| 51. |
- Ai, Sizhi, et al.
(författare)
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Causal associations of short and long sleep durations with 12 cardiovascular diseases : linear and nonlinear Mendelian randomization analyses in UK Biobank
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:34, s. 3349-3357
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Tidskriftsartikel (refereegranskat)abstract
- Aims Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. Methods and results Genetic variants associated with continuous, short (<= 6 h) and long (>= 9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P <0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P< 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. Conclusion This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long steep duration is unlikely to be a causal risk factor for most CVDs. [GRAPHICS] .
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| 52. |
- Bueno Pérez, Lynette, et al.
(författare)
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Caeruleanone A, a rotenoid with a new arrangement of the D-ring from the fruits of Millettia caerulea.
- 2014
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 16:5, s. 1462-1465
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Tidskriftsartikel (refereegranskat)abstract
- Caeruleanone A (1), a novel rotenoid with an unprecedented arrangement of the D-ring, was isolated with another two new analogues, caeruleanones B (2) and C (3), together with 11 known rotenoids from the fruits of Millettia caerulea. The structures of the new compounds were determined by spectroscopic data analysis, with that of 1 being confirmed by single-crystal X-ray diffraction. Compounds 2 and 3 displayed potent mitochondrial transmembrane potential inhibitory and quinone reductase induction activities.
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| 53. |
- Cao, Huiming, et al.
(författare)
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Effect of Enterohepatic Circulation on the Accumulation of Per- and Polyfluoroalkyl Substances : Evidence from Experimental and Computational Studies
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:5, s. 3214-3224
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetic characteristics of per- and polyfluoroalkyl substances (PFAS) affect their distribution and bioaccumulation in biological systems. The enterohepatic circulation leads to reabsorption of certain chemicals from bile back into blood and the liver and thus influences their elimination, yet its influence on PFAS bioaccumulation remains unclear. We explored the role of enterohepatic circulation in PFAS bioaccumulation by examining tissue distribution of various PFAS in wild fish and a rat model. Computational models were used to determine the reabsorbed fractions of PFAS by calculating binding affinities of PFAS for key transporter proteins of enterohepatic circulation. The results indicated that higher concentrations were observed in blood, the liver, and bile compared to other tissues for some PFAS in fish. Furthermore, exposure to a PFAS mixture on the rat model showed that the reabsorption phenomenon appeared during 8-12 h for most long-chain PFAS. Molecular docking calculations suggest that PFAS can bind to key transporter proteins via electrostatic and hydrophobic interactions. Further regression analysis adds support to the hypothesis that binding affinity of the apical sodium-dependent bile acid transporter is the most important variable to predict the human half-lives of PFAS. This study demonstrated the critical role of enterohepatic circulation in reabsorption, distribution, and accumulation of PFAS.
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| 54. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 55. |
- Chen, Guanying, et al.
(författare)
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(alpha-NaYbF4:Tm3+)/CaF2 Core/Shell Nanoparticles with Efficient Near-Infrared to Near-Infrared Upconversion for High-Contrast Deep Tissue Bioimaging
- 2012
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 6:9, s. 8280-8287
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Tidskriftsartikel (refereegranskat)abstract
- We describe the development of novel and biocompatible core/shell (alpha-NaYbF4:Tm3+)/CaF2 nanoparticles that exhibit highly efficient NIRin-NIROut upconversion (UC) for high contrast and deep bioimaging. When excited at similar to 980 nm, these nanoparticles emit photoluminescence (PL) peaked at similar to 800 nm. The quantum yield of this UC PL under low power density excitation (similar to 0.3 W/cm(2)) is 0.6 +/- 0.1%. This high UC PL efficiency is realized by suppressing surface quenching effects via heteroepitaxial growth of a biocompatible CaF2 shell, which results in a 35-fold increase in the intensity of UC PL from the core. Small-animal whole-body UC PL imaging with exceptional contrast (signal-to-background ratio of 310) is shown using BALB/c mice intravenously injected with aqueously dispersed nanoparticles (700 pmol/kg). High-contrast UC PL imaging of deep tissues is also demonstrated, using a nanoparticle-loaded synthetic fibrous mesh wrapped around rat femoral bone and a cuvette with nanoparticle aqueous dispersion covered with a 3.2 cm thick animal tissue (pork).
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| 56. |
- Chen, Jing-De, et al.
(författare)
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Hot-electron emission-driven energy recycling in transparent plasmonic electrode for organic solar cells
- 2022
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Ingår i: InfoMat. - : Wiley. - 2567-3165. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Plasmonic metal electrodes with subwavelength nanostructures are promising for enhancing light harvesting in photovoltaics. However, the nonradiative damping of surface plasmon polaritons (SPPs) during coupling with sunlight results in the conversion of the excited hot-electrons to heat, which limits the absorption of light and generation of photocurrent. Herein, an energy recycling strategy driven by hot-electron emission for recycling the SPP energy trapped in the plasmonic electrodes is proposed. A transparent silver-based plasmonic metal electrode (A-PME) with a periodic hexagonal nanopore array is constructed, which is combined with a luminescent organic emitter for radiative recombination of the injected hot-electrons. Owing to the suppressed SPP energy loss via broadband hot-electron emission, the A-PME achieves an optimized optical transmission with an average transmittance of over 80% from 380 to 1200 nm. Moreover, the indium-tin-oxide-free organic solar cells yield an enhanced light harvesting with a power conversion efficiency of 16.1%.
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| 57. |
- Chen, Jie, et al.
(författare)
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Gastrointestinal Consequences of Type 2 Diabetes Mellitus and Impaired Glycemic Homeostasis : A Mendelian Randomization Study
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:4, s. 828-835
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs).RESEARCH DESIGN AND METHODS: Uncorrelated genetic variants associated with type 2 diabetes (n = 231), fasting insulin (n = 38), fasting glucose (n = 71), and hemoglobin A1c (n = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with 23 common GDs were obtained from the FinnGen and UK Biobank studies and other large consortia.RESULTS: Genetic liability to type 2 diabetes was associated with the risk of 12 GDs. Per 1-unit increase in the log-transformed odds ratio (OR) of type 2 diabetes, the OR was 1.06 (95% CI, 1.03-1.09) for gastroesophageal reflux disease, 1.12 (95% CI, 1.07-1.17) for gastric ulcer, 1.11 (95% CI, 1.03-1.20) for acute gastritis, 1.07 (95% CI, 1.01-1.13) for chronic gastritis, 1.08 (95% CI, 1.03-1.12) for irritable bowel syndrome, 1.04 (95% CI, 1.01-1.07) for diverticular disease, 1.08 (95% CI, 1.02-1.14) for acute pancreatitis, 1.09 (95% CI, 1.05-1.12) for cholelithiasis, 1.09 (95% CI, 1.05-1.13) for cholelithiasis with cholecystitis, 1.29 (95% CI, 1.17-1.43) for nonalcoholic fatty liver disease, 1.12 (95% CI, 1.03-1.21) for liver cirrhosis, and 0.93 (95% CI, 0.89-0.97) for ulcerative colitis. Genetically predicted higher levels of fasting insulin and glucose were associated with six and one GDs, respectively.CONCLUSIONS: Associations were found between genetic liability to type 2 diabetes and an increased risk of a broad range of GDs, highlighting the importance of GD prevention in patients with type 2 diabetes.
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| 58. |
- Chen, Jie, et al.
(författare)
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Risk of incident cardiovascular disease among patients with gastrointestinal disorder : a prospective cohort study of 330,751 individuals.
- 2023
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - 2058-5225 .- 2058-1742.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The associations between gastrointestinal diseases (GIs) and cardiovascular disease (CVD) were unclear. We conducted a prospective cohort study to explore their associations.METHODS: This study included 330 751 individuals without baseline CVD from the UK Biobank cohort. Individuals with and without GIs were followed up until the ascertainment of incident CVDs, including coronary heart disease (CHD), cerebrovascular disease (CeVD), heart failure (HF) and peripheral artery disease (PAD). The diagnosis of diseases was confirmed with combination of the nationwide inpatient data, primary care data, and cancer registries. A multivariable Cox proportional hazard regression model was used to estimate the associations between GIs and the risk of incident CVD.RESULTS: During a median follow-up of 11.8 years, 31 605 incident CVD cases were diagnosed. Individuals with GIs had an elevated risk of CVD (hazard ratio 1.37; 95% confidence interval 1.34-1.41, P < 0.001). Eleven out of fifteen GIs were associated with an increased risk of CVD after Bonferroni-correction, including cirrhosis, non-alcoholic fatty liver disease, gastritis and duodenitis, irritable bowel syndrome, Barrett's esophagus, gastroesophageal reflux disease, peptic ulcer, celiac disease, diverticulum, appendicitis, and biliary disease. The associations were stronger among women, individuals aged ≤ 60 years, and those with body mass index ≥ 25 kg/m2.CONCLUSIONS: This large-scale prospective cohort study revealed the associations of GIs with an increased risk of incident CVD, in particular CHD and PAD. These findings support the reinforced secondary CVD prevention among patients with gastrointestinal disorders.
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| 59. |
- Chen, Jie, et al.
(författare)
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Therapeutic targets for inflammatory bowel disease : proteome-wide Mendelian randomization and colocalization analyses
- 2023
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying new drug targets for inflammatory bowel disease (IBD) is urgently needed. The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) and colocalization analyses to identify possible targets for IBD.Methods: Summary-level data of 4907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals. Genetic associations with IBD and its subtypes were obtained from the Inflammatory Bowel Disease Genetics Consortium (25,024 cases and 34,915 controls), the FinnGen study (7206 cases and 253,199 controls), and the UK Biobank study (7045 cases and 449,282 controls). MR analysis was conducted to estimate the associations between protein and IBD risk. The colocalization analysis was used to examine whether the identified proteins and IBD shared casual variants.Findings: Genetically predicted levels of 3, and 5 circulating proteins were associated with IBD and ulcerative colitis (UC), respectively. With high supporting evidence of colocalization, genetically predicted MST1 (macrophage stim-ulating 1) and HGFAC (hepatocyte growth factor activator) levels were inversely associated with IBD risks. The as-sociations of STAT3 (signal transducer and activator of transcription 3), MST1, CXCL5 (C-X-C motif chemokine ligand 5), and ITPKA (inositol-trisphosphate 3-kinase A) with the risk of UC were supported by colocalization analysis.Interpretation: The proteome-wide MR investigation identified many proteins associated with the risk of IBD. MST1, HGFAC, STAT3, ITPKA, and CXCL5 deserve further investigation as potential therapeutic targets for IBD. 2023;89: Published https://doi.org/10. 1016/j.ebiom.2023. 104494
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| 60. |
- Chen, Ling, et al.
(författare)
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Reliable and efficient RAR-based distributed model training in computing power network
- 2024
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Ingår i: Journal of Optical Communications and Networking. - 1943-0620 .- 1943-0639. ; 16:5, s. 527-540
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Tidskriftsartikel (refereegranskat)abstract
- The computing power network (CPN) is a novel network technology that integrates computing power from the cloud, edge, and terminals using IP/optical cross-layer networks for distributed computing. CPNs can provide an effective solution for distributed model training (DMT). As a bandwidth optimization architecture based on data parallelism, ring all-reduce (RAR) is widely used in DMT. However, any node or link failure on the ring can interrupt or block the requests deployed on the ring. Meanwhile, due to the resource competition of batch RAR-based DMT requests, inappropriate scheduling strategies will also lead to low training efficiency or congestion. As far as we know, there is currently no research that considers the survivability of rings in scheduling strategies for RAR-based DMT. To fill this gap, we propose a scheduling scheme for RAR-based DMT requests in CPNs to optimize the allocation of computing and wavelength resources considering the time dimension while ensuring reliability. In practical scenarios, service providers may focus on different performance metrics. We formulate an integer linear programming (ILP) model and a RAR-based DMT deployment algorithm (RDDA) to solve this problem considering four optimization objectives under the premise of the minimum blocking rate: minimum computing resource consumption, minimum wavelength resource consumption, minimum training time, and maximum reliability. Simulation results demonstrate that our model satisfies the reliability requirements while achieving corresponding optimal performance for DMT requests under four optimization objectives.
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