases. Females with pediatric asthma diagnosed at 11-19 years of age had significantly higher risks of diabetes, arthritis, stomach diseases, and kidney diseases. We also found varying associations by age of NCD diagnosis., Conclusion: Our results suggest pediatric asthma is associated with increased risks of several adult NCDs, and these associations may vary by sex and age of asthma and other NCD diagnoses., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

This study determines whether surrounding greenness is associated with the incidence of type 2 diabetes Mellitus (T2DM) in Taiwan. A retrospective cohort study determines the relationship between surrounding greenness and the incidence of T2DM during the study period of 2001-2012 using data from the National Health Insurance Research Database. The satellite-derived normalized difference vegetation index (NDVI) from the global MODIS database in the NASA Earth Observing System is used to assess greenness. Cox proportional hazard models are used to determine the relationship between exposure to surrounding greenness and the incidence of T2DM, with adjustment for potential confounders. A total of 429,504 subjects, including 40,479 subjects who developed T2DM, were identified during the study period. There is an inverse relationship between exposure to surrounding greenness and the incidence of T2DM after adjustment for individual-level covariates, comorbidities, and the region-level covariates (adjusted HR = 0.81, 95% CI: 0.79-0.82). For the general population of Taiwan, greater exposure to surrounding greenness is associated with a lower incidence of T2DM., Competing Interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Scope: Coffee and tea are among the most popular beverages in the world. However, the association between habitual coffee, green tea, and black tea consumption with metabolomics profiles in Asian populations remain largely unknown., Methods and Results: 158 metabolites (14 amino acids, 45 acylcarnitines, and 99 sphingolipids) in the blood plasma of participants are measured from the population-based Singapore Prospective Study Program cohort using mass spectrometry (MS). Linear regression models are used to obtain the estimates for the association between coffee and tea consumption with metabolite levels, adjusted for potential confounders and false discovery rate (FDR). Coffee consumption is significantly associated with higher levels of 63 sphingolipids (29 sphingomyelins, 32 ceramides, a sphingosine-1-phosphate, and a sphingosine) and lower levels of 13 acylcarnitines and alanine. Black tea consumption is significantly associated with higher levels of eight sphingolipids, and lower levels of an amino acid, whereas green tea is significantly inversely associated with four metabolites (C8:1-OH acylcarnitine, ganglioside GM3 d18:1/16:0, sphingomyelins d18:2/18:0 and d18:1/14:0)., Conclusions: Coffee, black tea, and green tea consumption are associated with plasma levels of certain classes of sphingolipids and acylcarnitines in an Asian population, particularly sphingomyelins, which may mediate the health benefits of these beverages., (© 2020 Wiley-VCH GmbH.)

Atmospheric polychlorinated-dibenzo-dioxins/dibenzo-furans (PCDD/Fs) remains an important environmental health concern. Although the total emission inventories of PCDD/Fs in Taiwan decreased from 320 to 52.1 g-I-TEQ/year during 2002-2016, the resulting concentrations of atmospheric PCDD/F and distributions in Taiwan are unknown. We, therefore, conducted a comprehensive investigation of spatial and seasonal variations and apportioned potential sources of ambient PCDD/F concentrations in Taiwan-based on 11-year observation data. A total of 1,008 atmospheric PCDD/F samples were collected from 25 air monitoring stations (from seven areas) and 1 background station for 2006-2016. Linear regression was used to model changes in PCDD/F concentrations. Principal component analysis (PCA) and positive matrix factorization (PMF) were used to identify potential contributors. PCDD/F concentrations in the ambient air gradually decreased during the study period, with a median concentration of 28.2 fg I-TEQ/m3 over 11 years. The highest median PCDD/F concentrations were found in the highly industrialized regions of western Taiwan (38.0-43.4 fg I-TEQ/m3). Lower concentrations were found in eastern Taiwan (∼10 fg I-TEQ/m3). Background stations reported the lowest concentrations of PCDD/Fs, with a median concentration of 1.47 fg I-TEQ/m3. Overall, the concentrations of atmospheric PCDD/Fs in Taiwan were higher in winter (13.4-86.7 fg I-TEQ/m3) than in summer (9.65-27.2 fg I-TEQ/m3). The PCA results indicated that PCDD/F profiles varied by both region (industrialized, urbanized, and background areas) and season. The PMF model for the overall data revealed that the major sources of PCDD/Fs were industrial activities (71.2%). However, in less industrialized areas, traffic activities, long-range transport, and open burning were dominant., 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.)

The rising prevalence and incidence of end-stage renal disease (ESRD) have been noted around the world. However, no study has been conducted to examine the effect of surrounding environment on incidence of ESRD. This study assessed the associations of exposure to PM2.5 level and surrounding green spaces, separately, with incidence of ESRD in Taiwan. Demographic and clinical data used in this study was retrieved from the National Health Insurance Research Database from 2003 to 2012. PM2.5 data collected from the Environmental Protection Administration of Taiwan and a hybrid land-use regression model was used to approximate long-term exposure to PM2.5. Percentage of exposure to surrounding green spaces was used to determine individual exposure level. Cox proportional hazards models with a generalized estimating equation were applied to investigate the effect of surrounding environment on incidence of ESRD. The results showed significant positive association between exposure to PM2.5 level and incidence of ESRD; but inverse association between exposure to surrounding green spaces and incidence of ESRD (adjusted hazard ratio (AHR) = 1.08, 95% CI: 1.00-1.15 for exposure to PM2.5 level; AHR = 0.90, 95%CI: 0.84-0.98 for surrounding green spaces). Together, the findings from this study have added suggestive evidence on the adverse effect of exposure to PM2.5 level and the beneficial effect of exposure to surrounding green spaces on the incidence of ESRD in a general population in Taiwan., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Exposure to surrounding greenness is associated with reduced mortality in Caucasian populations. Little is known however about the relationship between green vegetation and the risk of death in Asian populations. Therefore, we opted to evaluate the association of greenness with mortality in Taiwan. Death information was retrieved from the Taiwan Death Certificate database between 2006 to 2014 (3287 days). Exposure to green vegetation was based on the normalized difference vegetation index (NDVI) collected by the Moderate Resolution Imagine Spectroradiometer (MODIS). A generalized additive mixed model was utilized to assess the association between NDVI exposure and mortality. A total of 1,173,773 deaths were identified from 2006 to 2014. We found one unit increment on NDVI was associated with a reduced mortality due to all-cause (risk ratio [RR] = 0.901; 95% confidence interval = 0.862-0.941), cardiovascular diseases (RR = 0.892; 95% CI = 0.817-0.975), respiratory diseases (RR = 0.721; 95% CI = 0.632-0.824), and lung cancer (RR = 0.871; 95% CI = 0.735-1.032). Using the green land cover as the alternative green index showed the protective relationship on all-cause mortality. Exposure to surrounding greenness was negatively associated with mortality in Taiwan. Further research is needed to uncover the underlying mechanism.

Metabolic syndrome is becoming more common worldwide. Studies suggest environmental pollution, including traffic noise, might be linked with metabolic syndrome. This study sought to evaluate how noise exposure is linked to the development of metabolic syndrome and its components in Taiwan. Using data from a cohort of 42,509 participants and Cox proportional hazards regression models, the effects of noise exposure on metabolic syndrome and its components were quantified. After adjustment for covariates (age, gender, body mass index, and physical activity), the hazard ratio for metabolic syndrome was 1.13 (95% CI: 1.04-1.22) for medium noise exposure and 1.24 (95% CI: 1.13-1.36) for high noise exposure. Noise exposure was also positively associated with all of metabolic syndrome's components. This finding suggests noise exposure might contribute to metabolic syndrome and its components. Policies aiming to reduce noise pollution might reduce the risks of metabolic syndrome and its components.

Exposure to fine particulate matter (PM 2.5 ) is associated with cardiovascular disease risk. To date, there are few studies on short-term PM 2.5 exposure in different microenvironments and its impact on immediate health effects, particularly in the Southeast Asia region. This study assessed PM 2.5 concentrations in different microenvironments in a densely populated city in the tropics using low-cost personal PM 2.5 sensors as well as their associations with acute cardiovascular health outcomes. A total of 49 adult participants affiliated with the National University of Singapore (NUS) community were recruited. Personal low-cost sensors were used to measure PM 2.5 concentrations between September 2017 and March 2019. Demographic information and time-activity patterns were collected using questionnaires. Wilcoxon pairwise comparisons were used to determine statistical differences between PM 2.5 exposures at 18 different microenvironments. Generalized Estimating Equations (GEE) models were used to assess the association between PM 2.5 exposure and blood pressure as well as heart rate. All models were adjusted for age, sex, body mass index, physical activity, temperature, duration of exposure, and baseline cardiovascular parameters. Significant differences in PM 2.5 concentrations were observed across different microenvironments. Air-conditioned offices and tertiary teaching spaces had the lowest (median = 13.1 μg/m 3 ) and hawker centres had the highest (median = 32.0 μg/m 3 ) PM 2.5 concentrations. Significant positive associations between PM 2.5 exposure and heart rate (β = 0.40, p = 4.6 × 10 -5 ) as well as diastolic blood pressure (β = 0.16, p = 0.0077) were also observed. Short-term exposure to PM 2.5 was significantly associated with higher heart rate and blood pressure. Further work is needed to investigate the variations within each type of microenvironment and expand the study to other sub-populations such as the elderly and children., 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 Elsevier B.V. All rights reserved.)

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this paper, perovskite-type SrTiO 3 nanocubes decorated reduced graphene oxide is synthesized by sonochemical method. The as-synthesized SrTiO 3 @RGO nanocomposite was confirmed by XRD, TEM, SEM, elemental mapping and electrochemical technique. Furthermore, surface morphological and X-ray diffraction studies revealed the formation and high loading of SrTiO 3 nanocubes on reduced graphene oxide matrix. The SrTiO 3 @RGO nanocomposite modified electrode shows an excellent electrochemical detection towards of amino acid (tryptophan). The developed sensor was showed a wide linear range from 30 nM to 917.3 µM and detection limit is 7.15 nM. Furthermore, the sensitivity was calculated to be 9.11 µA µM -1  cm 2 . In addition, the proposed modified sensor is exhibited good selectivity, stability, reproducibility and repeatability. The SrTiO 3 @RGO catalyst modified electrode was successfully applied to tryptophan analysis in biological samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: We evaluated the relationship between the age at first use of oral contraceptives (OC) and breast cancer (BC) risk., Methods: We searched PubMed, Embase, and related reviews published through June 28, 2018, and used summary relative risk (RR) and 95% confidence intervals (CIs) to evaluate the cancer risks, and fixed-effects dose-response meta-analysis to assess potential linear and non-linear dose-response relationships., Results: We included 10 studies, with 8585 BC cases among 686,305 participants. The pooled RR for BC was 1.24 (95% CI: 1.10-1.41), with moderate heterogeneities (I = 66.5%, P < .001). No significant publication bias was found (P = .584 for Begg test, P = .597 for Egger test). A linear dose-response relationship between the age at first OC use and BC risk was detected (P = .518 for non-linearity). Subgroup analyses were restricted to studies done by BC subtypes, region, sample size, follow-up time and study quality. Inconsistent consequences with no statistical significance were explored when limited to studies from Western countries, study quality <7, sample size <10,000, follow-up time <5 years, and BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expression status in tumor tissue. Sensitivity analyses indicated that our results were stable and reliable after removing each study in turn and omitting studies of adjusted unreported variables., Conclusion: A significant linear relationship between the age at first OC use and BC risk was confirmed. No further consistent differences are noted in multiple aspects of BC subtypes defined by progesterone or ER status.

Parabens are a group of esters of parahydroxybenzoic acid and are utilized as antimicrobial preservatives in the majority of personal care products (PCPs). Epidemiological studies regarding the adverse effects of parabens on fetuses are still limited. The aim of this study was to determine the association between maternal paraben exposure and birth outcomes. One hundred and ninety-nine pregnant women were enrolled, and maternal urine was collected in the third trimester. The urine concentrations of four parabens (methyl (MP), ethyl (EP), propyl (PP), and butyl (BP)) were determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the association between paraben exposure levels and birth outcomes. A causal mediation analysis was conducted to determine the mediation effect of oxidative stress on birth outcomes. The geometric means of urinary MP, EP, PP, and BP were 51.79, 1.26, 4.21, and 1.25 μg/g cre., respectively. In the penalized regression splines, sex-specific associations between maternal MP levels and birth outcomes were observed; a downward curvature was observed between the MP level and birth weight, length, head circumference, and thoracic circumference among female newborns. Pregnant women in the group with MP levels above the third quartile had neonates with significantly lower body weight (β = -215.98 g, p value = 0.02) compared to those in the group with MP levels lower than the third quartile. No significant mediation of oxidative stress was observed between maternal MP exposure and female birth weight. The estimated proportion mediated ranged from -6% to 15%. The negative association between maternal paraben exposure and female birth outcomes in relation to child development should be carefully considered., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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.

Background: We aimed to examine the effect of ambient air pollution at the district level on adolescents' happiness and their change in happiness over time in a cohort sample from Taiwan., Method: A cohort from the Taiwan Youth Project was evaluated. The adolescents (n = 2571) were in the 7th grade (mean age = 14.3 years) when the study was initiated and resided in 40 districts in three cities and counties in northern Taiwan. We examined the effects of the concentration level of air pollution, including PM 2.5 , PM 10 , and NO 2 , at the district level on adolescents' happiness and their change in happiness over time (7th to 9th grade). Due to the high correlations of the three pollutants, we examined each separately with similar covariates. The analyses were based on both multilevel modeling and latent growth curve modeling., Results: Higher concentration levels of each of the three air pollutants measured were associated with adolescent happiness such that a higher level of concentration was related to lower levels of adolescents' happiness. These results were observed after controlling for important individual- and district-level covariates. However, further analyses did not reveal that the concentration level of air pollution was associated with the change in happiness in the study period (after 3 years). Some sensitivity checks (e.g., adjusting district size) did not change the substantive results., Conclusion: Many previous studies have shown the influence of air pollution on physical health and negative emotions, but only a few using adult samples have shown that air pollution is inversely related to positive wellbeing. This study may be the first to examine the effects of air pollution on adolescents' positive affect. Our results echo recent research on the consequent health burden of air pollution. Given that positive affect has been linked to future adult health, the results of the current study provide empirical grounds for early intervention concerning environmental factors.

This study aims to investigate the association between surrounding greenness and schizophrenia incidence in Taiwan. Data of 869,484 individuals without a history of schizophrenia were included from the Longitudinal Health Insurance Database from 2000 through 2010 for analysis. The diagnoses of schizophrenia were based on ICD-9 codes. Greenness exposure was assessed using the satellite-based normalized difference vegetation index, assuming individuals lived near the hospital they most often visited for common cold during the study period. Cox proportional hazards models were applied to assess the association between greenness exposure and schizophrenia incidence after adjustments were made for the potential confounders. A total of 5,069 schizophrenia cases were newly diagnosed during the study period. A negative significant (P < 0.05) association found using 2,000-m buffer distances (distance of a moderately paced 20-min walk) in the whole Taiwan island, cities, and metropolitan areas. The results of the stratified analysis based on sex and health insurance rate suggested surrounding greenness has approximately equal effects of reducing the risk of schizophrenia, regardless of sex or financial status. In conclusion, our findings suggest that more surrounding greenness may reduce the risk of schizophrenia., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

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.

Dioxane was found to be involved in the reaction of 2-(arylethynyl)benzaldehydes and 3-aminopyrazine-2-carbohydrazide, and underwent a ring-opening reaction catalyzed by AgOTf. This domino type procedure provided an efficient method for the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields via the loss of a molecule of 3-aminopyrazine-2-carboxamide.

Previous studies have confirmed that activity participation is beneficial to mental health, but few studies focus on older adults' depression. Based on the theory of social integration, this study examined the effects of leisure activity diversity and exercise time on depression in late adulthood. Subjects in the 2011 Survey of Health and Living Status of the Middle-Aged and Elderly in Taiwan were extracted. A series of logistic regressions were conducted to discern factors related to the odds of having depression. Among study subjects ( N = 3727; age ≥ 58), 20.9% indicated an inclination of having depression (CESD-10 score ≥ 8). This study found that participating in diverse leisure activities and longer exercise time decreases older adults' risk of having depression. Additionally, the results confirmed that depression is positively correlated with chronic diseases. Consequently, efforts should be continually spent on encouraging older adults' participation in activities to reduce the prevalence of depression., Competing Interests: The authors declare no conflict of interest.

In this study, we evaluated the long-term antifungal effectiveness of 3 types of interior building materials (gypsum board [GB], cement board [CB], and softwood plywood [S-PW]) impregnated with thermally reduced silver nanoparticles supported by titanium dioxide (AgNPs/TiO 2 ) under 95% relative humidity for 4 weeks. AgNPs/TiO 2 was synthesized at 2 thermal reduction temperatures (TRTs, 120 and 200°C) with 2 different AgNP weight percentages (2 and 5 wt%). Four different silver-loading levels (SLLs, 0.025, 0.05, and 0.5 μg/cm 2 and the critical concentration required to inhibit fungal growth on agar plates) and 3 fungal species (Aspergillus niger, Penicillium spinulosum, and Stachybotrys chartarum) were used in the experiments. Higher temperature reduced more ionic Ag + to metallic Ag 0 and increased the dispersion of Ag on TiO 2 surface. The 200°C thermally reduced AgNPs/TiO 2 demonstrated excellent antifungal efficiency: Mold growth was almost completely inhibited for 28 days at the low SLL of 0.5 μg/cm 2 . Additionally, AgNPs/TiO 2 exhibited higher antifungal activity on GB and CB than on S-PW. The stepwise regression results indicated that the TRT of AgNPs/TiO 2 (β = -0.739 to -0.51), the SLL (β = -0.477 to -0.269), and the Ag 0 level in the AgNPs (β = -0.379 to -0.136) were the major factors influencing antifungal activity and TRT might be the most significant one., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Albumin-corrected calcium (cCa) is recommended over ionized calcium (iCa) in hemodialysis (HD) patients per the Kidney Disease: Improving Global Outcomes position statements due to cost and feasibility. Two common albumin assays, bromocresol green (BCG) and bromocresol purple (BCP), produce differing results in uremic patients. All previous studies compared iCa to cCa from a BCG assay. This study, using the BCP assay, aimed to compare cCa and total calcium, respectively, to iCa. We also sought to assess phosphate binders and dialysis prescribing patterns following abnormal calcium measurements., Materials and Methods: Retrospective review of 122 stable chronic HD patients with iCa, serum calcium, and albumin measured together throughout 6 blood work periods for a total of 338 sets of comparison values. Payne and Jain calcium correction equations were used. Prescription changes within 2 weeks of abnormal iCa values were recorded., Results: Mean iCa, cCa, and total calcium were 1.17 ± 0.08, 2.37 ± 0.16, and 2.28 ± 0.15 mmol/L, respectively. Total calcium and cCa compared to iCa had κ-coefficients of 0.19 and 0.08, respectively, for hypocalcemia, 0.19 and -0.02 for normocalcemia and 0.59 and 0.46 for hypercalcemia. 21 interventions were made in hypocalcemic patients using iCa as reference; however, if total or corrected calcium values were used, only 8 and 5 interventions, respectively, would result., Conclusion: When BCP assay is used, conventional correction equations should not be utilized in hemodialysis patients; uncorrected serum calcium has a better predictive value.
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Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03μg/g creatinine) (β=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Non-small cell lung cancer (NSCLC) constitutes the main cases of lung cancer and is the world's most common and lethal cancer owing to regional invasion or distant metastasis. Growing morbidity and lethality demonstrates that valid molecular target in management of NSCLC metastasis is still absence. The receptor of advanced glycation end-products (RAGE) has been identified as an oncogenic gene and appears to promote the growth and metastasis of various cancers. Here, we investigated if RAGE targeted by RNA interference (RNAi) might have certain effect on the restraint of the growth of NSCLC and tumor metastasis. Wound healing and Transwell invasion assays indicated that RAGE favored the metastatic capabilities of NSCLC H1975 cells. Besides, soft-agar colony assay revealed that silencing RAGE significantly blocked colony-forming capability of H1975 cells in vitro. Furthermore, we observed that RAGE participated in H1975 cells growth, metastasis and epithelial-mesenchymal transition (EMT) by regulating interdict crux intracellular signaling pathways, including phosphatidylinositol-3 kinase/serine-threonine kinase (PI3K/AKT) and V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog/RAF proto-oncogene serine/threonine-protein kinase (KRAS/RAF-1). In xenograft model, significantly reduction intumor growth and Ki67 expression was demonstrated in nude mice inoculation with RAGE down-regulation H1975 cells. To conclude, our study demonstrated that RAGE played a crucial role in the metastasis and growth of NSCLC by regulating PI3K/AKT and KRAS/RAF-1 signaling pathways, thereby might be a promising therapeutic target for NSCLC., Competing Interests: None.

Relationship between cooking fuel and under-five mortality has not been adequately established in Sub-Saharan Africa (SSA). We therefore investigated the association between cooking fuel and risk of under-five mortality in SSA, and further investigated its interaction with smoking. Using the most recent Demographic Health Survey data of 23 SSA countries (n = 783,691), Cox proportional hazard was employed to determine the association between cooking fuel and risk of under-five deaths. The adjusted hazard ratios were 1.21 (95 % CI, 1.10-1.34) and 1.20 (95 % CI, 1.08-1.32) for charcoal and biomass cooking fuel, respectively, compared to clean fuels. There was no positive interaction between biomass cooking fuel and smoking. Use of charcoal and biomass were associated with the risk of under-five mortality in SSA. Disseminating public health information on health risks of cooking fuel and development of relevant public health policies are likely to have a positive impact on a child's survival.