Fabrication of long-life quasi-solid-state Na-CO2 battery by formation of Na2C2O4 discharge product

Rechargeable Na-CO2 batteries are promising energy-storage devices due to their high energy density, environmental friendliness, and cost effectiveness. However, the insulating nature and irreversibility of the Na2CO3 discharge product cause large polarization and poor cyclicity. Here, we report a reversible quasi-solid-state Na-CO2 battery that is constructed by the synergistic action of a Co-encapsulated N-doped carbon framework catalyst and gel electrolyte to ensure the formation of a highly reversible Na2C2O4 discharge product. Experiments and density functional theory calculations indicate that the electron-agglomeration effect of Co nanoparticles enhances CO2 adsorption and lowers energy barrier, as well as promotes Na2C2O4 generation. A gel electrolyte containing an imidazole organic cation is used to inhibit the decomposition of the thermodynamically unstable Na2C2O4. The fabricated Na-CO2 battery exhibits a high discharge capacity of 3,094 mAh g^-1, a high-rate performance of 1,777 mAh g^-1 at a current density of 0.5 mA cm^-2, and excellent cycling performance of 366 cycles (2,200 h)

Antioxidant and Antiproliferative Activities of Heated Sterilized Pepsin Hydrolysate Derived from Half-Fin Anchovy (Setipinna taty)

In this paper we studied the antioxidant and antiproliferative activities of the heated pepsin hydrolysate from a marine fish half-fin anchovy (HAHp-H). Furthermore, we compared the chemical profiles including the amino acid composition, the browning intensity, the IR and UV-visible spectra, and the molecular weight distribution between the half-fin anchovy pepsin hydrolysate (HAHp) and HAHp-H. Results showed that heat sterilization on HAHp improved the 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical-scavenging activity and reducing power. In addition, the antiproliferative activities were all increased for HAHp-H on DU-145 human prostate cancer cell line, 1299 human lung cancer cell line and 109 human esophagus cancer cell line. The contents of free amino acid and reducing sugar of HAHp-H were decreased (P < 0.05). However, hydrophobic amino acid residues and the browning intensity of HAHp-H were increased. FT-IR spectroscopy indicated that amide I and amide III bands of HAHp-H were slightly modified, whereas band intensity of amide II was reduced dramatically. Thermal sterilization resulted in the increased fractions of HAHp-H with molecular weight of 3000–5000 Da and below 500 Da. The enhanced antioxidant and antiproliferative activities of HAHp-H might be attributed to the Maillard reaction

A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population

Transformation of human bronchial epithelial cells alters responsiveness to inflammatory cytokines

BACKGROUND: Inflammation is commonly associated with lung tumors. Since inflammatory mediators, including members of the interleukin-6 (IL-6) cytokine family, suppress proliferation of normal epithelial cells, we hypothesized that epithelial cells must develop mechanisms to evade this inhibition during the tumorigenesis. This study compared the cytokine responses of normal epithelial cells to that of premalignant cells. METHODS: Short-term primary cultures of epithelial cells were established from bronchial brushings. Paired sets of brushings were obtained from areas of normal bronchial epithelium and from areas of metaplastic or dysplastic epithelium, or areas of frank endobronchial carcinoma. In 43 paired cultures, the signalling through the signal transducer and activator of transcription (STAT) and extracellular regulated kinase (ERK) pathways and growth regulation by IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), interferon-γ (IFNγ) or epidermal growth factor (EGF) were determined. Inducible expression and function of the leukemia inhibitory factor receptor was assessed by treatment with the histone deacetylase inhibitor depsipeptide. RESULTS: Normal epithelial cells respond strongly to OSM, IFNγ and EGF, and respond moderately to IL-6, and do not exhibit a detectable response to LIF. In preneoplastic cells, the aberrant signaling that was detected most frequently was an elevated activation of ERK, a reduced or increased IL-6 and EGF response, and an increased LIF response. Some of these changes in preneoplastic cell signaling approach those observed in established lung cancer cell lines. Epigenetic control of LIF receptor expression by histone acetylation can account for the gain of LIF responsiveness. OSM and macrophage-derived cytokines suppressed proliferation of normal epithelial cells, but reduced inhibition or even stimulated proliferation was noted for preneoplastic cells. These alterations likely contribute to the supporting effects that inflammation has on lung tumor progression. CONCLUSION: This study indicates that during the earliest stage of premalignant transformation, a modified response to cytokines and EGF is evident. Some of the altered cytokine responses in primary premalignant cells are comparable to those seen in established lung cancer cell lines

Extreme suppression of antiferromagnetic order and critical scaling in a two-dimensional random quantum magnet

Sr_2CuTeO_6 is a square-lattice Néel antiferromagnet with superexchange between first-neighbor S=1/2 Cu spins mediated by plaquette centered Te ions. Substituting Te by W, the affected impurity plaquettes have predominantly second-neighbor interactions, thus causing local magnetic frustration. Here we report a study of Sr_2CuTe_1-xW_xO_6 using neutron diffraction and μSR techniques, showing that the Néel order vanishes already at x=0.025±0.005. We explain this extreme order suppression using a two-dimensional Heisenberg spin model, demonstrating that a W-type impurity induces a deformation of the order parameter that decays with distance as 1/r^2 at temperature T=0. The associated logarithmic singularity leads to loss of order for any x>0. Order for small x>0 and T>0 is induced by weak interplane couplings. In the nonmagnetic phase of Sr_2CuTe_1-x W_x O_6, the μSR relaxation rate exhibits quantum critical scaling with a large dynamic exponent, z≈3, consistent with a random-singlet state.Accepted manuscrip

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk