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Objectives: This study aimed to evaluate the joint effects of multiple air pollutants including PM2.5, PM10, NO2, and NOx with dementia and examined the modifying effects of genetic susceptibility. Methods: This study included 220,963 UK Biobank participants without dementia at baseline. Weighted air pollution score reflecting the joint exposure to multiple air pollutants were constructed by cross-validation analyses, and inverse-variance weighted meta-analyses were performed to create a pooled effect. The modifying effect of genetic susceptibility on air pollution score was assessed by genetic risk score and APOE ε4 genotype. Results: The HR (95% CI) of dementia for per interquartile range increase of air pollution score was 1.13 (1.07â¼1.18). Compared with the lowest quartile (Q1) of air pollution score, the HR (95% CI) of Q4 was 1.26 (1.13â¼1.40) (P trend = 2.17 × 10-5). Participants with high air pollution score and high genetic susceptibility had higher risk of dementia compared to those with low air pollution score and low genetic susceptibility. Conclusion: Our study provides evidence that joint exposure to multiple air pollutants substantially increases the risk of dementia, especially among individuals with high genetic susceptibility.
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Contaminantes Atmosféricos , Contaminación del Aire , Demencia , Humanos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Bancos de Muestras Biológicas , Biobanco del Reino Unido , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Predisposición Genética a la Enfermedad , Demencia/etiología , Demencia/genética , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Material Particulado/efectos adversos , Dióxido de NitrógenoRESUMEN
Current genome-wide association studies of frontotemporal dementia (FTD) are underpowered due to limited samples. Further, common genetic etiologies between FTD and amyotrophic lateral sclerosis (ALS) remain unknown. Using the largest summary statistics of FTD (3526 cases and 9402 controls) and ALS (27,205 cases and 110,881 controls), we found a significant genetic correlation between them (rËg = 0.637, P = 0.032) and identified 190 FTD-related variants within 5 loci (3p22.1, 5q35.1, 9p21.2, 19p13.11, and 20q13.13). Among these, ALS and FTD had causal variants in 9p21.2 and 19p13.11. Moreover, MOBP (3p22.1), C9orf72 (9p21.2), MOB3B (9p21.2), UNC13A (19p13.11), SLC9A8 (20q13.13), SNAI1 (20q13.13), and SPATA2 (20q13.13) were discovered by both SNP- and gene-level analyses, which together discovered 15 FTD-associated genes, with 10 not detected before (IFNK, RNF114, SLC9A8, SPATA2, SNAI1, SCFD1, POLDIP2, TMEM97, G2E3, and PIGW). Functional analyses showed these genes were enriched in heart left ventricle, kidney cortex, and some brain regions. Overall, this study provides insights into genetic determinants of FTD and shared genetic etiology underlying FTD and ALS.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Enfermedad de Pick , Humanos , Demencia Frontotemporal/genética , Esclerosis Amiotrófica Lateral/genética , Estudio de Asociación del Genoma Completo , Mutación , Proteínas/genética , Proteínas Nucleares/genéticaRESUMEN
AIMS: The relationship between the long-term joint exposure to ambient air pollution and incidence of myocardial infarction (MI) and modification by genetic susceptibility remain inconclusive. METHODS AND RESULTS: We analysed 329 189 UK Biobank participants without MI at baseline. Exposure concentrations to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were obtained. Air pollution score assessing the joint exposure was calculated, and its association with MI was evaluated via Cox model under the P value aggregation framework. Genetic susceptibility to MI was evaluated by incorporating polygenic risk score (PRS) into models. Risk prediction models were also established. During a median follow-up of 13.4 years, 9993 participants developed MI. Per interquartile range increase of PM2.5, PM10, NO2, and NOx resulted in 74% [95% confidence intervals (CIs) 69%-79%], 67% (63%-72%), 46% (42%-49%), and 38% (35%-41%) higher risk of MI. Compared with the lowest quartile (Q1) of air pollution score, the multivariable adjusted hazard ratio (HR) (95%CIs) of Q4 (the highest cumulative air pollution) was 3.50 (3.29-3.72) for MI. Participants with the highest PRS and air pollution score possessed the highest risk of incident MI (HR = 4.88, 95%CIs 4.35-5.47). Integrating PRS, air pollution exposure, and traditional factors substantially improved risk prediction of MI. CONCLUSION: Long-term joint exposure to air pollutants including PM2.5, PM10, NO2, and NOx is substantially associated with increased risk of MI. Genetic susceptibility to MI strengthens such adverse joint association. Air pollutions together with genetic and traditional factors enhance the accuracy of MI risk prediction.
Our study aimed to analyse the relationship between the long-term joint exposure to four ambient air pollutants and incidence of myocardial infarction (MI), and the modification role of genetic susceptibility. Four air pollutants (PM2.5, PM10, NO2, and NOx) were adversely associated with the incidence of MI as well as with its two subtypes including ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI). Air pollution score representing co-exposure to multiple air pollutants was related to increased risk of incident MI, STEMI, and NSTEMI. Genetic susceptibility to MI strengthened the adverse association of co-exposure to air pollution with the risk of MI, STEMI, and NSTEMI.
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Contaminantes Atmosféricos , Contaminación del Aire , Infarto del Miocardio , Humanos , Contaminantes Atmosféricos/efectos adversos , Dióxido de Nitrógeno/análisis , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Exposición a Riesgos Ambientales/efectos adversos , Contaminación del Aire/efectos adversos , Material Particulado/efectos adversos , Estudios de Cohortes , Óxidos de Nitrógeno , Predisposición Genética a la Enfermedad , Puntuación de Riesgo GenéticoRESUMEN
Long-wavelength broadband near-infrared (NIR) phosphors have attracted considerable interest in the fields of medical cosmetology and organic detection because of their special emission band. Herein, Ca2GeO4(CGO): Cr4+ NIR phosphor, presenting a broadband emission with longer wavelength ranging from 1100 to 1600 nm, has been synthesized. Further, the luminescence intensity and quantum efficiency of Cr4+ could be obviously improved via the energy transfer from Eu3+ to Cr4+. The energy transfer is dominated by the dipole-dipole mechanism, which can be inferred from the spectra and the decay curves. Furthermore, in order to evaluate the potential application, an NIR phosphor-converted light-emitting diode (pc-LED) based on blue chip has been prepared. Consequently, CGO: Eu3+, Cr4+ exhibits proper output power and wider half-width than the NIR LED chip, indicating its great prospect for long-wavelength NIR pc-LED applications.
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Near-infrared (NIR) light has attracted considerable attention in diverse applications, such as food testing, security monitoring, and modern agriculture. Herein, the advanced applications of NIR light, as well as various devices to realize NIR light, have been described. Among the diverse NIR light source devices, the NIR phosphor-converted light-emitting diode (pc-LED), serving as a new-generation NIR light source, has obtained attention due to its wavelength-tunable behavior and low-cost. As one of the key materials of the NIR pc-LED, a series of NIR phosphors have been summarized depending on the type of luminescence center. Meanwhile, the characteristic transitions and luminescence properties of the above phosphors are illustrated in detail. In addition, the status quo of NIR pc-LEDs, as well as the potential problems and future developments of NIR phosphors and applications have also been discussed.
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Phosphor-converted white-light-emitting diodes (pc-wLEDs) have attracted considerable attention in general lighting and backlight display applications due to their high efficiency and long lifetime. The combination of Ce3+-doped yttrium aluminium garnet (YAG:Ce3+) with a blue LED chip is the most mature technology to obtain white light emission. Because of the excellent structural flexibility of garnet, many novel garnet phosphors have been designed and developed in the past few years. In this Frontier article, we describe our results related to the modification and calculation of garnet phosphors. The modification of YAG:Ce3+ phosphors is divided into five types depending on the crystallographic sites of substitution, and the effects of each on the structure and luminescence properties are illustrated in detail. Additionally, we outline our recent research progress in first-principles calculations of garnet phosphors with an emphasis on the analysis and prediction of their structure and luminescence performance. Finally, the status quo of pc-wLEDs using garnet phosphors, as well as the potential problems and future developments of garnet phosphors, are also discussed.