| 1. |
- Wei, Yanfei, et al.
(författare)
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Stalled oligodendrocyte differentiation in IDH-mutant gliomas.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Roughly 50% of adult gliomas harbor isocitrate dehydrogenase (IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized.Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers.Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas.Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.
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| 2. |
- Fu, Li, et al.
(författare)
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Effects of long-term exposure to ambient fine particulate matter and its specific components on blood pressure and hypertension incidence
- 2024
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Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 184
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) and its specific components with hypertension and blood pressure is limited. Methods: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007–2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. Results: Each interquartile range (IQR = 16.80 μg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR μg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42−, NO3−, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. Conclusions: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.
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| 3. |
- Li, Suyang, et al.
(författare)
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Association between social capital and oral health among adults aged 50 years and over in China: a cross-sectional study
- 2022
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Ingår i: Bmc Oral Health. - : Springer Science and Business Media LLC. - 1472-6831. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Social capital has a potential effect in protecting oral health among population. However, no study has explored the association between social capital and oral health in the Chinese context. Due to the unique culture, political, social context in China, it is important to understand their association in the Chinese context. The study aims to investigate the association between cognitive and structural dimensions of social capital with edentulism among adults aged 50 years and over in China. Method The study used data from the WHO SAGE (Study on Global AGEing and Adult Health) wave 1 China component. Structural social capital was operationalized as social participation. Cognitive social capital was operationalized as perceived community trust and perceived community safety. Community-level social capital was measured by aggregating individual-level social capital into community level. Oral health was measured using a final marker of oral health status, self-reported edentulism. A 2-level multilevel logistic regression was used to evaluate the association between different dimensions of social capital and oral health. Results In total, 12,856 individuals were included in the study, the overall prevalence of edentulism was 9.1% (95% CI 8.3-10.0). Multilevel logistic analysis revealed that individual-level social capital and community-level social capital are independently associated with edentulism. Individuals with low structural social capital and living in areas with low structural social capital have, respectively, 1.54 (95% CI 1.18-2.01) and 2.14 (95% CI 1.47-3.12) times higher odds for edentulism, after adjustment for potential confounders (age, sex, marital status, residence locality, wealth, education level, chronic conditions) and a potential mediator(smoking). Conclusions Living in a community with lower structural social capital and individual with low structural social capital is associated with higher risk for edentulism among adults aged 50 years and over in China.
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| 4. |
- Li, X., et al.
(författare)
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The association of cooking fuels with cataract among adults aged 50 years and older in low- and middle-income countries: Results from the WHO Study on global AGEing and adult health (SAGE)
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 790
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Tidskriftsartikel (refereegranskat)abstract
- Reducing household air pollution and protecting eye health are essential to achieve the Sustainable Development Goals (SDGs). There is contradictory evidence about the association between cooking fuels and cataract among adults aged 50 years and older. WHO Study on global AGEing and adult health (SAGE) was conducted in six low- and middle-income countries (LMICs). We used propensity-score method (inverse probability of weighting) and logistic regression to examine the association between cooking fuels and self-reported cataract. Odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated. Overall, use of unclean fuels was associated with an adjusted OR of cataract of 1.42 (95%CIs, 1.29–1.56). In subgroup analysis, unclean cooking fuels increased 1.71 (95%CI, 1.46–2.01) and 1.53 (95%CI, 1.30–1.79) times the risk of cataract in India and China, respectively, whereas no association was found in other countries. In gender-stratified analyses, unclean fuel use was associated with a 1.27 (95%CI, 1.13–1.44) times risk for males and 1.67 (95%CI, 1.44–1.94) times risk for females. Higher cataract risk attributed to unclean fuels was observed among those aged over 60 (1.45; 95%CI, 1.28–1.64) than people aged under 60 (1.39; 95%CI, 1.20–1.62). OR was higher in rural area (1.74; 95%CI, 1.51–2.00) than urban area (1.24; 95%CI, 1.09–1.41). Our results indicate that unclean fuels may be associated with self-reported cataract, but it varied among different LMICs. Higher risk was found in females, people older than 60 years old and those who live in rural areas. The result of this study provides useful information to support transition to clean household energy and eye health promotion in LMICs. Greater efforts should be taken to protect vulnerable populations. © 2021 Elsevier B.V.
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| 5. |
- Li, X., et al.
(författare)
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The effect of polluting cooking fuels on depression among older adults in six low- and middle-income countries
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 838
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about the association between polluting cooking fuel and depression among older adults living in low-and middle-income countries (LMICs).Objective: To evaluate the association between polluting cooking fuel and depression in older population of LMICs.Methods: We derived data from WHO Study on global AGEing and adult health (SAGE), which was conducted in six LMICs including China, India, Ghana, South Africa, Mexico and Russia. We applied logistic regression with the propensity score method to examine the relationship of polluting cooking fuel and depression among adults >= 50 years old.Results: Overall, the odds ratio (OR) of depression was 1.57 [95% confidence intervals (CIs), 1.26-1.93] for older adults relying on polluting cooking fuel in six LMICs. In India and China, polluting cooking fuel was associated with depression with ORs of 2.06 (95%CI, 1.44-2.94) and 1.59 (95%CI, 1.01-2.49), respectively. Positive OR of depression was identified for those polluting cooking fuel users aged over 65 years old (OR, 1.65; 95%CI,1.16-2.36) and those aged 50-65 (OR, 1.50; 95%CI,1.14-1.97). Polluting cooking fuel was associated with depression for females (OR, 1.80; 95%CI, 1.32-2.46), however we did not observe significant association for males. Positive effect of polluting cooking fuel was identified in both rural (OR, 1.72; 95%CI, 1.26-2.34) and urban areas (OR, 1.44; 95%CI, 1.07-1.95). For individuals relying on solid fuel, cooking in a room used for living/sleeping and using open stove/ fire was associated with depression with ORs of 1.30 (95%CI, 1.14-1.48) and 1.15 (95%CI, 1.01-1.31), respectively. However, no significant effect was identified for hood.Conclusion: Polluting cooking fuel was related to depressive symptoms among older adults in LMICs. In addition, cooking ventilation could be useful intervention to control health hazard of solid fuel.
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| 6. |
- Qi, Liang, et al.
(författare)
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Dehydrogenation of Propane and n-Butane Catalyzed by Isolated PtZn4 Sites Supported on Self-Pillared Zeolite Pentasil Nanosheets
- 2022
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 12:18, s. 11177-11189
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Tidskriftsartikel (refereegranskat)abstract
- Propene and 1,3-butadiene are important building-block chemicals that can be produced by dehydrogenation of propane and butane on Pt catalysts. A challenge is to develop highly active and selective catalysts that are resistant to deactivation by Pt sintering and coke formation. We have recently shown (Qi , J. Am. Chem. Soc. 2021, 143, 21364-21378) that these objectives can be met for propane dehydrogenation (PDH) using atomically dispersed Pt anchored to neighboring SiOZn-OH groups bonded to the framework of dealuminated zeolite BEA. In the present study, we demonstrate that significantly superior performance can be achieved using self-pillared pentasil (SPP) zeolite nanosheets as supports. Following catalyst reduction in H-2, atomic resolution, scanning transmission electron microscopy (STEM), and X-ray absorption spectroscopy (XAS) indicate that Pt is stabilized in structures well approximated as ( Si-O-Zn)(4-5)Pt. These species are highly active, selective, and stable for PDH to give propene and for n-butane dehydrogenation (BDH) to give 1,3-butadiene. No catalyst deactivation was observed after 12 days of time on stream, and the selectivity remained at nearly 100% for PDH conducted at 823 K and a weight hourly space velocity (WHSV) of 1350 h(-1). The apparent rate coefficient for PDH on this catalyst is significantly higher than that reported previously for Pt-containing catalysts. For BDH at 823 K and a WHSV of 3560 h(-1), the selectivity to butene isomers and 1,3-butadiene is 98.9%, and the selectivity to 1,3-butadiene is 45%. We propose that the high catalyst stability observed during PDH and BDH is a consequence of a large fraction of the Pt-containing centers being located on the external surface of the zeolite nanosheets, where nascent coke precursors can desorb before condensing to form coke.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- Shi, Yuanping, et al.
(författare)
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Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide‑induced acute inflammatory apoM‑/‑ mice
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:4, s. 3117-3126
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Tidskriftsartikel (refereegranskat)abstract
- apolipoproteinM(apoM)mayserveaprotectiverole inthedevelopmentofinflammation.Nuclearfactor‑κB(nF-κB) and its downstream factors (including a number of inflammatory cytokines and adhesion molecules) are essential for the regulation of inflammatory processes. In the present study, the importance of apoM in lipopolysaccharide (LPS)‑induced acute inflammation and its potential underlying mechanisms, were investigated using an apoM‑knockout mouse model. The levels of inducible nitric oxide synthase (iNOS), NF‑κB, interleukin (IL)‑1β, intercellular adhesion molecule 1 (ICAM‑1) and vascular cell adhesion protein 1 (VCAM‑1) were detected using reverse transcription‑quantitative PCR and western blotting. The serum levels of IL‑6 and IL‑10 were detected using Luminex technology. The results demonstrated that the protein levels of inoS, nF-κB, il-1β, ICAM‑1 and VCAM‑1 were significantly increased in apoM-/- mice compared with those in apoM+/+ mice. In addition, two‑way ANOVA revealed that the interaction between apoM and LPS had a statistically significant effect on a number of factors, including the mRNA expression levels of hepatic iNOS, NF‑κB, il-1β, icaM-1 and VCAM‑1. Notably, the effects of apoM and 10 mg/kg LPS on the levels of IL‑6 and IL‑10 were the opposite of those induced by 5 mg/kg LPS, which could be associated with the dual anti‑ and pro‑inflammatory effects of IL‑6 and IL‑10. Collectively, the results of the present study revealed that apoM is an important regulator of inflammatory cytokine and adhesion molecule production in LPS‑induced inflammation, which may consequently be associated with the severity of inflammation. These findings indicated that the anti‑inflammatory effects of apoM may partly result from the inhibition of the nF-κB pathway.
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| 10. |
- Traylor, Matthew, et al.
(författare)
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Genetic basis of lacunar stroke : a pooled analysis of individual patient data and genome-wide association studies
- 2021
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Ingår i: The Lancet Neurology. - 1474-4422. ; 20:5, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease. Methods: We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium. Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation. Findings: Our meta-analysis comprised studies from Europe, the USA, and Australia, including 7338 cases and 254 798 controls, of which 2987 cases (matched with 29 540 controls) were confirmed using MRI. Five loci (ICA1L-WDR12-CARF-NBEAL1, ULK4, SPI1-SLC39A13-PSMC3-RAPSN, ZCCHC14, ZBTB14-EPB41L3) were found to be associated with lacunar stroke in the European or transethnic meta-analyses. A further seven loci (SLC25A44-PMF1-BGLAP, LOX-ZNF474-LOC100505841, FOXF2-FOXQ1, VTA1-GPR126, SH3PXD2A, HTRA1-ARMS2, COL4A2) were found to be associated in the multi-trait analysis with cerebral white matter hyperintensities (n=42 310). Two of the identified loci contain genes (COL4A2 and HTRA1) that are involved in monogenic lacunar stroke. The TWAS identified associations between the expression of six genes (SCL25A44, ULK4, CARF, FAM117B, ICA1L, NBEAL1) and lacunar stroke. Pathway analyses implicated disruption of the extracellular matrix, phosphatidylinositol 5 phosphate binding, and roundabout binding (false discovery rate <0·05). Mendelian randomisation analyses identified positive associations of elevated blood pressure, history of smoking, and type 2 diabetes with lacunar stroke. Interpretation: Lacunar stroke has a substantial heritable component, with 12 loci now identified that could represent future treatment targets. These loci provide insights into lacunar stroke pathogenesis, highlighting disruption of the vascular extracellular matrix (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1), pericyte differentiation (FOXF2, GPR126), TGF-β signalling (HTRA1), and myelination (ULK4, GPR126) in disease risk. Funding: British Heart Foundation.
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