| 61. |
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| 62. |
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| 63. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 64. |
- Shen, Weixing, et al.
(författare)
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Protective effects of Wang-Bi tablet on bone destruction in collagen-induced arthritis by regulating osteoclast-osteoblast functions.
- 2019
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Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 238
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Tidskriftsartikel (refereegranskat)abstract
- ETHNOPHARMACOLOGICAL RELEVANCE: Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear.AIM OF STUDY: The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism.MATERIALS AND METHODS: DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37 g/kg/d) or WB at a lower (1.11 g/kg/d, WBL) or higher dose of (3.33 g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined.RESULTS: Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice.CONCLUSION: Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions.
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| 65. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 66. |
- Sun, Xin, et al.
(författare)
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Reducing supply risk of critical materials for clean energy via foreign direct investment
- 2024
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Ingår i: Nature Sustainability. - : Springer Nature. - 2398-9629. ; 7:5, s. 672-681
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Tidskriftsartikel (refereegranskat)abstract
- Existing research on the security of the supply of critical materials for clean energy generally aggregates information at the country level, a practice that obscures the extensive role of foreign direct investment (FDI) in the production of critical materials. FDI refers to an ownership stake in a company or project by an overseas investor. Here we establish a database for global mining of lithium, cobalt, nickel and platinum at company level, covering 240 countries and regions. We show that 47% of lithium, 71% of cobalt, 41% of nickel and 34% of platinum mined in 2019 were under FDI. We then explore how FDI may affect supply risks by proposing a supply risk index that allocates production of the critical materials to the country of origin of investors instead of the country where production is located. We present upper and lower bounds of the supply risk index that reflect scenarios where either all investors or only state investors prioritize the home-country demand, respectively. This study presents an approach for assessing the national supply risks of critical materials, considering the geographical allocation of FDI.
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| 67. |
- Wang, Xinqi, et al.
(författare)
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Levels, distribution, sources and children health risk of PAHs in residential dust : A multi-city study in China
- 2023
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 862
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polycyclic aromatic hydrocarbons (PAHs) are typical residential pollutants mainly from biofuel combustion that impose inevitable risk to children. The PAHs in residential dust is universal in most Chinese households with an obvious public health concern.Methods: In this observational study, a total of 235 residential dust samples from 8 Chinese cities (Panjin, Shijiazhuang, Lanzhou, Luoyang, Xi'an, Wuxi, Mianyang, and Shenzhen) were collected from April 2018 to March 2019, which were extracted and analyzed for 16 priority PAHs by HPLC/FD-UV. Diagnostic ratios, hierarchical clustering analysis and principal component analysis were applied simultaneously for source apportionments. Incremental lifetime cancer risk was employed to estimate children's health risks based on the assumed exposure scenarios. Spearman correlation, Mann-Whitney U test, Kruskal-Wallis H test and Partial Least Squares were used to screen the factors affecting the concentration of PAHs in residential dust.Results: The median concentration of ∑16PAHs in residential dust from 8 cities was 44.11 μg/g (0.04 - 355.79 μg/g). ∑16PAHs were found both higher in dust samples in heating season and from downwind households only in Mianyang (p < 0.05). The leading two sources of PAHs were combustion processes and automobile exhaust emissions based on four principal components that accounted for 74.29 % of the total variance. Indoor air environmental factors, household characteristics, and residents' behavioral lifestyles may be the influencing factors of residential dust PAHs. The carcinogenic risk of children aged 0 - 5 years, under the moderate exposure level of PAHs in residential dust, exceeded the acceptable level (10−5 - 10−4 for dermal contact and 10−6 - 10−5 for ingestion).Conclusions: There was serious PAHs pollution in residential dust under actual living conditions in eight cities across China. More evidence-based measures were needed to control PAHs pollution to safeguard children's health according to appointed sources and influencing factors in residential dust.
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| 68. |
- Wang, Zhigang, et al.
(författare)
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Decreased Splenic CD4(+) T-Lymphocytes in Apolipoprotein M Gene Deficient Mice
- 2015
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Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- Spleen T-lymphocytes, especially CD4(+) T-cells, have been demonstrated to be involved in broad immunomodulation and host-defense activity in vivo. Apolipoprotein M gene (apoM) may have an important role in the regulation of immunoprocess and inflammation, which could be hypothesized to the apoM containing sphingosine-1-phosphate (S1P). In the present study we demonstrate that the splenic CD4(+) T-lymphocytes were obviously decreased in the apoM gene deficient (apoM(-/-)) mice compared to the wild type (apoM(+/+)). Moreover, these mice were treated with lipopolysaccharide (LPS) and it was found that even more pronounced decreasing CD4(+) T-lymphocytes occurred in the spleen compared to the apoM(+/+) mice. The similar phenomena were found in the ratio of CD4(+)/CD8(+) T-lymphocytes. After administration of LPS, the hepatic mRNA levels of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 (MCP-1) were markedly increased; however, there were no statistical differences observed between apoM(+/+) mice and apoM(-/-) mice. The present study demonstrated that apoM might facilitate the maintenance of CD4(+) T-lymphocytes or could modify the T-lymphocytes subgroups in murine spleen, which may further explore the importance of apoM in the regulation of the host immunomodulation, although the detailed mechanism needs continuing investigation.
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| 69. |
- Wang, Zhaofeng, et al.
(författare)
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Phylogeographical analyses of domestic and wild yaks based on mitochondrial DNA : new data and reappraisal
- 2010
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 37:12, s. 2332-2344
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Tidskriftsartikel (refereegranskat)abstract
- Aim We aimed to examine the phylogeographical structure and demographic history of domestic and wild yaks (Bos grunniens) based on a wide range of samples and complete mitochondrial genomic sequences. Location The Qinghai-Tibetan Plateau (QTP) of western China. Methods All available D-loop sequences for 405 domesticated yaks and 47 wild yaks were examined, including new sequences from 96 domestic and 34 wild yaks. We further sequenced the complete mitochondrial genomes of 48 domesticated and 21 wild yaks. Phylogeographical analyses were performed using the mitochondrial D-loop and the total genome datasets. Results We recovered a total of 123 haplotypes based on the D-loop sequences in wild and domestic yaks. Phylogenetic analyses of this dataset and the mitochondrial genome data suggested three well-supported and divergent lineages. Two lineages with six D-loop haplogroups were recovered for all morphological breeds of domestic yaks across their distributions in the QTP, while one more lineage and more endemic haplogroups or haplotypes were found for wild yaks. Based on the mitochondrial genome data, the divergences of the three lineages were estimated to have occurred around 420,000 and 580,000 years ago, consistent with the geological records of two large glaciation events experienced in the QTP. Main conclusions There are distinct phylogeographical differences between wild and domestic yaks. However, there is no apparent geographical correlation between identified haplogroups and distributions of domestic yaks. Three differentiated lineages of yaks probably evolved allopatrically in different regions during the Pleistocene glaciation events, then reunited into a single gene pool during post-glacial population expansion and migrations before the start of the domestication of yaks in the Holocene.
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| 70. |
- Yu, Tao, 1988, et al.
(författare)
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Metabolic reconfiguration enables synthetic reductive metabolism in yeast
- 2022
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:11, s. 1551-1559
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Tidskriftsartikel (refereegranskat)abstract
- Cell proliferation requires the integration of catabolic processes to provide energy, redox power and biosynthetic precursors. Here we show how the combination of rational design, metabolic rewiring and recombinant expression enables the establishment of a decarboxylation cycle in the yeast cytoplasm. This metabolic cycle can support growth by supplying energy and increased provision of NADPH or NADH in the cytosol, which can support the production of highly reduced chemicals such as glycerol, succinate and free fatty acids. With this approach, free fatty acid yield reached 40% of theoretical yield, which is the highest yield reported for Saccharomyces cerevisiae to our knowledge. This study reports the implementation of a synthetic decarboxylation cycle in the yeast cytosol, and its application in achieving high yields of valuable chemicals in cell factories. Our study also shows that, despite extensive regulation of catabolism in yeast, it is possible to rewire the energy metabolism, illustrating the power of biodesign.
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