| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)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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| 2. |
- Jin, Ying-Hui, et al.
(author)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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In: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Journal article (peer-reviewed)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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| 3. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
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| 6. |
- Leebens-Mack, James H., et al.
(author)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Journal article (peer-reviewed)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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| 7. |
- Pecunia, Vincenzo, et al.
(author)
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Roadmap on energy harvesting materials
- 2023
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In: Journal of Physics. - : IOP Publishing. - 2515-7639. ; 6:4
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Journal article (peer-reviewed)abstract
- Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.
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| 8. |
- Lin, Qing, et al.
(author)
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Mechanistic and therapeutic study of novel anti-tumor function of natural compound imperialine for treating non-small cell lung cancer
- 2020
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In: Journal of Ethnopharmacology. - : Elsevier. - 0378-8741 .- 1872-7573. ; 247
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Journal article (peer-reviewed)abstract
- Ethnopharmacological relevance: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. Aim of the study: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. Materials and methods: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. Results: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-kappa B activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. Conclusions: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-kappa B centered inflammation-cancer feedback loop. Imperialine mediated anticancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.
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| 9. |
- Liu, Yongkui, et al.
(author)
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A framework for scheduling in cloud manufacturing with deep reinforcement learning
- 2019
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In: 2019 IEEE 17th International Conference on Industrial Informatics Aalto University (INDIN). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 1775-1780
-
Conference paper (peer-reviewed)abstract
- Cloud manufacturing is a novel service-oriented networked manufacturing paradigm that aims to provide on-demand manufacturing cloud services to consumers. Scheduling is a critical means for achieving that aim. Currently, research on scheduling in cloud manufacturing is still in its infancy, and current frequently adopted meta-heuristic algorithm-based approaches have some shortcomings, e.g. they require complex design processes and lack adaptability to dynamic environments. Deep reinforcement learning (DRL) that combines advantages of reinforcement learning and deep learning provides an efficient, adaptive and intelligent approach for solving scheduling problems in cloud manufacturing. However, to the best of our knowledge, there has been no application of DRL to scheduling in cloud manufacturing. This work conducts a preliminary exploration over this issue. First, a DRL-based framework for scheduling in cloud manufacturing is proposed. Then a DRL model for online single-task scheduling in cloud manufacturing is presented to demonstrate the effectiveness of the framework. DRL as a promising technique will find wide applications in cloud manufacturing, and this work can provide some reference for future research on this.
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| 10. |
- Liu, Yongkui, et al.
(author)
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Cloud manufacturing : key issues and future perspectives
- 2019
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In: International journal of computer integrated manufacturing (Print). - : Taylor & Francis. - 0951-192X .- 1362-3052. ; 32:9, s. 858-874
-
Journal article (peer-reviewed)abstract
- Since the introduction of the concept of cloud manufacturing in 2010, research on it has been ongoing for more than eight years, and much progress has been made. However, existing research indicates that people lack common and comprehensive understandings of some of the key issues with cloud manufacturing such as the concept, operation model, service mode, technology system, architecture, and essential characteristics. Moreover, few studies discuss in depth the relationships between cloud manufacturing and some closely related concepts such as cloud computing-based manufacturing, Cyber-Physical Systems (CPS), smart manufacturing, Industry 4.0, and Industrial Internet. Knowledge as a core supporting factor in cloud manufacturing has rarely been discussed systematically. Also, so far there has been no standardised definition for cloud manufacturing yet. All these are key issues to be further discussed and analysed in cloud manufacturing. In order to clarify the issues above and provide reference for future research and implementation, this paper conducts a comprehensive, systematic, and in-depth discussion and analysis of the aforementioned issues in cloud manufacturing and presents an alternative definition for cloud manufacturing based on the analysis of 12 existing definitions. Future perspectives of cloud manufacturing are also discussed with respect to both academic research and industrial implementation.
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| 11. |
- Liu, Yongkui, et al.
(author)
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Industrial Internet for Manufacturing
- 2021
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In: Robotics and Computer-Integrated Manufacturing. - : Elsevier BV. - 0736-5845 .- 1879-2537. ; 70
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Journal article (other academic/artistic)
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| 12. |
- Liu, Yongkui, et al.
(author)
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Scheduling in cloud manufacturing : state-of-the-art and research challenges
- 2019
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In: International Journal of Production Research. - : TAYLOR & FRANCIS LTD. - 0020-7543 .- 1366-588X. ; 57:15-16, s. 4854-4879
-
Research review (peer-reviewed)abstract
- For the past eight years, cloud manufacturing as a new manufacturing paradigm has attracted a large amount of research interest worldwide. The aim of cloud manufacturing is to deliver on-demand manufacturing services to consumers over the Internet. Scheduling is one of the critical means for achieving the aim of cloud manufacturing. Thus far, about 158 articles have been published on scheduling in cloud manufacturing. However, research on scheduling in cloud manufacturing faces numerous challenges. Thus, there is an urgent need to ascertain the current status and identify issues and challenges to be addressed in the future. Covering articles published on the subject over the past eight years, this article aims to provide a state-of-the-art literature survey on scheduling issues in cloud manufacturing. A detailed statistical analysis of the literature is provided based on the data gathered from the Elsevier's Scopus abstract and citation database. Typical characteristics of scheduling issues in cloud manufacturing are systematically summarised. A comparative analysis of scheduling issues in cloud manufacturing and other scheduling issues such as cloud computing scheduling, workshop scheduling and supply chain scheduling is also carried out. Finally, future research issues and challenges are identified.
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| 13. |
- Qin, Haihong, et al.
(author)
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Switching Time Delay Optimization for “SiC+Si” Hybrid Device in a Phase-leg Configuration
- 2021
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In: IEEE Access. - 2169-3536 .- 2169-3536. ; 9, s. 37542-37556
-
Journal article (peer-reviewed)abstract
- Compared to SiC MOSFET, the switching loss of Si IGBT is much higher due to its slow switching speed and tail current. Si IGBT/SiC MOSFET hybrid switch device can reach to optimal performance with low static and dynamic loss, which can improve the current capacity of SiC devices and reduce the power loss of Si IGBT based converters. With the separated gate control signals, the switching moments of the two devices can be controlled independently to ensure Si IGBT under zero-voltage switching (ZVS) conditions. This measurement tends to reduce the switching loss of Si IGBT. However, the switching time delay between these two devices has significant impacts on its power loss. In this paper, the switching time delay optimization method is proposed to minimize the power loss of the hybrid switch. The static and dynamic characteristics of Si IGBT/SiC MOSFET hybrid-paralleled switch are studied, and a generalized power loss model for hybrid switch is developed. The influence of switching time delay on the characteristics of hybrid switch is analyzed and verified through double pulse tests in a phase-leg configuration. The experimental results show that the optimal turn-on delay time is that the two devices turn on at the same time and the turn-on loss can be reduced by about 73% compared with the solely Si IGBT and by about 52% compared with the solely SiC MOSFET. While the optimal turn-off sequence is that the Si IGBT turns off ahead of the SiC MOSFET. Under the proposed optimal turn-off delay time of the hybrid switch, the turn-off loss is reduced by about 61.4%. This optimization strategy is used in a Buck converter to verify the superiority of the SiC/Si hybrid switch and the optimal switching sequence. Simulation results show that the optimal switching sequence is consistent with theoretical analysis, and the efficiency is improved by 2.5% compared with Buck converter using solely Si IGBT.
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| 14. |
- Tang, Feng, et al.
(author)
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Eoandromeda and the origin of Ctenophora.
- 2011
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In: Evolution & Development. - 1520-541X .- 1525-142X. ; 13:5, s. 408-414
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Journal article (peer-reviewed)abstract
- The Ediacaran fossil Eoandromeda octobrachiata had a high conical body with eight arms in helicospiral arrangement along the flanks. The arms carried transverse bands proposed to be homologous to ctenophore ctenes (comb plates). Eoandromeda is interpreted as an early stem-group ctenophore, characterized by the synapomorphies ctenes, comb rows, and octoradial symmetry but lacking crown-group synapomorphies such as tentacles, statoliths, polar fields, and biradial symmetry. It probably had a pelagic mode of life. The early appearance in the fossil record of octoradial ctenophores is most consistent with the Planulozoa hypothesis (Ctenophora is the sister group of Cnidaria + Bilateria) of metazoan phylogeny.
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| 15. |
- Wang, Fei, et al.
(author)
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Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-beta, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.
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| 16. |
- Wang, Jinlei, et al.
(author)
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Development of wireless specific mosquito counter by optical technology
- 2018
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In: 2018 Asia Communications and Photonics Conference, ACP 2018. - 9781538661581 ; 2018-October
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Conference paper (peer-reviewed)abstract
- Mosquitoes carry malaria and dengue fever and constitute a great threat to public health. We develop a wireless mosquito counting device which can provide valuable statistic information.
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| 17. |
- Wang, Xun, et al.
(author)
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Achieving Capital Account Convertibility in China
- 2011
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In: China Economic Journal. - : Taylor & Francis (Routledge): SSH Titles. - 1753-8971 .- 1753-8963. ; 4:1, s. 25-42
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Journal article (peer-reviewed)abstract
- China has been delaying the plan of achieving capital account convertibility since the Asian financial crisis, although restrictions on capital flows have been reduced steadily, confirmed by the falling Capital Account Control Index. Current restrictions exist mainly for cross-border portfolio investment, debt financing and outward direct investment (ODI). Effectiveness of these restrictions, however, has been declining over time. While capital controls probably helped support domestic financial stability in the past, their potential costs are rising quickly, evidenced by losing independence of the monetary policy. China already possesses a range of favorable conditions for capital account liberalization, including stable macroeconomic situation, healthy fiscal and financial systems, and strong external accounts. Some of these conditions may be reversed in the coming years. Therefore, China should probably try to achieve basic capital account convertibility within the next three to five years. This requires, among others, establishment of market-based interest rates and exchange rates. The authorities could probably remove restrictions on debt financing and ODI quickly. For the more volatile portfolio investment, they could retain the existing qualified foreign institutional investor and qualified domestic institutional investor schemes, with significantly increased quotas but substantially reduced restrictions during the transition period.
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| 18. |
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| 19. |
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| 20. |
- Yu, Xin, et al.
(author)
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Piezoelectric Effect Modulates Nanozyme Activity: Underlying Mechanism and Practical Application
- 2023
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In: Small. - 1613-6810 .- 1613-6829. ; 19:52
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Research review (peer-reviewed)abstract
- Nanozyme activity relies on surface electron transfer processes. Notably, the piezoelectric effect plays a vital role in influencing nanozyme activity by generating positive and negative charges on piezoelectric materials' surfaces. This article comprehensively reviews the potential mechanisms and practical applications of regulating nanozyme activity through the piezoelectric effect. The article first elucidates how the piezoelectric effect enables nanozymes to exhibit catalytic activity. It is highlighted that the positive and negative charges produced by this effect directly participate in redox reactions, leading to the conversion of materials from an inactive to an active state. Moreover, the piezoelectric field generated can enhance nanozyme activity by accelerating electron transfer rates or reducing binding energy between nanozymes and substrates. Practical applications of piezoelectric nanozymes are explored in the subsequent section, including water pollutant degradation, bacterial disinfection, biological detection, and tumor therapy, which demonstrate the versatile potentials of the piezoelectric effect in nanozyme applications. The review concludes by emphasizing the need for further research into the catalytic mechanisms of piezoelectric nanozymes, suggesting expanding the scope of catalytic types and exploring new application areas. Furthermore, the promising direction of synergistic catalytic therapy is discussed as an inspiring avenue for future research.
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| 21. |
- Zhao, Zhiqi, et al.
(author)
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Analysis of enhanced turbulent heat transfer in a sharp turn channel having novel designed endwall with longitudinal vortex generator
- 2022
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In: International Communications in Heat and Mass Transfer. - : Elsevier BV. - 0735-1933. ; 131
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Journal article (peer-reviewed)abstract
- This work provides a new method to enhance endwall heat transfer of a sharp turn channel. Several longitudinal vortex generators (LVGs) at various spacing and aspect ratio are placed in parallel on the inner side of endwall in a sharp turn channel. Liquid crystal thermography, pressure difference measurements, and a statistical method are applied to analyze the thermal behavior, friction factor, and temperature uniformity on the endwall mounted with an array of LVGs. The Reynolds number are in the range of 10,000 to 20,000. A comparison between the novel designed endwall and conventional turbulators in the same U bend channel is also conducted. Results indicate that the local Nusselt number is greatly augmented with the application of LVGs on the endwall, especially at the downstream part of the endwall. The LVGs with an aspect ratio of 2 and a spacing of 20 mm (dense case) provides the optimal thermal characteristics. The optimal design provides augmentation of heat transfer rate and thermal performance factor by up to 35.1% and 25.5%, respectively. The endwall fitted with delta-winglet vortex generators is a promising enhanced heat transfer method compared with the conventional design available for the same U-duct model.
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| 22. |
- Zhou, Weibin, et al.
(author)
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Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension
- 2022
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 146:24, s. 1855-1881
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Journal article (peer-reviewed)abstract
- Background:Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. Methods:VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 (Vefgr2(Y949F)) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure. Results:We show that PH leads to excessive pulmonary vascular leak in both patients and hypoxic mice, and this is because of an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In the context of hypoxic PH, activation of Yes1 and c-Src and subsequent VE-cadherin phosphorylation in endothelial cells are involved in VEGFR2 Y949-induced vascular permeability. Abolishing VEGFR2 Y949 signaling by Vefgr2(Y949F) point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure, thereby leading to alleviated PH manifestations, including muscularization of distal pulmonary arterioles, elevated right ventricle systolic pressure, and right ventricular hypertrophy. It is important that we found that VEGFR2 Y949 signaling in myeloid cells including macrophages was trivial and dispensable for hypoxia-induced vascular abnormalities and PH. In contrast with selective blockage of VEGFR2 Y949 signaling, disruption of the entire VEGFR2 signaling by conditional endothelial deletion of Vegfr2 promotes the development of PH. Conclusions:Our results support the notion that VEGF-A/VEGFR2 Y949-dependent vascular permeability is an important determinant in the pathogenesis of PH and might serve as an attractive therapeutic target pathway for this disease.
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| 23. |
- Beelen, Rob, et al.
(author)
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Effects of long-term exposure to air pollution on natural-cause mortality : an analysis of 22 European cohorts within the multicentre ESCAPE project
- 2014
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 383:9919, s. 785-795
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Journal article (peer-reviewed)abstract
- Background Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. Methods We used data from 22 European cohort studies, which created a total study population of 367 251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and between 10 mu m and 2.5 mu m (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buff er. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. Findings The total study population consisted of 367 251 participants who contributed 5 118 039 person-years at risk (average follow-up 13.9 years), of whom 29 076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 mu g/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I-2 p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 mu g/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 mu g/m(3) (1.07, 1.01-1.13). Interpretation Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value.
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| 24. |
- Beelen, Rob, et al.
(author)
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Long-term Exposure to Air Pollution and Cardiovascular Mortality An Analysis of 22 European Cohorts
- 2014
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In: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:3, s. 368-378
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Journal article (peer-reviewed)abstract
- Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and 10 mu m to 2.5 mu m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 mu g/m(3) and for PM10, 1.22 (0.91-1.63) per 10 mu g/m(3). Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
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| 25. |
- Beelen, Rob, et al.
(author)
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Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
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Research review (peer-reviewed)abstract
- Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
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