| 1. |
- Cheng, Q., et al.
(författare)
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Unveiling anneal hardening in dilute Al-doped AlxCoCrFeMnNi (x=0, 0.1) high-entropy alloys
- 2021
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Ingår i: Journal of Materials Science & Technology. - : Elsevier BV. - 1005-0302. ; 91, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- Anneal hardening has been one of the approaches to improve mechanical properties of solid solution alloys with the face-centered cubic (FCC) structure, whereby a considerable strengthening can be attained by annealing of cold-worked alloys below the recrystallization temperature (T-rx). Microscopically, this hardening effect has been ascribed to several mechanisms, i.e. solute segregation to defects (dislocation and stacking fault) and short-range chemical ordering, etc. However, none of these mechanisms can well explain the anneal hardening recently observed in phase-pure and coarse-grained FCC-structured high-entropy alloys (HEAs). Here we report the observations, using high-resolution electron channeling contrast imaging and transmission electron microscopy, of profuse and stable dislocation substructures in a cold-rolled CoCrFeMnNi HEA subject to an annealing below T-rx. The dislocation substructures are observed to be thermally stable up to T-rx, which could arise from the chemical complexity of the high-entropy system where certain elemental diffusion retardation occurs. The microstructure feature is markedly different from that of conventional dilute solid solution alloys, in which dislocation substructures gradually vanish by recovery during annealing, leading to a strength drop. Furthermore, dilute addition of 2 at.% Al leads to a reduction in both microhardness and yield strength of the cold-rolled and subsequently annealed (<= 500 degrees C) HEA. This Al induced softening effect, could be associated with the anisotropic formation of dislocation substructure, resulting from enhanced dislocation planar slip due to glide plane softening effect. These findings suggest that the strength of HEAs can be tailored through the anneal hardening effect from dislocation substructure strengthening.
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| 2. |
- Kirchhoff, Tomas, et al.
(författare)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 3. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 4. |
- Stevens, Kristen N, et al.
(författare)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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| 5. |
- Yoshiji, Satoshi, et al.
(författare)
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Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
- 2023
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5, s. 248-264
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Tidskriftsartikel (refereegranskat)abstract
- How obesity contributes to COVID-19 severity is not fully understood. In this study, Yoshiji et al. found that the plasma protein nephronectin partially mediates the effect of obesity on the risk of COVID-19 severity using a two-step Mendelian randomization approach and omics analyses. Obesity is a major risk factor for Coronavirus disease (COVID-19) severity; however, the mechanisms underlying this relationship are not fully understood. As obesity influences the plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity in humans. Here, we screened 4,907 plasma proteins to identify proteins influenced by body mass index using Mendelian randomization. This yielded 1,216 proteins, whose effect on COVID-19 severity was assessed, again using Mendelian randomization. We found that an s.d. increase in nephronectin (NPNT) was associated with increased odds of critically ill COVID-19 (OR = 1.71, P = 1.63 x 10(-10)). The effect was driven by an NPNT splice isoform. Mediation analyses supported NPNT as a mediator. In single-cell RNA-sequencing, NPNT was expressed in alveolar cells and fibroblasts of the lung in individuals who died of COVID-19. Finally, decreasing body fat mass and increasing fat-free mass were found to lower NPNT levels. These findings provide actionable insights into how obesity influences COVID-19 severity.
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| 6. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 7. |
- Chang, Yanhai, et al.
(författare)
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Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling
- 2017
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Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 91, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Mycotoxin T-2 exerts a causative role in Kashin-Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1ß in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1ß in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1ß were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1ß antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1β further aggravated cell damage in response to T-2. Additionally, cessation of IL-1β rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1β stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/β-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1β inhibition, but further enhanced following IL-1β precondition. Importantly, blocking this pathway by transfection with β-catenin alleviated the adverse roles of IL-1β on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy.
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| 8. |
- Cheng, Q., et al.
(författare)
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Solid solution softening in a Aloi CoCrFeMnNi high-entropy alloy
- 2020
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Ingår i: Scripta Materialia. - : Elsevier BV. - 1359-6462 .- 1872-8456. ; 186, s. 63-68
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Tidskriftsartikel (refereegranskat)abstract
- Solute effects on high-entropy alloys of equiatomic proportions are scientifically intriguing because there is no such well-defined "solute" and "solvent" atoms compared to those of conventional single principal element alloys. To date, most of the face-centered cubic alloys exhibit solid solution strengthening rather than softening due to the interactions between dislocations and solute atoms. Here, we present the careful experimental measurements and demonstrate solid solution softening, albeit weak, in a single phase CoCrFeMnNi through the minor addition of 2. at.% Al. This softening effect is mostly related to the decreased Peierl's stress by Al addition.
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| 9. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 10. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 11. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 12. |
- Jiang, Xiangang, et al.
(författare)
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Internal erosion of debris-flow deposits triggered by seepage
- 2023
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Ingår i: Engineering Geology. - : Elsevier BV. - 0013-7952 .- 1872-6917. ; 314, s. 107015-
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Tidskriftsartikel (refereegranskat)abstract
- Debris flows can be triggered by runoffs at considerably steep natural channels and streams. Specifically, runoffgenerated debris-flow deposits are loose mixtures, comprising coarse and fine particles. Owing to seeping water, these fine particles are eroded and transported through the skeleton formed by the coarse particles. Such erosion can modify the porosity of deposits and influence their mechanical characteristics, which can be non-negligible for geotechnical and geological engineering. In this study, seven groups of seepage tests on gravel-sand-clay mixtures with different coarse particle content proportions (48%, 52%, 60%, 70%, 80%, 90%, and 100%) were conducted to investigate the erosion characteristics of debris-flow deposits triggered by seepage flows. In particular, concentrated leak erosion, internal instability erosion, and piping were noted in the soil with a coarse particle content of 48%-80%. Further, when the coarse particle content exceeds 80%, the soil does not disintegrate. A model coupling seepage and internal erosion was also developed to characterise internal erosion. For this model, mass conservation equations were reformulated for different types of internal erosion, based on the assumptions for the pore channel erosion of suspended materials and general erosion. Moreover, an equation based on the internal erosion rate, considering the pore size distribution and hydraulic gradient, was firstly introduced for concentrated leak and internal instability erosion. This equation could efficiently evaluate the mass of particles eroded from the soil. Lastly, the model was calibrated based on experimental data; the corresponding results are discussed herein.
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| 13. |
- Lei, Xiaoqin, et al.
(författare)
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A generalized interpolation material point method for modelling coupled thermo-hydro-mechanical problems
- 2021
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Ingår i: Computer Methods in Applied Mechanics and Engineering. - : Elsevier BV. - 0045-7825. ; 386
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Tidskriftsartikel (refereegranskat)abstract
- This paper proposes a Generalized Interpolation Material Point Method (GIMP) for modelling coupled thermo-hydro-mechanical (THM) processes within unsaturated porous media. The governing equations for the coupled thermo-hydro-mechanical problems are derived based on the conservation laws of mass, momentum and energy, and are discretized within the framework of the explicit three-phase single-point GIMP. The proposed THM-coupled GIMP is validated against available analytical solutions and FEM-based numerical solutions, and is used for simulating a climate-driven slope failure process involving both temperature variation and rainfall infiltration. The proposed THM-coupled GIMP is proved to be capable to capture the fully coupled thermo-hydro-mechanical process within unsaturated porous media associated with large deformations.
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| 14. |
- Li, Xiaoqing, et al.
(författare)
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Antihyperuricemic Effect of Green Alga Ulva lactuca Ulvan through Regulating Urate Transporters
- 2021
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 69:38, s. 11225-11235
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Tidskriftsartikel (refereegranskat)abstract
- A novel polysaccharide from Ulva lactuca (ULP) was purified using a Sepharose CL-4B column. Fourier transform infrared spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy were employed to analyze the structure of ULP. It consisted of rhamnose (Rha), glucuronic acid (GluA), galactose (Gal), and xylose (Xyl) at a molar ratio of 32.75:22.83:1.07:6.46 with the molecular weight of 2.24 x 10(5) Da. The four major glycosidic residues found in ULP were -> 2,3)-alpha-L-Rhap-(1 ->, -> 4)-beta-D-GlcpA-(1 ->, -> 2,6)-beta-D-Galp-(1 ->, and -> 4)-beta-D-Xylp-(1 ->. The antihyperuricemic activity of ULP was exhibited by detecting related biochemical indexes, urate transporter gene expressions, renal histopathology, and intestinal microbiota shifts. ULP obviously decreased the levels of serum uric acid (UA), blood urea nitrogen, and creatinine, while inhibited serum and hepatic xanthine oxidase activities as well as improved renal injury in hyperuricemic mice. Furthermore, the upregulation of UA excretion genes ABCG2/OAT1 and downregulation of UA resorption genes URAT1 and GLUT9 were detected. In addition, ULP exerted its antihyperuricemic effect through regulating the intestinal microbiome, characterized by elevating the helpful microbial abundance, meanwhile declining the harmful bacterial abundance and restoring the gut microbiome homeostasis. This study demonstrates the antihyperuricemic activity of ULP and its potential effect for the treatment of hyperuricemia-related diseases.
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| 15. |
- Martrat, Griselda, et al.
(författare)
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Exploring the link between MORF4L1 and risk of breast cancer
- 2011
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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| 16. |
- Mu, Cuicui, et al.
(författare)
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Ecosystem CO2 Exchange and Its Economic Implications in Northern Permafrost Regions in the 21st Century
- 2023
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 37:11
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming increases carbon assimilation by plant growth and also accelerates permafrost CO2 emissions; however, the overall ecosystem CO2 balance in permafrost regions and its economic impacts remain largely unknown. Here we synthesize in situ measurements of net ecosystem CO2 exchange to assess current and future carbon budgets across the northern permafrost regions using the random forest model and calculate their economic implications under the Shared Socio-economic Pathways (SSPs) based on the PAGE-ICE model. We estimate a contemporary CO2 emission of 1,539 Tg C during the nongrowing season and CO2 uptake of 2,330 Tg C during the growing season, respectively. Air temperature and precipitation exert the most control over the net ecosystem exchange in the nongrowing season, while leaf area index plays a more important role in the growing season. This region will probably shift to a carbon source after 2,057 under SSP5-8.5, with a net emission of 17 Pg C during 2057–2100. The net economic benefits of CO2 budget will be $4.5, $5.0, and $2.9 trillion under SSP1-2.6, SSP2-4.5, and SSP5-8.5, respectively. Our results imply that a high-emission pathway will greatly reduce the economic benefit of carbon assimilation in northern permafrost regions.
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| 17. |
- Qin, Gang, et al.
(författare)
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A novel face-centered-cubic high-entropy alloy strengthened by nanoscale precipitates
- 2019
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Ingår i: Scripta Materialia. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1359-6462 .- 1872-8456. ; 172, s. 51-55
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Tidskriftsartikel (refereegranskat)abstract
- A new single-phase face-centered-cubic (FCC) Co9Cr7Cu36Mn25Ni23 [atomic percent, similar hereinafter] high-entropy alloy (HEA) was prepared by arc melting. A uniform distribution of nanometer-sized precipitates was achieved. The tensile yield strength, ultimate tensile strength, and elongation were 401 MPa, 700 MPa, and 36%, respectively. The energy-dispersive spectrometer results showed that the nano-precipitates were rich in Co and Cr elements. Moreover, the crystal-forming behavior and the nanoscale-precipitates-forming mechanism were revealed. Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 18. |
- Qin, Gang, et al.
(författare)
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An as-cast high-entropy alloy with remarkable mechanical properties strengthened by nanometer precipitates
- 2020
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Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 12:6, s. 3965-3976
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Tidskriftsartikel (refereegranskat)abstract
- High-entropy alloys (HEAs) with good ductility and high strength are usually prepared by a combination of forging and heat-treatment processes. In comparison, the as-cast HEAs typically do not reach strengths similar to those of HEAs produced by the forging and heat-treatment processes. Here we report a novel equiatomic-ratio CoCrCuMnNi HEA prepared by vacuum arc melting. We observe that this HEA has excellent mechanical properties, i.e., a yield strength of 458 MPa, and an ultimate tensile strength of 742 MPa with an elongation of 40%. Many nanometer precipitates (5-50 nm in size) and domains (5-10 nm in size) are found in the inter-dendrite and dendrite zones of the produced HEA, which is the key factor for its excellent mechanical properties. The enthalpy of mixing between Cu and Mn, Cr, Co, or Ni is higher than those of mixing between any two of Cr, Co, Ni and Mn, which leads to the separation of Cu from the CoCrCuMnNi HEA. Furthermore, we reveal the nanoscale-precipitate-phase-forming mechanism in the proposed HEA.
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| 19. |
- Qin, Gang, et al.
(författare)
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Experimental and theoretical investigations on the phase stability and mechanical properties of Cr7Mn25Co9Ni23Cu36 high-entropy alloy
- 2021
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanisms of phase formation and their influence on the mechanical behavior is crucial for materials used in structural applications. Here, the phase decomposition under heat treatment in the Cr7Mn25Co9Ni23Cu36 (atomic percentage) high-entropy alloy and how secondary phases formed affect its tensile mechanical response are reported. The microstructural analysis shows that heat treatment at 800 degrees C /2 h and 600 degrees C /8 h led to the formation of sigma phase, but the sigma phase was not observed for 2 h heat treatment at 600 degrees C and below. The experimentally observed thermal stability and phases are compared to the calculated phase diagram and rationalized by recourse to thermodynamics and kinetics. The mechanism of phase decomposition is discussed based on ab initio calculations, indicating that decomposition into two solid solution phases is energetically preferred over a single solid solution phase with nominal composition.
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| 20. |
- Qu, Muchao, et al.
(författare)
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Mechanical and electrical properties of carbon nanotube/epoxy/glass-fiber composites intended for nondestructive testing
- 2023
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Ingår i: Polymers for Advanced Technologies. - : Wiley. - 1042-7147 .- 1099-1581. ; 34:8, s. 2554-2563
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Tidskriftsartikel (refereegranskat)abstract
- In this study, ternary polymer composites sheets comprising glass fiber (GF) reinforced epoxy with various fractions of carbon nanotubes (CNT) were manufactured using hot-pressing technology. A multiscale morphology analysis was presented using scanning electron microscopy. The thermal behavior of the glass fiber reinforced polymer (GFRP) was investigated using thermogravimetric analysis, DSC, and DMA, which indicated an application temperature up to 71°C for the composites. Mechanical uniaxial stretching and three-points bending tests showed that the addition of 0.1–0.2 wt% CNT decreased the dissipated energy of the specimen by 50% and increased the Young's modulus by more than 100%. During all stretching and bending measurements, the relative change in electrical resistance (RCR) was recorded as function of strain, revealing a relationship between the electrical signal and the applied deformation of the GFRP. Finally, the standard equation for fitting RCR versus strain was optimized, reducing the number of fitting parameters from five to three. The electrical and mechanical properties of the CNT/GF/epoxy composites show that they are suitable sensoring materials for wind-turbine blades and other glass-fiber reinforced epoxy constructions, especially for nondestructive testing.
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| 21. |
- Spurdle, Amanda B., et al.
(författare)
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Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
- 2011
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 20:5, s. 1032-1038
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR.
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| 22. |
- Sun, Zhengyi, 1982-, et al.
(författare)
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Buffer-enhanced electron injection in organic light-emitting devices with copper cathode
- 2013
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Ingår i: Organic electronics. - Amsterdam : Elsevier. - 1566-1199 .- 1878-5530. ; 14:2, s. 511-515
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Tidskriftsartikel (refereegranskat)abstract
- We explore in this work the use of Cu as a cathode material in organic light-emitting devices (OLEDs) and find a dual electron–injection enhancement mechanism derived from the LiF layer. Different from what observed previously in Ag- and Au-cathode devices, the LiF buffer layer in the Cu-cathode OLEDs starts to play its role in performance improvement when it is much thinner than 3 nm, the optimal value of buffer thickness, and in the case of optimal thickness, the device exhibits excellent performance comparable to conventional Al-cathode device. The phenomenon observed is ascribed to enhanced electron injection as a result of combined effect of interfacial reaction and tunneling barrier reduction mechanism: while chemical reaction plays a key role at the very beginning of interface formation, tunneling dominates in the subsequent stage leading to the tremendous improvement of the characteristics.
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| 23. |
- Walker, Logan C, et al.
(författare)
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Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers.
- 2010
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X .- 1465-5411. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies.
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| 24. |
- Wang, Xiaoqing, et al.
(författare)
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Inhibiting the aberrant activation of Wnt/β-catenin signaling by selenium supplementation ameliorates deoxynivalenol-induced toxicity and catabolism in chondrocytes
- 2020
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Ingår i: Journal of Cellular Physiology. - : Wiley-Blackwell. - 0021-9541 .- 1097-4652. ; 235:5, s. 4434-4442
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Tidskriftsartikel (refereegranskat)abstract
- Kashin-Beck disease (KBD) is an endemic degenerative osteoarticular disorder associated with physical disability and a heavy economic burden. Contamination by mycotoxin deoxynivalenol (DON) and selenium deficiency have been proposed to be key etiological factors for KBD, and can work together to aggravate the progression of KBD. Nevertheless, the mechanism of DON in KBD remains elusive. In the present study, exposure to DON dose-dependently suppressed cell viability and expression of pro-proliferation marker PCNA in human chondrocytes, whereas it enhanced lactate dehydrogenase release, cell apoptosis, and caspase-3/9 activity. In addition, DON incubation shifted metabolism homeostasis towards catabolism by suppressing the transcription of collagen II and aggrecan, and the production of sulphated glycosaminoglycans and TIMP-1, while increasing matrix metalloproteinase levels (MMP-1 and MMP-13). Mechanistically, DON exposure induced the activation of Wnt/β-catenin signaling. Intriguingly, blocking this pathway reversed the adverse effects of DON on cytotoxic damage and metabolism disruption to catabolism. Notably, supplementation with selenium reduced DON-induced activation of the Wnt/β-catenin pathway. Moreover, selenium addition abrogated cytotoxic injury and excessive pro-catabolic gene expression in chondrocytes upon DON conditions. These findings confirm that DON may facilitate the development of KBD by inducing cell injury, inhibiting matrix synthesis, and increasing cellular catabolism by activating the Wnt/β-catenin signaling, which were partially reversed by selenium supplementation. Thus, the current study may presents a new viewpoint for how selenium supplementation ameliorates the development of KBD by inhibiting DON-induced cytotoxic injury and metabolism imbalance in chondrocytes.
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| 25. |
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