| 31. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 32. |
- Wang, Si-Yu, et al.
(författare)
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Kaempferia galanga L. : Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses
- 2021
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12
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Forskningsöversikt (refereegranskat)abstract
- K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.
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| 33. |
- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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| 34. |
- Xu, Chao-Qun, et al.
(författare)
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Genome sequence of Malania oleifera, a tree with great value for nervonic acid production
- 2019
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Malania oleifera, a member of the Olacaceae family, is an IUCN red listed tree, endemic and restricted to the Karst region of southwest China. This tree's seed is valued for its high content of precious fatty acids (especially nervonic acid). However, studies on its genetic makeup and fatty acid biogenesis are severely hampered by a lack of molecular and genetic tools. Findings We generated 51 Gb and 135Gb of raw DNA sequences, using Pacific Biosciences (PacBio) single-molecule real-time and 10x Genomics sequencing, respectively. A final genome assembly, with a scaffold N50 size of 4.65 Mb and a total length of 1.51Gb, was obtained by primary assembly based on PacBio long reads plus scaffolding with 10x Genomics reads. Identified repeats constituted approximate to 82% of the genome, and 24,064 protein-coding genes were predicted with high support. The genome has low heterozygosity and shows no evidence for recent whole genome duplication. Metabolic pathway genes relating to the accumulation of long-chain fatty acid were identified and studied in detail. Conclusions Here, we provide the first genome assembly and gene annotation for M. oleifera. The availability of these resources will be of great importance for conservation biology and for the functional genomics of nervonic acid biosynthesis.
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| 35. |
- Xu, Guangwei, et al.
(författare)
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Synthesis, properties, and top-gated metal-oxide-semiconductor field-effect transistors of p-type GaSb nanowires
- 2013
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 3:43, s. 19834-19839
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Tidskriftsartikel (refereegranskat)abstract
- High-quality GaSb nanowires (NWs) have been synthesized via chemical vapor deposition. The as-synthesized NWs have a zinc-blende structure with growth direction along a < 011 > direction. Raman spectrum of the GaSb NWs consists of two peaks, corresponding to the LO and TO phonon modes, respectively. The temperature dependence of the photoluminescence spectra shows a blue-shift as the temperature decreases from 300 to 13 K. The electrical properties of the GaSb NWs are investigated over a wide range of temperatures from 25 mK to 291 K. The results show that the GaSb NWs exhibit excellent p-type transistor performance at low temperatures (<40 K). The room-temperature hole density and mobility were found to be similar to 2.2 x 10(18) cm(-3) and similar to 14.2 cm(2) V-1 s(-1), respectively. The Schottky contact characteristics were observed and the barrier height was found to be similar to 14 meV. Our results show that the GaSb NWs could be used as building blocks for emerging p-type nanoelectronic devices in extremely low temperature environments.
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| 36. |
- Xu, Hui, et al.
(författare)
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Association of Lifespan Cognitive Reserve Indicator With Dementia Risk in the Presence of Brain Pathologies
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:10, s. 1184-1191
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Tidskriftsartikel (refereegranskat)abstract
- Importance Evidence on the association of lifespan cognitive reserve (CR) with dementia is limited, and the strength of this association in the presence of brain pathologies is unknown.Objective To examine the association of lifespan CR with dementia risk, taking brain pathologies into account.Design, setting, and participants This study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years). After excluding 420 individuals who had prevalent dementia, missing data on CR, or dropped out, 1602 dementia-free adults were identified at baseline and evaluated to detect incident dementia. During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018.Exposures Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest).Main outcomes and measures Dementia was diagnosed following international criteria. Neuropathologic evaluations for Alzheimer disease and other brain pathologies were performed in autopsied participants. The association of lifespan CR with dementia or brain pathologies was estimated using Cox regression models or logistic regression.Results Of the 1602 included participants, 1216 (75.9%) were women, and the mean (SD) age was 79.6 (7.5) years. During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer disease-related dementia (22.3%). The multiadjusted hazards ratios (HRs) of dementia were 0.77 (95% CI, 0.59-0.99) for participants in the middle CR score tertile and 0.61 (95% CI, 0.47-0.81) for those in the highest CR score tertile compared with those in the lowest CR score tertile. In autopsied participants, CR was not associated with most brain pathologies, and the association of CR with dementia remained significant after additional adjustment for brain pathologies (HR, 0.60; 95% CI, 0.42-0.86). The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37-0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18-0.62).Conclusions and relevance High lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.
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| 37. |
- Xu, Hui, et al.
(författare)
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Association of lifespan cognitive reserve indicator with the risk of mild cognitive impairment and its progression to dementia
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:6, s. 873-882
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The association of lifespan cognitive reserve (CR) with mild cognitive impairment (MCI) remains controversial. We aimed to examine the association of lifespan CR indicator with the risk of MCI and its progression to dementia, taking brain pathologies into account.Methods: In a community-based cohort study (mean age, 79 years) with annual followup (median, 5.16 years; maximum, 20 years), a cognitively intact group (n = 1182) and an MCI group (n = 420) were identified at baseline. During the follow-up, 611 participants died and underwent autopsies. CR indicator encompassing education, early life to late-life cognitive and social activities were obtained and tertiled.Results: The multi-adjusted hazard ratio (HR) of MCI was 0.72 (95% confidence interval [CI] 0.58 to 0.90) in the cognitively intact group, and the HR of dementia was 0.66 (95% CI 0.45 to 0.97) in the MCI group for participants with the highest CR indicator (reference: the lowest CR indicator). Among MCI participants with brain pathologies, dementia incidence was about 50% lower in people with the highest CR indicator than the lowest CR indicator.Discussion: High lifespan CR indicator reduces risk of MCI, and delays its progression to dementia.
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| 38. |
- Xu, Hui, et al.
(författare)
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Impact of Pore Structure on Two-Electron Oxygen Reduction Reaction in Nitrogen-Doped Carbon Materials : Rotating Ring-Disk Electrode vs. Flow Cell
- 2022
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Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- The impact of pore structure on the two-electron oxygen reduction reaction (ORR) in nitrogen-doped carbon materials is currently under debate, and previous studies are mainly limited to the rotating ring-disk electrode (RRDE) rather than the practical flow cell (FC) system. In this study, assisted by a group of reliable pore models, the impact of two pore structure parameters, that is, Brunauer–Emmett–Teller surface area (SBET) and micropore surface fraction (fmicro), on ORR activity and selectivity are investigated in both RRDE and FC. The ORR mass activity correlates positively to the SBET in the RRDE and FC because a higher SBET can host more active sites. The H2O2 selectivity is independent of fmicro in the RRDE but correlates negatively to fmicro in the FC. The inconsistency results from different states of the electrode in the RRDE and the FC. These insights will guide the design of carbon materials for H2O2 synthesis.
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| 39. |
- Xu, Hui, et al.
(författare)
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Osteoporosis and Osteopenia Among Patients With Type 2 Diabetes Aged >= 50 : Role of Sex and Clinical Characteristics
- 2020
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Ingår i: Journal of clinical densitometry. - : Elsevier BV. - 1094-6950 .- 1559-0747. ; 23:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Introduction/Background: Although some studies have explored the association of adiposity and life habits (such as smoking) with osteoporosis and osteopenia among type 2 diabetes mellitus (T2DM) patients, the association between diabetic clinical characteristics (especially hypoglycemic drug use) and osteoporosis/ osteopenia remains unclear. This study aimed to investigate the relationship of clinical characteristics with osteoporosis and osteopenia among T2DM patients by sex. Methods: A total of 1222 T2DM patients aged >= 50 were included in the present study. Information on demographic, anthropometric and clinical characteristics was collected from medical records. Bone mineral density was assessed by dual-energy X-ray absorptiometry densitometer. Multiple adjusted logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of osteoporosis and osteopenia related to clinical characteristics. Results: Of all participants, the prevalence of osteoporosis and osteopenia was 9.2% and 41.3%, respectively, and they were higher in females (14.7% and 48.5%) than in males (2.8% and 33%). After adjustment for potential confounders, the results showed that overweight (OR = 0.59; 95 % CI, 0.42-0.81) and obesity (OR = 0.35; 95% CI, 0.24-0.50) were related to decreased odds of osteoporosis and osteopenia in both male and female T2DM patients, poor glycemic control (OR = 1.63; 95% CI, 1.08-2.47) was associated with increased odds of osteoporosis and osteopenia in males, and metformin treatment (OR = 0.65; 95% CI, 0.43-0.99) was associated with decreased odds of osteoporosis and osteopenia in females. Conclusions: Better glycemic management and rational choice of antidiabetic medication might be promising to prevent osteoporosis in T2DM patients. Further longitudinal studies are warranted to explore the association between antidiabetic treatment and osteoporosis.
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| 40. |
- Xu, Hong-Tao, et al.
(författare)
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Effects of fucosylated milk of goat and mouse on Helicobacter pylori binding to Lewis b antigen
- 2004
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Ingår i: World Journal of Gastroenterology. - Beijing : WJG Press. - 1007-9327 .- 2219-2840. ; 10:14, s. 2063-2066
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Tidskriftsartikel (refereegranskat)abstract
- Aim:To evaluate the effects of animal milk containing fucosylated antigens on Helicobacter pylori (H pylon) binding to Lewis b antigen. Methods:A mammary gland expression vector containing human α1-3/4-fucosyltransferase cDNA sequences was constructed. Transient expression of human(α1-3/4-fucosyltransferase cDNA in goat mammary cell and establishment of transgenic mice were performed. The adhesion inhibitory properties of milk samples were analyzed by using Hpylori. Results: Goat milk samples were found to inhibit bacterial binding to Lewis b antigen. The highest inhibition was observed 42 h after injection of the plasmid. The binding activity of Hpylori to Lewis b antigen reduced mostly, by 83%, however milk samples from transgenic mice did not inhibit Hpylori binding to Lewis b antigen. Conclusion: The use of “humanized“ animal milk produced by the transgenic introduction of fucosylated antigen can perhaps provide an alternative therapy and preventive measure for Hpylori infection.
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