| 41. |
- Chen, M-J, et al.
(författare)
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Body mass index and breast cancer : analysis of a nation-wide population-based prospective cohort study on 1 393 985 Taiwanese women
- 2016
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 40:3, s. 524-530
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The link between obesity and risk of breast cancer in Asian women is still elusive. We aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women.METHODS: A total of 1 393 985 women who had been cancer-free before recruitment and attended a nation-wide Taiwanese breast cancer-screening program between 1999 and 2009 were enrolled using a prospective cohort study. Obesity and other relevant variables (such as menopause status and other biochemical markers) were collected through in-person interviews, anthropometric measurements and blood samples at first screen. Incident breast cancers during follow-up were ascertained through the linkage of the cohort with the National Cancer Registry and the National Death Certification System.RESULTS: A total of 6969 and 7039 incident breast cancer cases were identified among women enrolled before and after menopause, respectively. Compared with a BMI range of 18.5-23.9 kgm(-2), the incremental level of BMI in the enrolled women before menopause revealed a lack of statistically significant association with the risk of incident breast cancer (adjusted hazard ratio = 0.94, 0.98, 1.02, 1.01 and 0.82 for BMI < 18.5, 24-26.9, 27-29.9, 30-34.9 and >= 35, respectively), but the incremental level of BMI in the enrolled women after menopause led to a statistically significant incremental increase in the risk of breast cancer (adjusted hazard ratio = 0.78, 1.19, 1.31, 1.53 and 1.65 for BMI < 18.5, 24-26.9, 27-29.9, 30-34.9 and >= 35, respectively) after adjusting for other explanatory risk factors.CONCLUSION: Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women.
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| 42. |
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| 43. |
- Chen, Ying, et al.
(författare)
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Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
- 2015
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Ingår i: Molecular Cancer Therapeutics. - 1538-8514. ; 14:1, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and is previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. beta-catenin was determined by immunohistochemistry, PAF levels by ELISA and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared to WT mice. While all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared to WT mice, cytosol expression of beta-catenin was significantly decreased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion lack of alk-SMase markedly increases AOM/DSS induced colonic tumorigenesis associated with decreased ceramide and increased sphingosine-1-phosphate and PAF levels.
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| 44. |
- Chen, Yi-Jing, et al.
(författare)
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Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting
- 2023
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773.
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Tidskriftsartikel (refereegranskat)abstract
- The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 mu A cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems. Three perylene diimide (PDI) polymers were designed and synthesized such that the molecular orientation of the PDI units was regulated to create and modulate their built-in electric fields. Due to the large dipole moment and interfacial electric field, oPDI enables an extraordinary photocurrent density of 115.1 mu A & sdot; cm-2, which is 11.5 and 26.8 times that of mPDI and pPDI, respectively.image
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| 45. |
- Chen, Ziqing, et al.
(författare)
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Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25(+)/CD54(+) NK cells
- 2021
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Ingår i: EMBO Reports. - : EMBO Press. - 1469-221X .- 1469-3178. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Inadequate persistence of tumor-infiltrating natural killer (NK) cells is associated with poor prognosis in cancer patients. The solid tumor microenvironment is characterized by the presence of immunosuppressive factors, including prostaglandin E2 (PGE2), that limit NK cell persistence. Here, we investigate if the modulation of the cytokine environment in lung cancer with IL-2 or IL-15 renders NK cells resistant to suppression by PGE2. Analyzing Cancer Genome Atlas (TCGA) data, we found that high NK cell gene signatures correlate with significantly improved overall survival in patients with high levels of the prostaglandin E synthase (PTGES). In vitro, IL-15, in contrast to IL-2, enriches for CD25(+)/CD54(+) NK cells with superior mTOR activity and increased expression of the cAMP hydrolyzing enzyme phosphodiesterase 4A (PDE4A). Consequently, this distinct population of NK cells maintains their function in the presence of PGE2 and shows an increased ability to infiltrate lung adenocarcinoma tumors in vitro and in vivo. Thus, strategies to enrich CD25(+)/CD54(+) NK cells for adoptive cell therapy should be considered.
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| 46. |
- Dan, Meng, et al.
(författare)
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A dual-interfacial system with well-defined spatially separated redox-sites for boosting photocatalytic overall H2S splitting
- 2021
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 423
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Tidskriftsartikel (refereegranskat)abstract
- Integration of high activity, selectivity, and stability is urgently desired to achieve more ideal photocatalysts. Herein, we reported the rational design of MoS2-MnS@(InxCu1-x)2S3 (M-M@IC) catalysts with dual interface to integrate separated redox sites for boosting photocatalytic hydrogen sulphide (H2S) splitting and the resource utilization of sacrificial reagents (Na2S/Na2SO3). The spatially separated reduction (MnS) and oxidation (In2S3) sites in MnS/In2S3 heterojunction, on which MoS2 and Cu were selectively loaded, can drive electrons and holes near the surface to flow along opposite directions, while the heterojunction between MnS and In2S3 inhibits the bulk charge recombination. Furthermore, the introduction of Cu atoms creates a d-band center, which favours mass diffusion of reactants/products species and greatly facilitates sunlight response. The MoS2 serves to provide abundant sites for proton reduction due to the unsaturated-sulfur-edge-rich (US-rich) nature. As a result, the M−M@IC shows a state-of-the-art visible-light photocatalytic H2 evolution rate (126.5 mmol g-1h−1), inspiring stability of >50 h, and nearly 100% selectivity toward value-added Na2S2O3 production under optimized condition. This work opens up new opportunities for the construction and design of spatially separated catalytic site in photocatalysts.
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| 47. |
- Dan, Meng, et al.
(författare)
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Beyond hydrogen production : Solar−driven H2S−donating value−added chemical production over MnxCd1−xS/CdyMn1−yS catalyst
- 2021
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Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373. ; 284
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneous hydrogen (H2) evolution and value−added chemicals production are highly attractive but have not drawn enough attention. Here, we demonstrate a hydrogen sulphide (H2S)−induced product−targeting (HIPT) strategy for the coproduction of H2 and valuable chemical feedstocks from Na2S/Na2SO3 via overall H2S splitting using a MnxCd1−xS/CdyMn1−yS catalyst driven by visible light excitation. With this chemistry, 113 mmol g−1 h−1 of hydrogen evolution rate is achieved, surpassing most of the previously reported state-of-the-art photocatalyst, together with the production of value−added Na2S2O3 with nearly 100% selectivity. This work not only provides a good example for solar energy conversion via overall H2S splitting, but also offers new insights into the resource utilization of sacrificial donor (Na2S/Na2SO3) in various catalytic fields such as H2O splitting and CO2 reduction.
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| 48. |
- Dastani, Zari, et al.
(författare)
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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
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Tidskriftsartikel (refereegranskat)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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| 49. |
- Delgado-Vega, Angélica M., et al.
(författare)
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Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:7, s. 1219-1226
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE).MethodsGenotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was done using PLINK and conditional analyses using GENABEL's test score. Transfections of BLK constructs on HEK293 cells containing the novel mutation or the wild type form were analysed for their effect on protein half-life using a protein stability assay, cycloheximide and western blot. CHiP-qPCR for detection of nuclear factor. B (NFkB) binding.ResultsFine mapping of BLK identified two independent genetic effects with functional consequences: one represented by two tightly linked associated haplotype blocks significantly enriched for NF kappa B-binding sites and numerous putative regulatory variants whose risk alleles correlated with low BLK mRNA levels. Binding of NFkBp50 and p65 to an associated 1.2 Kb haplotype segment was confirmed. A second independent genetic effect was represented by an Ala71Thr, low-frequency missense substitution with an OR = 2.31 (95% CI 1.38 to 3.86). The 71Thr decreased BLK protein half-life.ConclusionsThese results show that rare and common regulatory variants in BLK are involved in disease susceptibility and both, albeit independently, lead to reduced levels of BLK protein.
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| 50. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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