| 1. |
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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 5. |
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| 6. |
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| 7. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 8. |
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| 11. |
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| 12. |
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| 13. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 18. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 19. |
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| 20. |
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| 21. |
- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 22. |
- Li, Junjie, et al.
(författare)
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A Novel Dry Selective Isotropic Atomic Layer Etching of SiGe for Manufacturing Vertical Nanowire Array with Diameter Less than 20 nm
- 2020
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Semiconductor nanowires have great application prospects in field effect transistors and sensors. In this study, the process and challenges of manufacturing vertical SiGe/Si nanowire array by using the conventional lithography and novel dry atomic layer etching technology. The final results demonstrate that vertical nanowires with a diameter less than 20 nm can be obtained. The diameter of nanowires is adjustable with an accuracy error less than 0.3 nm. This technology provides a new way for advanced 3D transistors and sensors.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Ai, Jin Wei, et al.
(författare)
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Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms : An Analysis of Seven Patients in China
- 2020
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3–16 days), 7 with anorexia (7–22 days), 6 with upper abdominal discomfort (1–7 days), and 4 with nausea (1–7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.
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| 27. |
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| 28. |
- Ding, Long Hua, et al.
(författare)
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Nanozymes regulated by nitrogen element: Mechanism, design, and application
- 2024
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Ingår i: Advanced Powder Materials. - 2772-834X. ; 3:4
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Forskningsöversikt (refereegranskat)abstract
- Nanozymes, a category of nanomaterials endowed with enzyme-mimicking capabilities, have exhibited considerable potential across diverse application domains. This comprehensive review delves into the intricacies of regulating nanozymes through N elements, elucidating the mechanisms governing N element control in the design and application of these nanomaterials. The initial sections introduce the foundational background and significance of nanozymes. Subsequent exploration delves into the detailed discussion of N element regulation mechanisms on nanozymes, encompassing N vacancies, N doping, N coordination, and nitride. These regulatory pathways play an instrumental role in fine-tuning the catalytic activity and specificity of nanozymes. The review further scrutinizes practical applications of N element regulation on nanozymes, spanning sensing detection, infection therapy, tumor therapy, and pollutant degradation. In conclusion, it succinctly summarizes the current research findings and proposes future directions for development. This thorough investigation into the regulation of nanozymes by N elements anticipates precise control over their performance, thereby advancing the extensive utilization of nanozymes in the realms of biomedical and environmental applications.
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| 29. |
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| 30. |
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| 31. |
- Fa, Wenxin, et al.
(författare)
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Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants : A Population-Based Cohort Study
- 2023
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationships of neutrophils and cytokines with cognitive dysfunction are poorly defined. We aimed to investigate the association of peripheral blood absolute neutrophil count (ANC) with cognitive function in older adults and to further explore the mediating role of serum cytokines in this association.Methods: This population-based cohort study included 1 666 dementia-free participants (age ≥60 years) derived from baseline examinations (March–September 2018) of the Multimodal Intervention to Delay Dementia and Disability in Rural China (MIND-China); of these, 1 087 participants completed follow-up examinations in October–December 2019. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, and executive function at the baseline and follow-up examinations. We used Mindray BC-6800 automated hematology analyzer to measure ANC and Meso Scale Discovery to measure serum interleukin-6 (IL-6) and eotaxin-3.Results: The linear regression analysis of cross-sectional data at baseline (n = 1 666) suggested that increased ANC was significantly associated with a lower episodic memory z score (β coefficient: −0.149, 95% CI: −0.274 to −0.023) and lower long-delayed free recall z score (−0.216, −0.361 to −0.070). Serum IL-6 and eotaxin-3 could mediate 16.16% to 20.21% and 7.55% to 9.35%, respectively, of these associations. The analysis of longitudinal data (n = 1 087) showed a J-shaped relationship of ANC with decline in episodic memory z score (p for nonlinear = .049), and a U-shaped relationship between ANC and decline in long-delayed free recall z score (p for nonlinear = .043).Conclusions: Increased neutrophils are associated with poor cognitive performance and accelerated decline in episodic memory, and the cross-sectional association is partly mediated by serum cytokines.
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| 32. |
- Fang, Evandro F., et al.
(författare)
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A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.
- 2020
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Ingår i: Ageing Research Reviews. - : Elsevier BV. - 1568-1637. ; 64
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Tidskriftsartikel (refereegranskat)abstract
- One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the ‘one child policy’ and the ‘empty-nest elderly’ phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of ‘exercising more, eating less’, while other anti-ageing molecules from molecular gerontologists could help to improve ‘healthspan’ in the elderly. Machine learning, ‘Big Data’, and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).
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| 33. |
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| 34. |
- Kinyoki, DK, et al.
(författare)
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Mapping child growth failure across low- and middle-income countries
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 577:7789, s. 231-
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Tidskriftsartikel (refereegranskat)abstract
- Childhood malnutrition is associated with high morbidity and mortality globally1. Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood2. Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0–59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards3–5. The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization’s median growth reference standards for a healthy population6. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for example, states or provinces)7; the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes8. Building from our previous work mapping CGF in Africa9, here we provide the first, to our knowledge, mapped high-spatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99% of affected children live1, aggregated to policy-relevant first and second (for example, districts or counties) administrative-level units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications.
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| 35. |
- Li, Jingjing, et al.
(författare)
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Photothermal Aerogel Beads Based on Polysaccharides: Controlled Fabrication and Hybrid Applications in Solar-Powered Interfacial Evaporation, Water Remediation, and Soil Enrichment
- 2022
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Ingår i: ACS Applied Materials & Interfaces. - : American Chemical Society (ACS). - 1944-8252 .- 1944-8244. ; 14:44, s. 50266-50279
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Tidskriftsartikel (refereegranskat)abstract
- Solar-powered interfacial evaporation has emerged as an innovative and sustainable technology for clean water production. However, the rapid, mass and shape-controlled fabrication of three-dimensional (3D) steam generators (SGs) for versatile hybrid applications remains challenging. Herein, composite aerogel beads with self-contained properties (i.e., hydrophilic, porous, photothermal, and durable) are developed and demonstrated for threefold hybrid applications including efficient solar-powered interfacial evaporation, water remediation, and controlled soil enrichment. The rational incorporation of selected polysaccharides enables us to fabricate bead-like aerogels with rapid gelation, continuous processing, and enhanced ion adsorption. The composite beads can attain a high water evaporation rate of 1.62 kg m-2 h-1 under 1 sun. Meanwhile, high phosphate adsorption capacity of over 120 mg g-1 is achieved in broad pH (2.5-12.4) and concentration (200-1000 mg L-1) ranges of phosphate solutions. Gratifyingly, we demonstrate the first example of recycling biomaterials from interfacial SGs for controlled nutrient release, soil enrichment, and sustainable agriculture. The phosphate-saturated beads can be gradually broken down in the soil. Macronutrients (N, P, and K) can be slowly released in 50 days, sustaining the plant germination and growth in a whole growth stage. This work shines light on the mass and controlled fabrication of aerogel beads based on double-network biopolymers, not merely scaling up solar-powered interfacial evaporation but also considering water remediation, waste material disposal, and value-added conversion.
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| 36. |
- Liang, Xiaoyan, et al.
(författare)
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Association and interaction of TOMM40 and PVRL2 with plasma amyloid-β and Alzheimer's disease among Chinese older adults : a population-based study
- 2022
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 113, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies have identified Alzheimer's disease (AD)-associated SNPs in TOMM40 and PVRL2 genes, but the underlying mechanisms remain unknown. We examined their associations and interactions with AD risk and plasma biomarkers among Chinese older adults. This population-based study included 4876 participants. TOMM40(rs2075650) and PVRL2(rs6859) polymorphisms were detected using multiple-polymerase chain reaction amplification. Plasma Aβ40, Aβ42, and t-tau concentrations were measured using SIMOA in a subsample (n = 1257). AD was diagnosed following the international criteria. Data were analyzed using multiple logistic and general linear models. AD was diagnosed in 182 participants. The multiadjusted odds ratio of AD was 6.24 (95% CI 1.73–22.48) for TOMM40GG, 1.47 (0.89–2.42) for PVRL2AA, and 12.87 (3.97–41.73) for having both risk alleles (Pinteraction = 0.0003). Among APOEε3/ε3 carriers, the multiadjusted odds ratio of AD associated with TOMM40AG was 2.90(1.15–7.31). In biomarker subsample, TOMM40GG was significantly associated with lower plasma Aβ42 and the Aβ42-to-Aβ40 ratio (p < 0.05). TOMM40 genotype is differentially associated with AD risk depending on APOE genotype. TOMM40 and PVRL2 genes could interact to substantially increase AD risk, possibly through influencing Aβ metabolism.
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| 37. |
- Liang, Xiaoyan, et al.
(författare)
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Exosomal miR-532-5p induced by long-term exercise rescues blood–brain barrier function in 5XFAD mice via downregulation of EPHA4
- 2023
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of the blood–brain barrier, which develops early in Alzheimer's disease (AD), contributes to cognitive impairment. Exercise not only reduces the risk factors for AD but also confers direct protection against cognitive decline. However, the exact molecular mechanisms remain elusive, particularly whether exercise can liberate the function of the blood–brain barrier. Here, we demonstrate that long-term exercise promotes the clearance of brain amyloid-β by improving the function of the blood–brain barrier in 5XFAD mice. Significantly, treating primary brain pericytes or endothelial cells with exosomes isolated from the brain of exercised 5XFAD mice improves cell proliferation and upregulates PDGFRβ, ZO-1, and claudin-5. Moreover, exosomes isolated from exercised mice exhibit significant changes in miR-532-5p. Administration or transfection of miR-532-5p to sedentary mice or primary brain pericytes and endothelial cells reproduces the improvement of blood–brain barrier function. Exosomal miR-532-5p targets EPHA4, and accordingly, expression of EphA4 is decreased in exercised mice and miR-532-5p overexpressed mice. A specific siRNA targeting EPHA4 recapitulates the effects on blood–brain barrier-associated cells observed in exercised 5XFAD mice. Overall, our findings suggest that exosomes released by the brain contain a specific miRNA that is altered by exercise and has an impact on blood–brain barrier function in AD.
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| 38. |
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| 39. |
- Mao, Ming, et al.
(författare)
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Resting heart rate, cognitive function, and inflammation in older adults : a population-based study
- 2023
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Ingår i: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 35, s. 2821-2829
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Tidskriftsartikel (refereegranskat)abstract
- Background Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood.Methods This population-based cross-sectional study included 4510 dementia-free participants (age >= 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models.Results People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR >= 80 bpm (vs. 60-69 bpm) was significantly associated with the multivariable-adjusted beta coefficients of - 0.58 [95% confidence interval (CI), - 1.00, - 0.16] for MMSE score and - 0.08 (- 0.15, - 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (beta coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-alpha (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16).Conclusions There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.
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| 40. |
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| 41. |
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| 42. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 46. |
- Qu, Chang, et al.
(författare)
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Functional significance of asymmetrical retention of parental alleles in a hybrid pine species complex
- 2024
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Ingår i: Journal of Systematics and Evolution. - : John Wiley & Sons. - 1674-4918 .- 1759-6831. ; 62:1, s. 135-148
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid genomes usually harbor asymmetrical parental contributions. However, it is challenging to infer the functional significance of asymmetrical retention of parental alleles in hybrid populations of conifer trees. Here we investigated the diversity in the glutathione S-transferase (GST) gene family in a hybrid pine Pinus densata and its parents (Pinus tabuliformis and Pinus yunnanensis). Plant GSTs play major roles in protecting plants against biotic and abiotic stresses. In this study, 19 orthologous groups of GST genes were identified and cloned from these three species. We examined their expression in different tissues, and then purified the corresponding proteins to characterize their enzymatic activities and specificities toward different substrates. We found that among the 19 GST orthologous groups, divergence in gene expression and in enzymatic activities toward different substrates was prevalent. P. densata preferentially retained P. yunnanensis-like GSTs for 17 out of the 19 gene loci. We determined the first GST crystal structure from conifer species at a resolution of 2.19 Å. Based on this structure, we performed site-directed mutagenesis to replace amino acid residuals in different wild-types of GSTs to understand their functional impacts. Reciprocal replacement of amino acid residuals in native GSTs of P. densata and P. tabuliformis demonstrated significant changes in enzyme functions and identified key sites controlling GSTs activities. This study illustrates an approach to evaluating the functional significance of sequence variations in conifer genomes. Our study also sheds light on plausible mechanisms for controlling the selective retention of parental alleles in the P. densata genome.
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- Ren, Yifei, et al.
(författare)
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Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults : A population-based study
- 2024
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Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1550-1561
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults.METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models.RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05).DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults.
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| 49. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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