SwePub - search: WFRF:(Liu Chunyu)

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1.	Cao, Ling, et al. (author) Vulnerability of blue foods to human-induced environmental change 2023 In: Nature Sustainability. - 2398-9629. ; 6, s. 1186-1198 Journal article (peer-reviewed)abstract Global aquatic foods are a key source of nutrition, but how their production is influenced by anthropogenic environmental changes is not well known. The vulnerability of global blue food systems to main environmental stressors and the related spatial impacts across blue food nations are now quantified. Global aquatic or 'blue' foods, essential to over 3.2 billion people, face challenges of maintaining supply in a changing environment while adhering to safety and sustainability standards. Despite the growing concerns over their environmental impacts, limited attention has been paid to how blue food production is influenced by anthropogenic environmental changes. Here we assess the vulnerability of global blue food systems to predominant environmental disturbances and predict the spatial impacts. Over 90% of global blue food production faces substantial risks from environmental change, with the major producers in Asia and the United States facing the greatest threats. Capture fisheries generally demonstrate higher vulnerability than aquaculture in marine environments, while the opposite is true in freshwater environments. While threats to production quantity are widespread across marine and inland systems, food safety risks are concentrated within a few countries. Identifying and supporting mitigation and adaptation measures in response to environmental stressors is particularly important in developing countries in Asia, Latin America and Africa where risks are high and national response capacities are low. These findings lay groundwork for future work to map environmental threats and opportunities, aiding strategic planning and policy development for resilient and sustainable blue food production under changing conditions.
2.	Schumann, Gunter, et al. (author) KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference 2016 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377 Journal article (peer-reviewed)abstract Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
3.	Kraja, Aldi T., et al. (author) New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals 2017 In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5 Journal article (peer-reviewed)abstract Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
4.	Ma, Jiantao, et al. (author) A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Nonalcoholic Fatty Liver Disease 2019 In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 68:5, s. 1073-1083 Journal article (peer-reviewed)abstract Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10(-6)) with replication at Bonferroni-corrected P < 8.6 x 10(-4). Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10(-4)). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood-derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat-associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.
5.	Mueller, Christian P., et al. (author) The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study 2019 In: Cerebral Cortex. - : OXFORD UNIV PRESS INC. - 1047-3211 .- 1460-2199. ; 29:4, s. 1736-1751 Journal article (peer-reviewed)abstract Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
6.	Smith, Gustav, et al. (author) Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure 2016 In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5 Journal article (peer-reviewed)abstract Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
7.	Surendran, Praveen, et al. (author) Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals 2020 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332 Journal article (peer-reviewed)abstract Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
8.	Wessel, Jennifer, et al. (author) Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility 2015 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6 Journal article (peer-reviewed)abstract Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
9.	Cardona, Alexia, et al. (author) Epigenome-wide association study of incident type 2 diabetes in a British population : EPIC-Norfolk study 2019 In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:12, s. 2315-2326 Journal article (peer-reviewed)abstract Epigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the populationbased European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesityrelated pathways acting before the collection of baseline samples.We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia.
10.	Chen, Chunyu, et al. (author) Equilibrium of Frequency Control Ancillary Service Market Based on Attack-defense Game 2024 In: Dianwang Jishu/Power System Technology. - : Power System Technology Press. - 1000-3673. ; 48:2, s. 679-687 Journal article (peer-reviewed)abstract With the improvement of electricity market rules, the power system operator permits new energy resources to gradually participate in the frequency control ancillary service market. The participation of new energy resources greatly enhance the frequency regulation performance and mutual support of different energy resources. However, some frequency regulation resources are usually equipped with insufficient cyber security protection measures due to economic considerations. Under this situation, hackers may exploit the vulnerability of susceptible cyber physical systems to disrupt the operation of frequency control ancillary service market. Therefore, we analyze frequency modulation market game equilibrium considering the attack-defense game. First, we analyze the cyber attack behaviors aiming at manipulating the bidding information of susceptible resources. Second, we analyze the attack model aiming at maximizing the profit of the complicity. Next, a frequency modulation market equilibrium model considering the master-slave Stackelberg game of both sides of attack and defense is designed. Finally, the frequency modulation market equilibrium results based on the Column-and-Constraint Generation (C&CG) algorithm are analyzed. Through case analysis of 30-unit frequency regulation markets, the average deviation of capacity revenue change from 113.89% under attack to 12.56% after defense, indicating that the defender can to a certain extent suppress the market equilibrium deviation caused by the attacker.
11.	Cheng, Qiaoyun, et al. (author) The conversion of nanocellulose into solvent-free nanoscale liquid crystals by attaching long side-arms for multi-responsive optical materials 2020 In: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 8:32, s. 11022-11031 Journal article (peer-reviewed)abstract Nanocellulose, with its unique optical and chemical properties, has received increasing attention as feedstock to fabricate sustainable materials. However, achieving a nanocellulose-based solvent-free liquid crystal with good responsiveness still remains a challenge. Herein, for the first time, solvent-free supramolecular liquid crystals were fabricated by attaching long side-arms on the fiber-like nanocellulose derived from tunicate (TCNC) with an average width of 20 nm and 400-3000 nm in length. The side-arms were grafted via surface condensation with a charged organosilane, followed by further functionalization with a counter-ion polyoxyethylene ether. The nanoscale liquid crystals consisted of the stiff TCNC as the core and flexible side-arms as the soft shells, forming the core-shell structure with an average width of 34-36 nm. The resulting solvent-free liquid crystal exhibited transparent and viscous liquid-like fluidity, as well as a bright birefringence between the crossed polarizers at room temperature. In our findings, the stiff core provided crystal-like ordering, whereas the soft shells induced the high mobility of the TCNCs as a result of the increased fractional free volume, as shown by positron annihilation lifetime spectra. The unique flowability enables the possibility of multi-responsiveness to temperature, deformation, and alternating electric fields. In addition, the thermo-responsiveness can be regulated by tailoring the canopy. This work provides a novel strategy for the conversion of solid nanocellulose into a solvent-free nanoscale liquid crystal, which is promising for use as a responsive optical material.
12.	Demerath, Ellen W., et al. (author) Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci 2015 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:15, s. 4464-4479 Journal article (peer-reviewed)abstract Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 x 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.
13.	Fedorowski, Artur, et al. (author) Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium. 2012 In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:18, s. 2331-2341 Journal article (peer-reviewed)abstract Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
14.	Hedman, Åsa K., et al. (author) Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies 2017 In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:1 Journal article (peer-reviewed)abstract Background- Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. Methods and Results- To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P < 1.08E-07) and replicated 33 (at Bonferroni-corrected P < 0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglyceridesand high-density lipoprotein cholesterol (HDL- C; cg27243685; P= 8.1E-26 and 9.3E-19) was associated with cis-expression of a reverse cholesterol transporter (ABCG1; P= 7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P= 0.0007). We found significant cis-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (P-TC = 0.004, PHDL-C = 0.008 and P-triglycerides = 0.00003) and coronary heart disease ( P= 0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. Conclusions-We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events.
15.	Hou, Liping, et al. (author) Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. 2016 In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94 Journal article (peer-reviewed)abstract Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
16.	Huan, Tianxiao, et al. (author) Genome-wide identification of DNA methylation QTLs in whole blood highlights pathways for cardiovascular disease 2019 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10 Journal article (peer-reviewed)abstract Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in whole blood from 4170 individuals and map 4.7 million cis- and 630 thousand trans-meQTL variants targeting >120 thousand CpGs. Independent replication is performed in 1347 participants from two studies. By linking cis-meQTL variants with GWAS results for cardiovascular disease (CVD) traits, we identify 92 putatively causal CpGs for CVD traits by Mendelian randomization analysis. Further integrating gene expression data reveals evidence of cis CpG-transcript pairs causally linked to CVD. In addition, we identify 22 trans-meQTL hotspots each targeting more than 30 CpGs and find that trans-meQTL hotspots appear to act in cis on expression of nearby transcriptional regulatory genes. Our findings provide a powerful meQTL resource and shed light on DNA methylation involvement in human diseases.
17.	Li, Zhiqi, et al. (author) Efficient perovskite solar cells enabled by ion-modulated grain boundary passivation with a fill factor exceeding 84% 2019 In: Journal of Materials Chemistry A. - : ROYAL SOC CHEMISTRY. - 2050-7488 .- 2050-7496. ; 7:39, s. 22359-22365 Journal article (peer-reviewed)abstract Alkali metal cation modulation toward high-electronic-quality perovskite films requires strict control over trap densities in the devices. By introducing tailor-made potassium cation (K+)-functionalized carbon nanodots (CNDs@K) into the perovskite precursor solution, we succeeded in defect passivation and crystallization control of the perovskite film. X-ray diffraction indicated that the binding effect of carbon dots confined the K+ ions in the grain boundary and prevented excessive cations from occupying interstitial sites, thereby reducing the microstrain of the polycrystalline film. Consequently, the synergistic effect of the tailored crystal size and suppressed grain boundary defects could reduce the charge trap density, facilitate charge generation, and lengthen the carrier lifetime, leading to a boosted efficiency of 21.01% with a high fill factor of 84%. This performance is among the best reported for carbon dot-doped PSCs.
18.	Liu, Chunyu, et al. (author) Experimental study on effects of ammonia enrichment on the thermoacoustic instability of lean premixed swirling methane flames 2024 In: Fuel. - 0016-2361. ; 357 Journal article (peer-reviewed)abstract Ammonia (NH3) has recently emerged as a promising carbon-free energy carrier. Further development and application of NH3 as fuel in the gas turbine industry can significantly reduce the emissions of carbon dioxide (CO2) and contribute to the achievement of a carbon–neutral society. This study experimentally examined the thermoacoustic instability characteristics of a laboratory-scaled lean premixed gas turbine model combustor operated with different NH3 blending ratios with methane (CH4). Experiments conducted under a wide range of inlet velocities and equivalence ratios suggest that NH3 concentration is critical in determining the characteristics of the instability. Specifically, when the NH3 proportion is less than 50 %, the addition of NH3 causes a mode transition of the instability. However, when the content of NH3 is greater than 50 %, it is shown that the instabilities are suppressed, indicating that the addition of a certain amount of NH3 can enhance the stability of CH4 flames. Additional analysis of flame dynamics reveals that the introduction of NH3 causes the lengthening of the flame front and weakens heat release rate fluctuations in the flame root regions. Further Proper Orthogonal Decomposition (POD) analysis of the flow field shows that the instability modes are strongly coupled with periodic vortex motions of the flow dynamics along the shear layers. Finally, the mode shifting phenomena is successfully predicted by low-order thermoacoustic network modeling. It is suggested that the change in convective time delay caused by NH3 addition is responsible for such transitions.
19.	Liu, Chunyu, et al. (author) Influence of swirl intensity on combustion dynamics and emissions in an ammonia-enriched methane/air combustor 2024 In: Physics of Fluids. - 1070-6631. ; 36:3 Journal article (peer-reviewed)abstract Ammonia (NH3) has been widely considered as a promising carbon-free energy and hydrogen carrier for various applications. The large-scale direct utilization of NH3 as fuel in gas turbine engines is currently attracting significant interest, with strong focuses on improving the efficiency and stability of the system and reducing the emissions of pollutants. The present study experimentally examined the impacts of swirl intensity on combustion stability and emissions in an NH3-enriched premixed swirl-stabilized CH4/air combustor under a wide range of equivalence ratios. Simultaneous high-speed OH* chemiluminescence and particle image velocimetry measurements suggested that increasing swirl intensity resulted in more compact flame shapes and expanded the recirculation zone, which promoted flame stability at higher NH3 ratios. However, under specified conditions, enhancing swirl intensity could increase the instability frequency and amplitude of pressure oscillations. The flame dynamics exhibited different behaviors depending on the swirl intensity. At high swirl intensity, the flames underwent high-frequency, small-amplitude periodic motion. At low swirl intensity, the flames oscillated axially with large amplitude and low frequency. For flow dynamics, the stability of the vortex at high swirl intensity contrasted with the periodic vortex shedding at low swirl intensity. Furthermore, the two-dimensional Rayleigh index indicated that the dominant positive thermoacoustic coupling regions were located near the flame shear layers and flame tail at low and high swirl intensities, respectively. Finally, the experimental results showed that swirl intensity affected pollutant emissions by influencing the temperature of combustion chamber and gas mixing efficiency. The pathway of fuel-type NOx was found to be dominant in the NOx emission of the NH3/CH4/air flames.
20.	Mendelson, Michael M., et al. (author) Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease : A Mendelian Randomization Approach 2017 In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:1 Journal article (peer-reviewed)abstract Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.
21.	Qin, Wenjing, et al. (author) Surface states of ZnO nanoparticles effect on the performance of inverted-organic solar cells 2013 In: Journal of Renewable and Sustainable Energy. - : American Institute of Physics (AIP). - 1941-7012. ; 5:5 Journal article (peer-reviewed)abstract ZnO is a promising material used as the electron transport layer in the inverted organic solar cells (IOSCs). However, the electrical or photoelectric properties of ZnO nanoparticles are governed by the surface states of the nanoparticles. Here, we demonstrate that the large number of hydroxyl (-OH) existed on the ZnO nanoparticles films have a vast impact on the performance of IOSCs with the structure of ITO/ZnO/poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C-61 butyric acid methyl ester (PCBM)/MoO3/Ag. The surface hydroxyl groups depredate active layer via elevating photocatalytic activity of the ZnO, hence deteriorate the device performance. Experimental results show that hydroxyl groups can be effectively detached from ZnO film by annealing. Hydroxyl groups detach more with increasing annealing temperature, resulting in less degradation of the active layer. Therefore, the efficiency is significantly improved due to increased photo-current density and decreased series resistance of IOSCs. The best device exhibits a power conversion efficiency of 3.05% after annealing at 150 degrees C.
22.	Scott, Robert A., et al. (author) A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease 2016 In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341 Journal article (peer-reviewed)abstract Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
23.	Shao, Yue, et al. (author) Scalable Synthesis of Photoluminescent Single-Chain Nanoparticles by Electrostatic-Mediated Intramolecular Crosslinking 2022 In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 61:27 Journal article (peer-reviewed)abstract We report the large-scale synthesis of photoluminescent single-chain nanoparticles (SCNPs) by electrostatic-mediated intramolecular crosslinking in a concentrated solution of 40 mg mL−1 by continuous addition of the free radical initiator. Poly(vinyl benzyl chloride) was charged by quaternization with vinyl-imidazolium for the intramolecular crosslinking by using 2,2-dimethoxy-2-phenylacetophenone (DMAP) as the radical initiator. Under the electrostatic repulsion thus interchain isolation, the intrachain crosslinking experiences the transition from coil through pearl-necklace to globular state. The SCNPs demonstrate strong photoluminescence in the visible range when the non-emissive units are confined thereby. Composition and microstructure of the SCNPs are tunable. The photoluminescent tadpole-like Janus SCNP can be used to selectively illuminate interfacial membranes while stabilizing the emulsions.
24.	Stitziel, Nathan O., et al. (author) Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease 2016 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144 Journal article (peer-reviewed)abstract BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
25.	Surendran, Praveen, et al. (author) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension 2016 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161 Journal article (peer-reviewed)abstract High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
26.	Wang, Ying, et al. (author) A tri-level programming-based frequency regulation market equilibrium under cyber attacks 2023 In: Protection and Control of Modern Power Systems. - : Springer Nature. - 2367-2617 .- 2367-0983. ; 8:1 Journal article (peer-reviewed)abstract Owing to their flexibility and rapid response, grid-connected distributed energy resources (DERs) are wielding growing influence in frequency regulation markets (FRMs). Nevertheless, compared with conventional large-scale generators, small-scale DERs are usually weakly shielded by cyber security measures. This offers attackers the opportunity of disrupting the clearing and settlement of FRMs by manipulating the bid information of DERs. In this paper, the frequency regulation market equilibrium is studied considering the dynamic gaming between attackers and defenders, both of which need the knowledge of FRMs for their interventions. Specifically, a tri-level programming model characterizing the attacker–defender–operator (ADO) interdiction problem in FRMs is developed and then analyzed using a column and constraint generation algorithm, thereby achieving market equilibrium representing the defender's best response to the attacker. The defense strategy in the market equilibrium can attenuate the negative influence of cyber attacks upon the FRMs to the maximum extent. Finally, based on the operating rules of the California Independent System Operator, the FRM process considering the ADO interdiction is simulated and the numerical equilibrium results are presented.
27.	Yao, Chen, et al. (author) Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease 2018 In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9 Journal article (peer-reviewed)abstract Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.
28.	Zhu, Mingzhu, et al. (author) L-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein 2014 In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 15:12, s. 23059-23073 Journal article (peer-reviewed)abstract This study was designed to investigate the regulatory role of L-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with L-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L L-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + L-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in L-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that L-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation.

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