| 1. |
- Aglago, Elom K., et al.
(författare)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 2. |
- Carreras-Torres, Robert, et al.
(författare)
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Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 315-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.IMPACT: These findings can guide potential prevention treatments.
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| 3. |
- Jiang, Lan, et al.
(författare)
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Heparin mimetics as potential intervention for COVID-19 and their bio-manufacturing
- 2023
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Ingår i: SYNTHETIC AND SYSTEMS BIOTECHNOLOGY. - : KEAI PUBLISHING LTD. - 2405-805X. ; 8:1, s. 11-19
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Forskningsöversikt (refereegranskat)abstract
- The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy. Moreover, after more than 2 years, many populations are still under pressure of infection. Thus, a broader perspective in developing antiviral strategies is still of great importance. Inspired by the observed multiple benefits of heparin in the treatment of thrombosis, the potential of low molecular weight heparin (LMWH) for the treatment of COVID-19 have been explored. Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients, accordingly reducing lethality. Furthermore, several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection. These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates. In this review, we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection, focusing on the perspectives of developing heparin mimetics via chemical synthesis, chemoenzymatic synthesis, and bioengineered production by microbial cell factories. The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.
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| 4. |
- Li, Dongqing, et al.
(författare)
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miR-19a/b and miR-20a promote wound healing by regulating the inflammatory response of keratinocytes
- 2021
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 141:3, s. 659-671
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Tidskriftsartikel (refereegranskat)abstract
- Persistent and impaired inflammation impedes tissue healing and is characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. Here we show that in human wound-edge keratinocytes, the expression of miR-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, is upregulated during wound repair. However, their levels are lower in chronic ulcers than acute wounds at the proliferative phase. Conditional knockout of miR-17∼92 in keratinocytes as well as injection of miR-19a/b and miR-20a antisense inhibitors into wound-edges enhanced inflammation and delayed wound closure in mice. In contrast, conditional overexpression of the miR-17∼92 cluster or miR-19b alone in mice keratinocytes accelerated wound closure in vivo. Mechanistically, miR-19a/b and miR-20a decreased TLR3-mediated NF-κB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines/cytokines by keratinocytes. Thus, as crucial regulators of wound inflammation, lack of miR-19a/b and miR-20a may contribute to sustained inflammation and impaired healing in chronic wounds. In line with this, we show that a combinatory treatment with miR-19b and miR-20a improved wound healing in a mouse model of type 2 diabetes.
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| 5. |
- Tian, Yu, et al.
(författare)
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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
- 2024
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130:10, s. 1687-1696
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Tidskriftsartikel (refereegranskat)abstract
- Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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| 6. |
- Tian, Yu, et al.
(författare)
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Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:8, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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| 7. |
- Tsilidis, Konstantinos K., et al.
(författare)
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Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent : a Mendelian randomization study
- 2021
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:6, s. 1490-1502
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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| 8. |
- Xia, Zhiyu, et al.
(författare)
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Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.
- 2020
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:10, s. 3563-3573
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ).CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.
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| 9. |
- Zhang, Tianji, et al.
(författare)
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Interacting polymer-modification enzymes in heparan sulfate biosynthesis
- 2023
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 299
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Tidskriftsartikel (refereegranskat)abstract
- Glucuronyl 5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) into L-iduronic acid (IdoA) units, through a mechanism involving reversible abstraction of a proton at C5 of hexuronic acid residues. Incubations of a [4GlcA beta 1-4GlcNSO3 alpha 1-]n precursor substrate with recombinant enzymes in a D2O/H2O medium enabled an isotope exchange approach to the assessment of functional interactions of Hsepi with hexuronyl 2-O-sulfotrans-ferase (Hs2st) and glucosaminyl 6-O-sulfotransferase (Hs6st), both involved in the final polymer-modification steps. Enzyme complexes were supported by computational modeling and homogeneous time resolved fluores-cence. GlcA and IdoA D/H ratios related to product composition revealed kinetic isotope effects that were interpreted in terms of efficiency of the coupled epimerase and sulfotransferase reactions. Evidence for a func-tional Hsepi/Hs6st complex was provided by selective incorporation of D atoms into GlcA units adjacent to 6-O -sulfated glucosamine residues. The inability to achieve simultaneous 2-O-and 6-O-sulfation in vitro supported topologically separated reactions in the cell. These findings provide novel insight into the roles of enzyme in-teractions in heparan sulfate biosynthesis.
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| 10. |
- Gu, Yeqing, et al.
(författare)
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Consumption of ultraprocessed food and development of chronic kidney disease : the Tianjin Chronic Low-Grade Systemic Inflammation and Health and UK Biobank Cohort Studies
- 2023
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 117:2, s. 373-382
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany ultraprocessed food (UPF)-derived by-products may play a role in the development of chronic kidney disease (CKD). Although several studies have assessed the association of UPFs with kidney function decline or CKD in various countries, no evidence has been shown in China and the United Kingdom.ObjectivesThis study aims to evaluate the association between UPF consumption and risk of CKD in 2 large cohort studies from China and the United Kingdom.MethodsIn total, 23,775 and 102,332 participants without baseline CKD were enrolled in the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) and UK Biobank cohort studies, respectively. Information on UPF consumption was obtained from a validated food frequency questionnaire in the TCLSIH and 24-h dietary recalls in the UK Biobank cohort. CKD was defined as an estimated glomerular filtration rate of ResultsAfter a median follow-up of 4.0 and 10.1 y, the incidence rates of CKD were around 1.1% and 1.7% in the TCLSIH and UK Biobank cohorts, respectively. The multivariable hazard ratio [95% confidence interval] of CKD across increasing quartiles (quartiles 1–4) of UPF consumption were 1 (reference), 1.24 (0.89, 1.72), 1.30 (0.91, 1.87), and 1.58 (1.07, 2.34) (P for trend = 0.02) in the TCLSIH cohort and 1 (reference), 1.14 (1.00, 1.31), 1.16 (1.01, 1.33), and 1.25 (1.09, 1.43) (P for trend < 0.01) in the UK Biobank cohort, respectively.ConclusionsOur finding indicated that higher UPF consumption is associated with a higher risk of CKD. Moreover, restricting UPF consumption may potentially benefit the prevention of CKD. Further clinical trials are required to clarify the causality.
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| 11. |
- McNabb, Sarah, et al.
(författare)
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Meta-analysis of 16 studies of the association of alcohol with colorectal cancer
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:3, s. 861-873
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (<= 1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
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| 12. |
- Yu, Mingjia, et al.
(författare)
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Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins : An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 7
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Forskningsöversikt (refereegranskat)abstract
- Owing to the high mortality and the spread rate, the infectious disease caused by SARS-CoV-2 has become a major threat to public health and social economy, leading to over 70 million infections and 1. 6 million deaths to date. Since there are currently no effective therapeutic or widely available vaccines, it is of urgent need to look for new strategies for the treatment of SARS-CoV-2 infection diseases. Binding of a viral protein onto cell surface heparan sulfate (HS) is generally the first step in a cascade of interaction that is required for viral entry and the initiation of infection. Meanwhile, interactions of selectins and cytokines (e.g., IL-6 and TNF-α) with HS expressed on endothelial cells are crucial in controlling the recruitment of immune cells during inflammation. Thus, structurally defined heparin/HS and their mimetics might serve as potential drugs by competing with cell surface HS for the prevention of viral adhesion and modulation of inflammatory reaction. In this review, we will elaborate coronavirus invasion mechanisms and summarize the latest advances in HS-protein interactions, especially proteins relevant to the process of coronavirus infection and subsequent inflammation. Experimental and computational techniques involved will be emphasized.
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| 13. |
- Zhang, Rui, et al.
(författare)
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Selective binding of heparin oligosaccharides in a magnetic thermoresponsive molecularly imprinted polymer
- 2019
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Ingår i: Talanta. - : Elsevier. - 0039-9140 .- 1873-3573. ; 201, s. 441-449
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Forskningsöversikt (refereegranskat)abstract
- Heparin is a highly sulfated polysaccharide, applied in clinic for treatment of thrombotic diseases. The biological activity is closely related to its molecular structure e.g. compositions of disaccharides and oligosaccharides units. The classical method to isolate the oligosaccharides after depolymerization by heparinases or nitrous acid I s by size exclusion chromatography which is a time-consuming process. In this study, we explored the possibility for rapid separation of oligosaccharides using a novel polymer material. The magnetic thermoresponsive molecularly imprinted polymers (MIPs) were synthesized using heparin disaccharide as a template, AEM, NIPAAm, and AAm as functional monomer, and MBAA as crosslinker by surface radical polymerization in an aqueous media. Incubation of the MIP with hepairn oligosaccharides demonstrated specific binding to the template molecule. This binding to the targeted molecule was affected by reaction temperature with regard to binding capacity and specificity. The recognition specificity and selectivity can be modulated by varying the compositions of multifunctional monomers. The pseudo-second-order kinetic model and Langmuir isotherm model provide the best fit to the equilibrium adsorption of heparin disaccharides by MIPs. The results suggest that the new material can be used for rapid separation of di- and tetra-saccharides of heparin, which can also be adapted to the applications for isolation of oligosaccharides from other polysaccharides, e.g. heparan sulfate and chondoriting sulfate.
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| 14. |
- Zhang, Shunming, et al.
(författare)
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Added sugar intake and its forms and sources in relation to risk of non-alcoholic fatty liver disease : results from the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study
- 2023
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 129:12, s. 2094-2101
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid vs. solid), and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15,538 participants, free of NAFLD, other liver diseases, cardiovascular disease, cancer, or diabetes at baseline (2013-2018 years). Added sugar intake was estimated from a validated 100-item food frequency questionnaire. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for NAFLD risk with added sugar intake. During a median follow-up of 4.2 years, 3,476 incident NAFLD cases were documented. After adjusting for age, sex, body mass index and its change from baseline to follow-up, lifestyle factors, personal and family medical history, and overall diet quality, the multivariable HRs (95% CIs) of NAFLD risk were 1.18 (1.06, 1.32) for total added sugars, 1.20 (1.08, 1.33) for liquid added sugars, and 0.96 (0.86, 1.07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
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| 15. |
- Zhang, Tianji, et al.
(författare)
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Characterization of epimerization and composition of heparin and dalteparin using a UHPLC-ESI-MS/MS method
- 2019
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Ingår i: Carbohydrate Polymers. - : ELSEVIER SCI LTD. - 0144-8617 .- 1879-1344. ; 203, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Heparin is a significant anticoagulant that has been used in clinic over decades. Although numerous efforts have been made to characterize the molecular structure of heparin and its derivatives for safety of the medicine, technical barriers still exist because of their structural complexity. In this study, we have established a method capable to evaluate both the epimerization and composition of heparin and dalteparin by a UHPLC-HILIC/WAXMS/MS approach. Ten major disaccharide building blocks retaining the epimerization configuration of parental heparin chains were generated and well separated, 9 of which were unambiguously identified. Isomer identifications were achieved through high-resolution tandem mass spectrometry analysis with reference to elaborately prepared standards. The method was successfully applied for the sameness study of generic dalteparins in combination with an isotopic labelling procedure. We believe this robust method maybe adapted to quality control in pharmaceutical production of heparin and LMWHs.
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| 16. |
- Zhang, Tianji, et al.
(författare)
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Glycosaminoglycans in biological samples : towards identification of novel biomarkers
- 2020
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier BV. - 0165-9936 .- 1879-3142. ; 122
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Forskningsöversikt (refereegranskat)abstract
- Glycosaminoglycans (GAGs) are unbranched polyanionic polysaccharides involved in a wide spectrum of biological activities. Accumulation and/or structural alteration of GAGs in biological samples have been found correlated with diseases, making these molecules potential biomarkers for the diagnosis of these diseases and monitoring treatment effects. Detection and structural characterization of GAGs in biological samples have been challenging mainly due to their low abundance, structural complexity and heterogeneity. It is highly demanding to develop robust and reliable methodologies for structural characterization and quantification of GAGs, not only for research purposes, but most importantly for pharmaceutical and potential clinical applications, including pharmacokinetic studies for GAGs based drugs and identification of novel biomarkers. In this review, we have collected currently available techniques for detection and analysis of GAGs in biological samples, advantages and drawbacks of these techniques are discussed. Specially, perspectives of the developing methods for GAGs are reviewed.
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| 17. |
- Zhang, Tianji, et al.
(författare)
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In-depth characterization of 1,4-butanediol diglycidyl ether substituted hyaluronic acid hydrogels
- 2023
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 307
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Tidskriftsartikel (refereegranskat)abstract
- BDDE substituted HA hydrogels remain the most commonly used HA product in the biomedical field. The physical and biochemical properties of the hydrogels are dependent on the degree of modification and substitution patterns/positions, thus, characterizing their fine structure is of great importance for quality assurance. In this study, we developed novel LC-MS methods for accurate determination of MoD as well as in-depth characterization of the linkage network. Fragments resulted from enzymatic depolymerization were resolved by a porous graphitic carbon column followed by online tandem-MS for determining the modification site/residue. With high-resolution separation, two types of previously unknown structures were detected in the cross-linked fragments of 2-B-2 and 4-B-2. Based on the feature of resistance to NaBH4 reduction, these structures contain a GlcNAc residue modified at OH1. This special sugar unit likely derived from reducing end of the native polysaccharide could be a signature to discriminate subtle batch to batch variations.
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| 18. |
- Zhang, Tianji, et al.
(författare)
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Oligosaccharides mapping of nitrous acid degraded heparin through UHPLC-HILIC/WAX-MS
- 2020
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- Building blocks characterization is a significant approach for understanding the molecular structure of heparin and its derivatives. Nitrous acid (HONO) depolymerization of heparin generates oligosaccharides that maintain the epimerization conformation on C5 of the uronic acids, reflecting the authentic structure of the parental chain. HONO treatment at pH 1.5 selectively cleaves the bond between N-sulfated glucosamine and hexuronic acid, resulting mainly disaccharides, as well as tetra-, tri-, and mono-saccharides. The tetrasaccharides are derived from the structure of N-acetylated domains while tri-, and mono-saccharides are derived from the reducing or the non-reducing end of the heparin chain. The resulted oligosaccharides were separated and analyzed using a UHPLC-HILIC/WAX-MS method. We succeeded in the identification of 19 tetrasaccharides, 19 trisaccharides and 4 monosaccharides species, majority of which is structurally characterized. By comparing the theoretical possibilities and actual occurrence of the well-characterized tetrasaccharides, we demonstrated that the biosynthesis of heparin is a systematic process.
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| 19. |
- Zhao, Siran, et al.
(författare)
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Overview of the current procedures in synthesis of heparin saccharides
- 2024
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 339
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Tidskriftsartikel (refereegranskat)abstract
- Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 -> 4 glycosidic bonds, is the most widely used anticoagulant. To subvert the dependence on animal sourced heparin, alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar to natural heparin, or structurally defined oligosaccharides, are becoming hot subjects. Although the success by chemical synthesis of the pentasaccharide, fondaparinux, encourages to proceed through a chemical approach generating homogenous product, synthesizing larger oligos is still cumbersome and beyond reach so far. Alternatively, the chemoenzymatic pathway exhibited exquisite stereoselectivity of glycosylation and regioselectivity of modification, with the advantage to skip the tedious protection steps unavoidable in chemical synthesis. However, to a scale of drug production needed today is still not in sight. In comparison, a procedure of de novo biosynthesis in an organism could be an ultimate goal. The main purpose of this review is to summarize the current available/developing strategies and techniques, which is expected to provide a comprehensive picture for production of heparin saccharides to replenish or eventually to replace the animal derived products. In chemical and chemoenzymatic approaches, the methodologies are discussed according to the synthesis procedures: building block preparation, chain elongation, and backbone modification.
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| 20. |
- Cheng, Jie, et al.
(författare)
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Guanidimidazole-quanternized and cross-linked alkaline polymer electrolyte membrane for fuel cell application
- 2016
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Ingår i: Journal of Membrane Science. - : Elsevier BV. - 0376-7388 .- 1873-3123. ; 501, s. 100-108
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Tidskriftsartikel (refereegranskat)abstract
- A modified imidazole, namely guanidimidazole (GIm) was designed and synthesized as a novel quaternizing- and cross-linking agent for alkaline polymer electrolyte membrane fabrication. The resulting membrane was more alkali tolerant and swelling resistant than that quaternized purely by 1-methylimidazole owing to the enhanced resonance and cross-linking ability of GIm, the former confirmed by a LUMO (lowest unoccupied molecular orbital) energy calculation. The membrane also showed good ionic conductivity, mechanical strength and thermal stability. A H2/O2 fuel cell using the synthesized membrane showed a peak power density of 39 mW cm−2 at 50 °C. This work preliminarily demonstrates the beneficial effect of imidazole modification by both experimental and computational investigation; it provides a new cation design strategy that may potentially achieve simultaneous improvement of alkali-stability and swelling resistance of alkaline electrolyte membranes.
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| 21. |
- Franic, Iva, et al.
(författare)
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Climate, host and geography shape insect and fungal communities of trees
- 2023
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance indicating that human-mediated transport may serve as a pathway of the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.
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| 22. |
- Franic, Iva, et al.
(författare)
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Worldwide diversity of endophytic fungi and insects associated with dormant tree twigs
- 2022
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- International trade in plants and climate change are two of the main factors causing damaging tree pests (i.e. fungi and insects) to spread into new areas. To mitigate these risks, a large-scale assessment of tree-associated fungi and insects is needed. We present records of endophytic fungi and insects in twigs of 17 angiosperm and gymnosperm genera, from 51 locations in 32 countries worldwide. Endophytic fungi were characterized by high-throughput sequencing of 352 samples from 145 tree species in 28 countries. Insects were reared from 227 samples of 109 tree species in 18 countries and sorted into taxonomic orders and feeding guilds. Herbivorous insects were grouped into morphospecies and were identified using molecular and morphological approaches. This dataset reveals the diversity of tree-associated taxa, as it contains 12,721 fungal Amplicon Sequence Variants and 208 herbivorous insect morphospecies, sampled across broad geographic and climatic gradients and for many tree species. This dataset will facilitate applied and fundamental studies on the distribution of fungal endophytes and insects in trees.
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| 23. |
- Nie, Shisong, et al.
(författare)
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High Conductivity, Semiconducting, and Metallic PEDOT:PSS Electrode for All-Plastic Solar Cells
- 2023
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 28:6
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Tidskriftsartikel (refereegranskat)abstract
- Plastic electrodes are desirable for the rapid development of flexible organic electronics. In this article, a plastic electrode has been prepared by employing traditional conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) and plastic substrate polyethersulfone (PES). The completed electrode (Denote as HC-PEDOT:PSS) treated by 80% concentrated sulfuric acid (H2SO4) possesses a high electrical conductivity of over 2673 S/cm and a high transmittance of over 90% at 550 nm. The high conductivity is attributed to the regular arrangement of PEDOT molecules, which has been proved by the X-ray diffraction characterization. Temperature-dependent conductivity measurement reveals that the HC-PEDOT:PSS possesses both semiconducting and metallic properties. The binding force and effects between the PEDOT and PEI are investigated in detail. All plastic solar cells with a classical device structure of PES/HC-PEDOT:PSS/PEI/P3HT:ICBA/EG-PEDOT:PSS show a PCE of 4.05%. The ITO-free device with a structure of Glass/HC-PEDOT:PSS/Al4083/PM6:Y6/PDINO/Ag delivers an open-circuit voltage (V-OC) of 0.81 V, short-circuit current (J(SC) ) of 23.5 mA/cm(2), fill factor (FF) of 0.67 and a moderate power conversion efficiency (PCE) of 12.8%. The above results demonstrate the HC-PEDOT:PSS electrode is a promising candidate for all-plastic solar cells and ITO-free organic solar cells.
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| 24. |
- Pantoom, Supansa, et al.
(författare)
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RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein
- 2021
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Ingår i: Autophagy. - : Taylor & Francis. - 1554-8627 .- 1554-8635. ; 17:9, s. 2290-2304
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Tidskriftsartikel (refereegranskat)abstract
- Autophagosome formation is a fundamental process in macroautophagy/autophagy, a conserved self-eating mechanism in all eukaryotes, which requires the conjugating ATG (autophagy related) protein complex, ATG12-ATG5-ATG16L1 and lipidated MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). How the ATG12-ATG5-ATG16L1 complex is recruited to membranes is not fully understood. Here, we demonstrated that RAB33B plays a key role in recruiting the ATG16L1 complex to phagophores during starvation-induced autophagy. Crystal structures of RAB33B bound to the coiled-coil domain (CCD) of ATG16L1 revealed the recognition mechanism between RAB33B and ATG16L1. ATG16L1 is a novel RAB-binding protein (RBP) that can induce RAB proteins to adopt active conformation without nucleotide exchange. RAB33B and ATG16L1 mutually determined the localization of each other on phagophores. RAB33B-ATG16L1 interaction was required for LC3 lipidation and autophagosome formation. Upon starvation, a fraction of RAB33B translocated from the Golgi to phagophores and recruited the ATG16L1 complex. In this work, we reported a new mechanism for the recruitment of the ATG12-ATG5-ATG16L1 complex to phagophores by RAB33B, which is required for autophagosome formation.
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| 25. |
- Qu, Yanhua, 1974-, et al.
(författare)
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Ground tit genome reveals avian adaptation to living at high altitudes in the Tibetan plateau.
- 2013
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2071-
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Tidskriftsartikel (refereegranskat)abstract
- The ground tit (Parus humilis) is endemic to the Tibetan plateau. It is a member of family Paridae but it was long thought to be related to the ground jays because of their morphological similarities. Here we present the ground tit's genome and re-sequence two tits and one ground jay, to clarify this controversially taxonomic status and uncover its genetic adaptations to the Tibetan plateau. Our results show that ground tit groups with two tits and it diverges from them between 7.7 and 9.9 Mya. Compared with other avian genomes, ground tit shows expansion in genes linked to energy metabolism and contractions in genes involved in immune and olfactory perception. We also found positively selected and rapidly evolving genes in hypoxia response and skeletal development. These results indicated that ground tit evolves basic strategies and 'tit-to-jay' change for coping with the life in an extreme environment.
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| 26. |
- Zhang, Shunming, et al.
(författare)
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Adherence to a healthy lifestyle including sleep and sedentary behaviors and risk of metabolic dysfunction-associated steatotic liver disease in Chinese adults
- 2024
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Ingår i: Preventive Medicine. - 0091-7435. ; 184
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. Methods: This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. Results: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0–2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5–7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. Conclusion: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.
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| 27. |
- Zhang, Shunming, et al.
(författare)
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Dairy intake and risk of type 2 diabetes : results of a large prospective cohort
- 2023
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Ingår i: Food & Function. - 2042-6496. ; 14:21, s. 9695-9706
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Previous studies of primarily Western populations have consistently documented a lower risk of type 2 diabetes (T2D) among people with a higher yogurt intake, but an inconsistent association with milk intake. However, little is known about the association between dairy intake and risk of T2D among Chinese adults who consume considerably less dairy (mainly milk and yogurt) compared with Western populations. The aim is to investigate the associations of dairy intake with the risk of incident T2D in the general adult population in China. Methods: This cohort study consisted of 22 843 participants without prevalent cardiovascular disease, cancer, or diabetes at the baseline. Dietary data were collected using a validated food frequency questionnaire at the baseline (2013-2018); dairy intake was categorized into tertiles after zero consumers were taken as the reference. Incident T2D was ascertained by medical examinations and self-report of physician-diagnosed diabetes during follow-up visits. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In total, 735 incident T2D cases were recorded over a median follow-up of 4.0 years. Relative to zero consumers, the HRs (95% CIs) for incident T2D among participants in the highest tertiles were 0.70 (0.57, 0.87) for total dairy, 0.73 (0.60, 0.90) for milk, and 0.81 (0.66, 1.00) for yogurt. Such associations were slightly attenuated by additional adjustment for the body mass index. In addition, such inverse associations were robust in sensitivity analyses and consistent in most of the subgroups defined by baseline characteristics. Conclusion: Higher intakes of total dairy, milk, and yogurt were all associated with a lower risk of T2D among Chinese adults.
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| 28. |
- Zhang, Shunming, et al.
(författare)
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Inflammatory potential of diet and risk of nonalcoholic fatty liver disease : a prospective cohort study
- 2022
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 76:8, s. 1125-1132
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Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Diet is an important factor that can exacerbate or ameliorate chronic inflammation, which has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, no prospective study has yet investigated the relation between the inflammatory potential of diet and NAFLD. The aim of this study was to investigate the association between the inflammatory potential of the diet and the risk of NAFLD. Subject/methods: The study included 12,877 participants aged over 18 years (mean [standard deviation]: 39.4 [11.5] years). Dietary intake was assessed at baseline through food frequency questionnaires. Using white blood cell count as the inflammatory marker, we newly created a dietary inflammatory potential score by reduced rank regression and stepwise linear regression. NAFLD was identified by abdominal ultrasound during yearly health checkups. Cox proportional hazards regression models were used to estimate the association between the dietary inflammatory potential score and the risk of NAFLD. Results: During a median follow-up period of 4.2 years, 2744 first incident cases of NAFLD occurred. After adjustment for potential confounders, the multivariable hazards ratios (95% confidence intervals) for NAFLD across increasing quartiles of the dietary inflammatory potential score were 1.00 (reference), 1.01 (0.90, 1.13), 1.15 (1.03, 1.29), and 1.26 (1.13, 1.41), with P for trend <0.0001. This positive association appeared greater in men than in women (P for interaction = 0.02). Conclusions: Our results indicate that a dietary pattern with high inflammatory potential is associated with a higher risk of NAFLD. Such findings provide the support that inflammation may be a potential mechanism linking diet to the risk of NAFLD.
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| 29. |
- Zhang, Shunming, et al.
(författare)
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Protein foods from animal sources and risk of nonalcoholic fatty liver disease in representative cohorts from North and South China
- 2023
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 293:3, s. 340-353
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging evidence suggests that animal protein foods may increase the risk of nonalcoholic fatty liver disease (NAFLD). We therefore examined the NAFLD risk reduction related to substituting plant protein foods for animal protein foods.METHODS: The cohort in North China included 14,541 participants from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) study, and the cohort in South China included 1297 participants from the Guangzhou Nutrition and Health Study (GNHS). Dietary intake was assessed using validated food frequency questionnaires. NAFLD was ascertained by abdominal ultrasound. The Cox model was used to fit the substitution analysis.RESULTS: In the TCLSIH cohort, when replacing one type of animal protein food (eggs, processed meat, unprocessed red meat, poultry, and fish) with an equivalent serving of plant protein foods (nuts, legumes, and whole grains), the replacement of animal protein foods with whole grains showed the strongest benefit; substituting one serving per day of whole grains for an equal amount of eggs (hazard ratio [HR] = 0.89; 95% confidence interval [CI]: 0.79, 1.00), processed meat (HR = 0.76; 95% CI: 0.64, 0.91), unprocessed red meat (HR = 0.90; 95% CI: 0.81, 1.00), poultry (HR = 0.81; 95% CI: 0.72, 0.92), or fish (HR = 0.87; 95% CI: 0.78, 0.97) was associated with a lower risk of NAFLD. In both the TCLSIH and GNHS cohorts, replacing poultry with fish, nuts, legumes, or whole grains was associated with a lower risk of NAFLD. When different numbers of protein foods were simultaneously replaced, the risk reduction of NAFLD was stronger.CONCLUSIONS: Our findings suggest that replacing animal protein foods with plant protein foods is related to a significant reduction in NAFLD risk.
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