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Sökning: WFRF:(Xiao Jun)

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1.
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
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4.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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5.
  • Kristan, Matej, et al. (författare)
  • The Ninth Visual Object Tracking VOT2021 Challenge Results
  • 2021
  • Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
  • Konferensbidrag (refereegranskat)abstract
    • The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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6.
  • Zhang, Huai, et al. (författare)
  • A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
  • 2024
  • Ingår i: Hepatology international. - 1936-0541.
  • Tidskriftsartikel (refereegranskat)abstract
    • With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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7.
  • Jin, Ying-Hui, et al. (författare)
  • Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
  • 2020
  • Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
  • 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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8.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • 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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9.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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10.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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11.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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12.
  • Fang, Evandro F., et al. (författare)
  • 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
  • Ingår i: Ageing Research Reviews. - : Elsevier BV. - 1568-1637. ; 64
  • 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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13.
  • Kristanl, Matej, et al. (författare)
  • The Seventh Visual Object Tracking VOT2019 Challenge Results
  • 2019
  • Ingår i: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
  • Konferensbidrag (refereegranskat)abstract
    • The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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14.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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15.
  • Li, Lili, et al. (författare)
  • Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice
  • 2012
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 511:1, s. 4-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia. Without challenge, the heparanase overexpression did not significantly affect the mice in response to mechanical, cold and heat stimulation. Unilateral subcutaneous administration of carrageenan produced hypersensitivity to mechanical and cold in both wildtype and the heparanase overexpression (Hpa-tg) mice 24h after treatment. In comparison to wildtype animals, the Hpa-tg mice showed significantly reduced mechanical and cold hypersensitivity. This may, at least partially, due to the reduced mast cell infiltration at the site of inflammation in Hpa-tg mice. These data support a role for heparanase that reduces localized inflammation and inflammatory hyperalgesia in mice.
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16.
  • Li, Youbing, et al. (författare)
  • Electrochemical Lithium Storage Performance of Molten Salt Derived V2SnC MAX Phase
  • 2021
  • Ingår i: Nano-Micro Letters. - : Springer. - 2311-6706 .- 2150-5551. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • MAX phases are gaining attention as precursors of two-dimensional MXenes that are intensively pursued in applications for electrochemical energy storage. Here, we report the preparation of V2SnC MAX phase by the molten salt method. V2SnC is investigated as a lithium storage anode, showing a high gravimetric capacity of 490 mAh g(-1) and volumetric capacity of 570 mAh cm(-3) as well as superior rate performance of 95 mAh g(-1) (110 mAh cm(-3)) at 50 C, surpassing the ever-reported performance of MAX phase anodes. Supported by operando X-ray diffraction and density functional theory, a charge storage mechanism with dual redox reaction is proposed with a Sn-Li (de)alloying reaction that occurs at the edge sites of V2SnC particles where Sn atoms are exposed to the electrolyte followed by a redox reaction that occurs at V2C layers with Li. This study offers promise of using MAX phases with M-site and A-site elements that are redox active as high-rate lithium storage materials.
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17.
  • Liu, Yong, et al. (författare)
  • Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
  • 2017
  • Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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18.
  • Luo, Yifei, et al. (författare)
  • Technology Roadmap for Flexible Sensors
  • 2023
  • Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
  • Forskningsöversikt (refereegranskat)abstract
    • Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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19.
  • Luo, Ziyu, et al. (författare)
  • An Efficient Deep-Subwavelength Second Harmonic Nanoantenna Based on Surface Plasmon-Coupled Dilute Nitride GaNP Nanowires
  • 2021
  • Ingår i: Nano Letters. - : AMER CHEMICAL SOC. - 1530-6984 .- 1530-6992. ; 21:8, s. 3426-3434
  • Tidskriftsartikel (refereegranskat)abstract
    • High-index semiconductor nanoantennae represent a powerful platform for nonlinear photon generation. Devices with reduced footprints are pivotal for higher integration capacity and energy efficiency in photonic integrated circuitry (PIC). Here, we report on a deep subwavelength nonlinear antenna based on dilute nitride GaNP nanowires (NWs), whose second harmonic generation (SHG) shows a 5-fold increase by incorporating similar to 0.45% of nitrogen (N), in comparison with GaP counterpart. Further integrating with a gold (Au) thin film-based hybrid cavity achieves a significantly boosted SHG output by a factor of similar to 380, with a nonlinear conversion efficiency up to 9.4 x 10(-6) W-1. In addition, high-density zinc blende (ZB) twin phases were found to tailor the nonlinear radiation profile via dipolar interference, resulting in a highly symmetric polarimetric pattern well-suited for coupling with polarization nano-optics. Our results manifest dilute nitride nanoantenna as promising building blocks for future chip-based nonlinear photonic technology.
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20.
  • Nie, Huizhen, et al. (författare)
  • The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
  • 2021
  • Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
  • Tidskriftsartikel (refereegranskat)abstract
    • Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
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21.
  • Reitsma, Marissa B., et al. (författare)
  • Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015
  • 2017
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 389:10082, s. 1885-1906
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.
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22.
  • Wen, Wanqing, et al. (författare)
  • Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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23.
  • Yuan, Jin-Na, et al. (författare)
  • Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes
  • 2021
  • Ingår i: World Journal of Pediatrics. - : Zhejiang University Press. - 1708-8569 .- 1867-0687. ; 17:1, s. 99-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population. Methods Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes. Results Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged >= 11 years. Conclusions Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.
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24.
  • Zhang, Xiao-Dong, et al. (författare)
  • Establishment and assessments of a new model for the postoperative fatigue syndrome by major small intestinal resection in rats
  • 2011
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:11, s. 1302-1309
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Postoperative fatigue syndrome (POFS) is a general and main complication after surgery. However, there is no stable and standardized animal model for POFS. The aim of the present study was to establish a rodent model of POFS by small intestinal resection, with POFS evaluated by acknowledged physical and behavioral methods. Material and Methods. Forty-two Sprague-Dawley rats were randomly divided into four groups according to the length of a "middle" small intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70% groups, with corresponding lengths of small intestinal resections. Following surgery, the general state of health was evaluated. Tail suspension test, open field test and Morris water maze test were used to evaluate the degree of POFS. Serum albumin, transferrin, prealbumin and fibronectin were measured to assess the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Results. As compared with the other three groups, the 70% small intestinal resection group showed the worst general state of health, decreased strength of the tail suspension test and decreased score of Morris water maze test (p < 0.05) after operation. All rats in whom the small intestinal resection was done demonstrated a certain degree of malnutrition and behavior of depression, and the 70% resection group had the lowest levels of transferrin, prealbumin and fibronectin as compared with the other groups (p < 0.05), as well as decreased SOD and increased MDA in serum (p < 0.05). Conclusions. Resection of 70% of the small intestine resulted in typical characteristics of POFS. As this procedure is simple, stable and easily reproducible, it may serve as a model for research on POFS.
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25.
  • Zhong, Jun, et al. (författare)
  • A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
  • 2020
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 112:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
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26.
  • Zhou, Xiang-Yu, et al. (författare)
  • TRAF6 as the Key Adaptor of TLR4 Signaling Pathway Is Involved in Acute Pancreatitis
  • 2010
  • Ingår i: PANCREAS. - 0885-3177. ; 39:3, s. 359-366
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To study the potential role of tumor necrosis factor receptor-associated factor 6 (TRAF6) as the key adaptor of the toll-like receptor 4 (TLR4) signaling pathway in acute pancreatitis (AP) in mice. Methods: Acute pancreatitis was induced by 7 intraperitoneal injections of cerulein in TLR4-deficient (TLR4-Def) and TLR4 wild-type (TLR4-WT) mice. Inflammatory severity was scored and evaluated based on pathological study. TRAF6 expression was determined by reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry. Results: Acute pancreatitis was successfully induced in both mice strains, but the inflammatory progression was different. In TLR4-Def mice, pancreatic inflammation was blunt and mild first, then became increasingly intensive and peaked at the later stage, whereas in the TLR4-WT mice, the response was fast initiated and peaked at the early stage of AP, then alleviated gradually. TRAF6 expression in TLR4-Def mice was significantly higher than that in the TLR4-WT mice. Immunohistochemistry located TRAF6 expressed mainly in the pancreatic acinar cells. Conclusions: The TLR4-TRAF6 signaling pathway is critically involved in AP. Other signaling pathways beyond TLR4 may participate in the pancreatic inflammatory process via TRAF6. As a convergence point of the TLR4-dependent and the TLR4-independent signaling pathways, TRAF6 plays an important role in AP.
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27.
  • An, Junghwa, et al. (författare)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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28.
  • Azhar, Salman, et al. (författare)
  • Novel ABCA1 peptide agonists with antidiabetic action
  • 2019
  • Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 480, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice. CS6253 increased insulin secretion both under basal conditions and in response to high glucose stimulation in pancreatic INS-1 β-cells rendered leptin receptor deficient with specific siRNA. Additional in vitro cell studies suggest that the CS6253 agonist attenuates hepatic gluconeogenesis and glucose transport. It also potentiates insulin-stimulated glucose uptake and utilization. These observed anti-diabetic actions suggest additional benefits of the CS6253 and T6991-2 ABCA1 peptide agonists for cardiovascular disease beyond their direct anti-atherosclerosis properties previously described.
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29.
  • Bi, Xiao Jun, et al. (författare)
  • Chapter 5 Dark Matter and New Physics Beyond the Standard Model with LHAASO
  • 2022
  • Ingår i: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 46:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to reveal the nature of dark matter, it is crucial to detect its non-gravitational interactions with the standard model particles. The traditional dark matter searches focused on the so-called weakly interacting massive particles. However, this paradigm is strongly constrained by the null results of current experiments with high precision. Therefore there is a renewed interest of searches for heavy dark matter particles above TeV scale. The Large High Altitude Air Shower Observatory (LHAASO) with large effective area and strong background rejection power is very suitable to investigate the gamma-ray signals induced by dark matter annihilation or decay above TeV scale. In this document, we review the theoretical motivations and background of heavy dark matter. We review the prospects of searching for the gamma-ray signals resulted from dark matter in the dwarf spheroidal satellites and Galactic halo for LHAASO, and present the projected sensitivities. We also review the prospects of searching for the axion-like particles, which are a kind of well motivated light pseudo-scalars, through the LHAASO measurement of the very high energy gamma-ray spectra of astrophysical sources.
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30.
  • Byun, Jinyoung, et al. (författare)
  • Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
  • 2022
  • Ingår i: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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31.
  • Bäckhed, Fredrik, 1973, et al. (författare)
  • Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
  • 2015
  • Ingår i: Cell Host & Microbe. - Cambridge : Elsevier BV. - 1931-3128 .- 1934-6069. ; 17:5, s. 690-703
  • Tidskriftsartikel (refereegranskat)abstract
    • The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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32.
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33.
  • Carlsson-Jonsson, Anna, et al. (författare)
  • N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats
  • 2014
  • Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 738, s. 319-325
  • Tidskriftsartikel (refereegranskat)abstract
    • Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the bioclistribution and stability of the peptides. Most of the examined compounds alleviated mechanical alloclynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by arty of the compounds tested. Most of the amino acids in the heptapepticle structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapepticle and its N-Lerminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
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34.
  • Chen, Jun, et al. (författare)
  • Identifying Genetic Signatures of Natural Selection Using Pooled Population Sequencing in Picea abies
  • 2016
  • Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 6:7, s. 1979-1989
  • Tidskriftsartikel (refereegranskat)abstract
    • The joint inference of selection and past demography remain a costly and demanding task. We used next generation sequencing of two pools of 48 Norway spruce mother trees, one corresponding to the Fennoscandian domain, and the other to the Alpine domain, to assess nucleotide polymorphism at 88 nuclear genes. These genes are candidate genes for phenological traits, and most belong to the photoperiod pathway. Estimates of population genetic summary statistics from the pooled data are similar to previous estimates, suggesting that pooled sequencing is reliable. The nonsynonymous SNPs tended to have both lower frequency differences and lower F-ST values between the two domains than silent ones. These results suggest the presence of purifying selection. The divergence between the two domains based on synonymous changes was around 5 million yr, a time similar to a recent phylogenetic estimate of 6 million yr, but much larger than earlier estimates based on isozymes. Two approaches, one of them novel and that considers both F-ST and difference in allele frequencies between the two domains, were used to identify SNPs potentially under diversifying selection. SNPs from around 20 genes were detected, including genes previously identified as main target for selection, such as PaPRR3 and PaGI.
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35.
  • Chen, Yi-Jing, et al. (författare)
  • Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting
  • 2023
  • Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773.
  • Tidskriftsartikel (refereegranskat)abstract
    • The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 mu A cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems. Three perylene diimide (PDI) polymers were designed and synthesized such that the molecular orientation of the PDI units was regulated to create and modulate their built-in electric fields. Due to the large dipole moment and interfacial electric field, oPDI enables an extraordinary photocurrent density of 115.1 mu A & sdot; cm-2, which is 11.5 and 26.8 times that of mPDI and pPDI, respectively.image
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36.
  • Chen, Zhiwen, et al. (författare)
  • Interface engineering of NiS@MoS2 core-shell microspheres as an efficient catalyst for hydrogen evolution reaction in both acidic and alkaline medium
  • 2021
  • Ingår i: Journal of Alloys and Compounds. - : ELSEVIER SCIENCE SA. - 0925-8388 .- 1873-4669. ; 853
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrochemical splitting of water is one of the most reliable and effective ways for the sustainable production of pure hydrogen on a large scale, while the core of this technology lies in the development of highly active non-noble-metal-based electrocatalysts to lower the large dynamic overpotentials of electrode materials. Here, an interface engineering strategy is demonstrated to construct an efficient and stable catalyst based on NiS@MoS2 core-shell hierarchical microspheres for the hydrogen evolution reactions (HER). The ultrathin MoS2 nanosheets in-situ grow on the surface of NiS hierarchical micro-sized spheres constructed by porous nanoplates, endowing the composites with rich interfaces, well-exposed electroactive edges, high structural porosity and fast transport channels. These advantages are favorable for the improvement of catalytic sites and the transport of catalysis-relevant species. More importantly, the intimate contact between MoS2 nanosheets and NiS nanoplates synergistically favors the chemical sorption of hydrogen intermediates, thereby reducing the reaction barrier and accelerating the HER catalytic process. As a result, the optimized NiS@MoS2 catalyst manifests impressive HER activity and durability, with a low overpotential of 208 mV in 0.5 M H2SO4 and 146 mV in 1.0 M KOH at 10 mA cm(-2), respectively. This work not only provides an effective way to construct core-shell hierarchical microspheres but also a multiscale strategy to regulate the electronic structure of heterostructured materials for energy-related applications. (C) 2020 Elsevier B.V. All rights reserved.
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37.
  • Cho, Yoon Shin, et al. (författare)
  • Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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38.
  • Ding, Jun-Li, et al. (författare)
  • Attenuation of Acute Pancreatitis by Peroxisome Proliferator-Activated Receptor-α in Rats: The Effect on Toll-Like Receptor Signaling Pathways
  • 2013
  • Ingår i: Pancreas. - : Lippincott, Williams and Wilkins. - 0885-3177 .- 1536-4828. ; 42:1, s. 114-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The peroxisome proliferator-activated receptor-α (PPAR-α) has attracted considerable attention for its anti-inflammatory properties; however, Toll-like receptor (TLR) pathways have an essential proinflammatory role in acute pancreatitis (AP). This study aimed to evaluate the attenuation of inflammation by PPAR-α and to investigate the interaction between PPAR-α and TLR pathways in AP.Methods: Acute pancreatitis was induced in rats by administration of cerulein. The PPAR-α agonist WY14643 and/or antagonist MK886 was administered. The severity of AP was determined by measuring serum amylase, lipase, Ca2+, pathological changes, myeloperoxidase activity, serum levels of interleukin (IL)-6, and intercellular adhesion molecule-1 (ICAM-1). The TLR2 and TLR4 messenger RNA (mRNA) and proteins were determined by real-time reverse transcriptase polymerase chain reaction and Western blotting, respectively. The mRNA expressions of target molecules of TLR pathways, including IL-6, IL-10, ICAM-1, and tumor necrosis factor α were also measured.Results: Treatment with WY14643 significantly decreased amylase, lipase, myeloperoxidase activity, pathological scores, IL-6, and ICAM-1 levels. The TLR2 and TLR4 mRNA and proteins were markedly decreased after treatment with WY14643, along with IL-6, ICAM-1, and tumor necrosis factor α mRNA levels. However, these effects were completely reversed by the coadministration of MK886.Conclusions: Activation of PPAR-α played a protective role in AP, partially mediated by modulation of TLR pathways.
  •  
39.
  • Ding, Zong-Ling, et al. (författare)
  • Effect of Electrodes on Geometric and Transport Properties of the Graphene-Based Nanomolecular Devices
  • 2011
  • Ingår i: Journal of Nanoscience and Nanotechnology. - : American Scientific Publishers. - 1533-4880 .- 1533-4899. ; 11:12, s. 10778-10781
  • Tidskriftsartikel (refereegranskat)abstract
    • Graphene-based nanomolecular devices are formed by connecting one of the prototype molecular materials of graphene nanoribbons to two Au electrodes. The geometric structure and electronic properties are calculated by using density functional theory. Basing on the optimized structure and the electronic distributions, we obtain the transport properties of the devices by using the Green's functional method. It is found that that the geometry structures of the molecule and the transport properties are sensitive to the distance between source and drain electrodes. With increasing the distances, the curvature radius of the atomic plane is increased, and the deformation energy is decreased. The current versus voltage curves have almost same threshold voltage with different distances between the electrodes. The transmission probability, the density of states and the external bias voltage play important role in determining the transport properties of the molecular devices.
  •  
40.
  • Dominguez, Cecilia A, et al. (författare)
  • Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia
  • 2008
  • Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 136:3, s. 313-319
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1(avl)), Piebald Virol Glaxo (PVG; RT1(c)), and in the major histocompatibility complex (MHC)-congenic strain PVG-RT1(avl). All strains developed mechanical hypersensitivity (allodynia) following nerve injury. However, the extent and duration of allodynia varied significantly among the strains, with PVG displaying more severe allodynia compared to DA rats. Interestingly, the response of PVG-RT1(avR1) was similar to that of DA, suggesting regulation by the MHC locus. This notion was subsequently confirmed in an F2 cohort derived from crossing of the PVG and PVG-RT1(avl) strains, where allodynia was reduced in homozygous or heterozygous carriers of the RT1(avl) allele in comparison to rats homozygous for the RT1(c) allele. These results indicate that certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury in rats.
  •  
41.
  • Doyon, Mélanie, et al. (författare)
  • L’approche Living Lab et l’aménagement des espaces ouverts agricoles. Un exemple en région métropolitaine de Montréal [Living Lab approach and agricultural open space planning. An example in the Montreal metropolitan region]
  • 2015
  • Ingår i: Articulo. - : OpenEdition. - 1661-4941. ; :Special issue 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cet article a pour objet de présenter le travail d’une équipe multidisciplinaire impliquée dans l’élaboration d’une démarche Living Lab visant à dénouer les écueils qui font obstacle à l’aménagement multifonctionnel d’un espace ouvert dans la ville de Longueuil, aux confins de la Communauté métropolitaine de Montréal. Dans un premier temps, nous abordons la démarche Living Lab puis la notion d’espace ouvert. Nous exposons ensuite les principaux enjeux des espaces agricoles dans la région métropolitaine de Montréal, en nous concentrant sur la façon dont l’agglomération de Longueuil a cherché, par le passé, à mettre en valeur ses espaces ouverts dans le cadre d’un projet nommé le Continuum ville-campagne. Enfin, nous décrivons l’amorce d’une démarche de Living Lab pour l’implantation d’un Carrefour d’innovation bioalimentaire. L’article vise ainsi à documenter les premières étapes d’une expérience de Living Lab dans le développement d’un espace ouvert agricole au Québec.
  •  
42.
  • Ellinghaus, David, et al. (författare)
  • Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies
  • 2013
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 145:2, s. 339-347
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies.METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems.RESULTS: We identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 x 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 x 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor kappa B activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways.CONCLUSIONS: We have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD.
  •  
43.
  • Fernández Galván, Ignacio, et al. (författare)
  • S0 → S3 transition in recombination products of photodissociated dihalomethanes
  • 2014
  • Ingår i: Molecular Physics. - : Informa UK Limited. - 0026-8976 .- 1362-3028. ; 112:5-6, s. 575-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Species of the form CH2X–Y (X, Y = Br, I) have been proposed and identified as recombination products of the photodissociation of the parent dihalomethanes. Second-order complete active space perturbation theory (CASPT2) calculations of the vertical absorption energies considerably overestimate the experimental transient absorption band maxima, while the computationally cheaper time-dependent density functional theory (TD-DFT) method yields results with a reasonable agreement. In this work, we try to find the reason for this unexpected performance difference. In an initial study of the I2 molecule, we establish that CASPT2 is capable of providing quantitatively accurate results and that the TD-DFT values are only valid at first sight, but are qualitatively flawed. In the CASPT2 calculations for the CH2X–Y molecules, we include relativistic corrections, spin–orbit coupling, vibrational and thermal effects, and the solvent polarisation. Unfortunately, the results do not improve appreciably compared to the experimental measurements. We conclude that the good agreement of TD-DFT results is very likely fortuitous in this case as well, and that further theoretical and experimental investigations are probably needed to resolve the current discrepancy between CASPT2 and experiments.
  •  
44.
  • Gao, Jingfang, 1966-, et al. (författare)
  • Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations
  • 2007
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:3, s. 345-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The inhibitory proteins, IκBs, regulate the activity of nuclear factor kappa-beta (NF-κB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IκBs may be involved in cancer development through the activation of NF-κB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3′ UTR of NFKBIA (encoding IκBα) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients. Material and methods. A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR-restriction fragment length polymorphism. Results. The frequency of the AG genotype was increased in the Chinese patients ≥50 years of age compared with the Chinese controls (odds ratio (OR) = 3.06, 95% confidence interval (CI) = 1.55-6.02, p=0.001), even when adjusted for age (OR = 3.20, 95% CI = 1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl = 1.28-7.60, p=0.01). Conclusions. Chinese individuals ≥50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients. © 2007 Taylor & Francis.
  •  
45.
  • Gao, Jun, et al. (författare)
  • Coexistence of extended and localized states in finite-sized mosaic Wannier-Stark lattices
  • 2023
  • Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 108:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantum transport and localization are fundamental concepts in condensed matter physics. It is commonly believed that in one-dimensional systems, the existence of mobility edges is highly dependent on disorder. Recently, there has been a debate over the existence of an exact mobility edge in a modulated mosaic model without quenched disorder, the so-called mosaic Wannier-Stark lattice. Here, we experimentally implement such disorder-free mosaic photonic lattices using a silicon photonics platform. By creating a synthetic electric field, we could observe energy-dependent coexistence of both extended and localized states in a finite number of waveguides. The Wannier-Stark ladder emerges when the resulting potential is strong enough, and can be directly probed by exciting different spatial modes of the lattice. Our studies provide the experimental proof of coexisting sets of strongly localized and conducting (though weakly localized) states in finite-sized mosaic Wannier-Stark lattices, which hold the potential to encode high-dimensional quantum resources with compact and robust structures.
  •  
46.
  • Gerami, Majid, et al. (författare)
  • Repair for distributed storage systems with packet erasure channels and dedicated nodes for repair
  • 2016
  • Ingår i: IEEE Transactions on Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0090-6778 .- 1558-0857. ; 64:4, s. 1367-1383
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the repair problem in distributed storage systems where storage nodes are connected through packet erasure channels and some nodes are dedicated to repair [termed as dedicated-for-repair (DR) storage nodes]. We first investigate the minimum required repair-bandwidth in an asymptotic setup, in which the stored file is assumed to have an infinite size. The result shows that the asymptotic repair-bandwidth over packet erasure channels with a fixed erasure probability has a closed-form relation to the repair-bandwidth in lossless networks. Next, we show the benefits of DR storage nodes in reducing the repair bandwidth, and then we derive the necessary minimal storage space of DR storage nodes. Finally, we study the repair in a nonasymptotic setup, where the stored file size is finite. We study the minimum practical-repair-bandwidth, i.e., the repair-bandwidth for achieving a given probability of successful repair. A combinatorial optimization problem is formulated to provide the optimal practical-repair-bandwidth for a given packet erasure probability. We show the gain of our proposed approaches in reducing the repair-bandwidth.
  •  
47.
  • Guo, Xiao-Hua, et al. (författare)
  • Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells
  • 2006
  • Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 114:12, s. 874-883
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.
  •  
48.
  • He, Lu-Jun, et al. (författare)
  • Genetic polymorphisms of N-acetyltransferase 2 and colorectal cancer risk.
  • 2005
  • Ingår i: World Journal of Gastroenterology. - 1007-9327 .- 2219-2840. ; 11:27, s. 4268-4271
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To identify the distribution of N-acetyltrasferase 2(NAT2) polymorphism in Hebei Han Chinese and the effects of the polymorphism on the development of colorectal cancer. METHODS: We performed a hospital-based case-control study of 237 healthy individuals and 83 colorectal cancer patients of Hebei Han Chinese. DNA was extracted from peripheral blood and cancer tissues. The genotypes of the polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP). RESULTS: There were four NAT2 alleles of WT, M1, M2, and M3 both in the healthy subjects and in the patients, and 10 genotypes of WT/WT, WT/M1, WT/M2, WT/M3, M1/M1, M1/M2, M1/M3, M2/M2, M2/M3, M3/M3. M2 allele was present in 15.61% of healthy subjects and 29.52% of patients (chi(2) = 15.31, P<0.0001), and M3 allele was present in 30.59% of healthy subjects and 16.87% of patients (chi(2) = 25.33, P<0.0001). There were more WT/M2 (chi(2) = 34.42, P<0.0001, odd ratio = 4.99, 95%CI = 2.27-9.38) and less WT/M3 (chi(2) = 3.80, P = 0.03) in the patients than in the healthy subjects. In 70.3% of the patients, there was a difference in NAT2 genotype between their tumors and blood cells. Patients had more WT/M2 (chi(2) = 5.11, P = 0.02) and less M2/M3 (chi(2) = 4.27, P = 0.039) in their blood cells than in the tumors. Furthermore, 53.8% (7/13) of M2/M3 in tumors were from WT/M2 of blood cells. CONCLUSION: There is a possible relationship between the NAT2 polymorphisms and colorectal cancer in Hebei Han Chinese. The genotype WT/M2 may be a risk factor for colorectal cancer.
  •  
49.
  • Huang, Juan, et al. (författare)
  • Differential metabolic profiles of ginsenosides in artificial gastric juice using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry
  • 2022
  • Ingår i: BMC Biomedical chromotography. - : John Wiley & Sons. - 0269-3879 .- 1099-0801. ; 36:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Ginsenosides have poor oral bioavailability and undergo rapid biological transformation in the complex gastrointestinal environment. Most studies on the metabolism of ginsenosides have focused on gut bacteria, yet gastric juice remains a nonnegligible factor. Metabolic profiles of ginsenoside monomers formed in artificial gastric juice were separately investigated and qualitatively identified using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn). A common pattern of their metabolic pathways was established, showing that ginsenosides were transformed via deglycosylation, hydration, and dehydration pathways. Two major structure types, 20(S), 20(R)-protopanaxatriols and 20(S), 20(R)-protopanaxadiols, basically shared similar transformation pathways and yielded deglycosylated, hydrated, and dehydrated products. Fragmentation patterns of major ginsenosides were also discussed. Consequently, gastric juice, as the primary link in ginsenoside metabolism and as important as the intestinal flora, produces considerable amounts of degraded ginsenosides, providing a partial explanation for the low bioavailabilities of primary ginsenosides.
  •  
50.
  • Huang, Shoushuang, et al. (författare)
  • Amorphous and defective Co-P-O@NC ball-in-ball hollow structure for highly efficient electrocatalytic overall water splitting
  • 2023
  • Ingår i: Journal of Colloid and Interface Science. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0021-9797 .- 1095-7103. ; 649, s. 1047-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrochemical water splitting using hollow and defect-rich catalysts has emerged as a promising strategy for efficient hydrogen production. However, the rational design and controllable synthesis of such catalysts with intricate morphology and composition present significant challenges. Herein, we propose a template-engaged approach to fabricate a novel ball-in-ball hollow structure of Co-P-O@N-doped carbon with abundant oxygen vacancies. The synthesis process involves the preparation of uniform cobalt-glycerate (Co-gly) polymer microspheres as precursors, followed by surface coating with ZIF-67 layer, adjustable chemical etching by phytic acid, and controllable pyrolysis at high temperature. The resulting ball-in-ball structure offers a large number of accessible active sites and high redox reaction centers, facilitating efficient charge transport, mass transfer, and gas evolution, which are beneficial for the acceleration of electrocatalytic reaction. Additionally, density functional theory (DFT) calculations indicate that the incorporation of oxygen and the presence of Co-P dangling bonds in CoP significantly enhance the adsorption of oxygenated species, leading to improved intrinsic electroactivity at the single-site level. As a sequence, the titled catalyst exhibits remarkable electrocatalytic activity and stability for water splitting in alkaline media. Notably, it only requires a low overpotential of 283 mV to achieve a current density of 10 mA cm-2 for the oxygen evolution reaction. This work may provide some new insights into the design of complex hollow structures of phosphides with abundant defects for energy conversion.
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