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2.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)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.
  • An, Feng-Wei, et al. (author)
  • Establishment of a Large Animal Model for Eustachian Tube Functional Study in Miniature Pigs
  • 2019
  • In: Anatomical Record Part A-discoveries in Molecular Cellular and Evolutionary Biology. - : WILEY. - 1552-4884 .- 1932-8494. ; 302:6, s. 1024-1038
  • Journal article (peer-reviewed)abstract
    • This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study. 
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4.
  • An, Junghwa, et al. (author)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
  • 2010
  • In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
  • Journal article (peer-reviewed)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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5.
  • Guo, Hui-Hui, et al. (author)
  • Alleviation of allergic asthma by rosmarinic acid via gut-lung axis
  • 2024
  • In: Phytomedicine. - : Elsevier. - 0944-7113 .- 1618-095X. ; 126
  • Journal article (peer-reviewed)abstract
    • Background: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NF kappa B mediated pulmonary inflammation and oxidative stress. Conclusions: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiotaderived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
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6.
  • Hu, Hai-Xi, et al. (author)
  • Structural insights into HetR-PatS interaction involved in cyanobacterial pattern formation
  • 2015
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
  • Journal article (peer-reviewed)abstract
    • The one-dimensional pattern of heterocyst in the model cyanobacterium Anabaena sp. PCC 7120 is coordinated by the transcription factor HetR and PatS peptide. Here we report the complex structures of HetR binding to DNA, and its hood domain (HetR(Hood)) binding to a PatS-derived hexapeptide (PatS6) at 2.80 and 2.10 angstrom, respectively. The intertwined HetR dimer possesses a couple of novel HTH motifs, each of which consists of two canonical alpha-helices in the DNA-binding domain and an auxiliary alpha-helix from the flap domain of the neighboring subunit. Two PatS6 peptides bind to the lateral clefts of HetR(Hood), and trigger significant conformational changes of the flap domain, resulting in dissociation of the auxiliary alpha-helix and eventually release of HetR from the DNA major grove. These findings provide the structural insights into a prokaryotic example of Turing model.
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7.
  • Jin, Ying-Hui, et al. (author)
  • Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
  • 2020
  • In: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
  • 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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  • Proletov, Ian, et al. (author)
  • Primary and secondary glomerulonephritides 1.
  • 2014
  • In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
  • Journal article (peer-reviewed)
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  • 2019
  • Journal article (peer-reviewed)
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  • An, De-Wei, et al. (author)
  • Carotid-Femoral Pulse Transit Time Variability Predicted Mortality and Improved Risk Stratification in the Elderly
  • 2021
  • In: Hypertension. - 1524-4563. ; 78:5, s. 1287-1295
  • Journal article (peer-reviewed)abstract
    • The carotid-to-femoral pulse wave velocity, determined by pulse transit time (PTT) and distance, is a well-established measure of arterial stiffness and predicts adverse outcomes. However, its predictive value decreases with aging. To explore new risk indicator in the elderly, we investigated if the variation of carotid-to-femoral pulse wave velocity, registered as beat-to-beat variability of carotid-to-femoral PTT (cf-PTT), could predict outcome. Totally 3015 (median age, 72.4 years; 39.6% men) and 1181 (75.6 years; 42.2% men) subjects from communities of Malmö, Sweden, and Shanghai, China, were analyzed, respectively. Continuous pulse waves for 10 seconds were recorded sequentially at carotid and femoral arterial sites with applanation tonometry (SphygmoCor, Atcor, Australia). During a median of 6.6 and 10.2 years, 389 and 427 deaths occurred in the Malmö and Shanghai cohorts, respectively. Each one-SD increase in the log-transformed coefficient of variation of cf-PTT was associated with 24% (95% CI, 13%–37%) and 21% (10%–33%) increased risk for all-cause mortality in the Malmö and Shanghai subjects, and 60% (33%–91%) for cardiovascular mortality in the Malmö subjects. Adding the coefficient of variation of cf-PTT to the models including conventional risk factors and carotid-to-femoral pulse wave velocity significantly (P<0.05) improved prediction for all-cause mortality in both cohorts (integrated discrimination improvement, 0.005–0.008) and cardiovascular mortality in the Malmö cohort (net reclassification improvement, 0.206). In both cohorts, a coefficient of variation of cf-PTT <6% was not associated with increased mortality risk. In conclusion, the beat-to-beat variability of cf-PTT predicted mortality and improved risk stratification, which might be a novel risk indicator for elderly people.
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  • Cai, Chuner, et al. (author)
  • Screening and verification of extranuclear genetic markers in green tide algae from the Yellow Sea : Extranuclear markers in green tide algae
  • 2021
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6
  • Journal article (peer-reviewed)abstract
    • Over the past decade, Ulva compressa, a cosmopolitan green algal species, has been identified as a component of green tides in the Yellow Sea, China. In the present study, we sequenced and annotated the complete chloroplast genome of U. compressa (alpha-numeric code: RD9023) and focused on the assessment of genome length, homology, gene order and direction, intron size, selection strength, and substitution rate. We compared the chloroplast genome with the mitogenome. The generated phylogenetic tree was analyzed based on single and aligned genes in the chloroplast genome of Ulva compared to mitogenome genes to detect evolutionary trends. U. compressa and U. mutabilis chloroplast genomes had similar gene queues, with individual genes exhibiting high homology levels. Chloroplast genomes were clustered together in the entire phylogenetic tree and shared several forward/palindromic/tandem repetitions, similar to those in U. prolifera and U. linza. However, U. fasciata and U. ohnoi were more divergent, especially in sharing complementary/palindromic repetitions. In addition, phylogenetic analyses of the aligned genes from their chloroplast genomes and mitogenomes confirmed the evolutionary trends of the extranuclear genomes. From phylogenetic analysis, we identified the petA chloroplast genes as potential genetic markers that are similar to the tufA marker. Complementary/forward/palindromic interval repetitions were more abundant in chloroplast genomes than in mitogenomes. Interestingly, a few tandem repetitions were significant for some Ulva subspecies and relatively more evident in mitochondria than in chloroplasts. Finally, the tandem repetition [GAAATATATAATAATA × 3, abbreviated as TRg)] was identified in the mitogenome of U. compressa and the conspecific strain U. mutabilis but not in other algal species of the Yellow Sea. Owing to the high morphological plasticity of U. compressa, the findings of this study have implications for the rapid non-sequencing detection of this species during the occurrence of green tides in the region.
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  • Cai, Yumeng, et al. (author)
  • Characterization of Gate-Oxide Degradation Location for SiC MOSFETs Based on the Split C-V Method Under Bias Temperature Instability Conditions
  • 2023
  • In: IEEE transactions on power electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 0885-8993 .- 1941-0107. ; 38:5, s. 6081-6093
  • Journal article (peer-reviewed)abstract
    • Gate-oxide degradation has been one of the major reliability challenges of SiC mosfets. Comprehensive and accurate localization of gate-oxide degradation under bias temperature instability (BTI) conditions is important to improve the device reliability. The split C-V [gate-source capacitance C-GS (v(G)) and gate-drain capacitance C-GD (v(G))] method is proposed in this article to locate gate-oxide degradation. Moreover, a BTI automated characterization system integrated I-V and split C-V test is presented. The effect of gate-oxide degradation on threshold voltage and split C-V under dc and ac BTI conditions is investigated and the degradation location is analyzed. Furthermore, the degradation simulation is conducted with technology computer aided design (TCAD) to reveal the mechanism. The results show that the different parts of split C-V can characterize degradation location, the type, and energy level of traps. The acceptor traps near valence band and donor traps near conduction band cause gate-oxide degradation above the channel and junction field effect transistor (JFET) region in positive bias temperature instability (PBTI) and Negative Bias Temperature Instability (NBTI), respectively. In ac BTI, the gate-oxide degradation at the channel region is independent of v(G) polarity, while the opposite is true above JFET region. These findings help to improve the long-term operation reliability of gate oxide from the perspective of chip design and application.
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  • Cong, Rihua, et al. (author)
  • Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene
  • 2020
  • In: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 59:6, s. 2497-2506
  • Journal article (peer-reviewed)abstract
    • PurposeThe aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring.MethodsFourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP).ResultsHigh-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed.ConclusionsTaken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.
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  • Esteban, Pablo G., et al. (author)
  • How to Build a Supervised Autonomous System for Robot-Enhanced Therapy for Children with Autism Spectrum Disorder
  • 2017
  • In: Paladyn - Journal of Behavioral Robotics. - : De Gruyter Open. - 2080-9778 .- 2081-4836. ; 8:1, s. 18-38
  • Journal article (peer-reviewed)abstract
    • Robot-Assisted Therapy (RAT) has successfully been used to improve social skills in children with autism spectrum disorders (ASD) through remote control of the robot in so-called Wizard of Oz (WoZ) paradigms.However, there is a need to increase the autonomy of the robot both to lighten the burden on human therapists (who have to remain in control and, importantly, supervise the robot) and to provide a consistent therapeutic experience. This paper seeks to provide insight into increasing the autonomy level of social robots in therapy to move beyond WoZ. With the final aim of improved human-human social interaction for the children, this multidisciplinary research seeks to facilitate the use of social robots as tools in clinical situations by addressing the challenge of increasing robot autonomy.We introduce the clinical framework in which the developments are tested, alongside initial data obtained from patients in a first phase of the project using a WoZ set-up mimicking the targeted supervised-autonomy behaviour. We further describe the implemented system architecture capable of providing the robot with supervised autonomy.
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  • Feng, Lei, et al. (author)
  • Tea Consumption and Depressive Symptoms in Older People in Rural China
  • 2013
  • In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 61:11, s. 1943-1947
  • Journal article (peer-reviewed)abstract
    • ObjectivesTo examine the association between tea consumption and depressive symptoms in Chinese older people and to explore the mediating role of cerebrovascular disease in the association. DesignPopulation-based cross-sectional study. SettingA rural community near Qufu in Shandong, China. ParticipantsCommunity-dwelling individuals aged 60 and older (mean 68.6; 59.3% female) from the Confucius Hometown Aging Project (N=1,368). MeasurmentsData were collected through interviews, clinical examinations, and psychological testing, following a standard procedure. Presence of high depressive symptoms was defined as a score of 5 or greater on the 15-item Geriatric Depression Scale. ResultsOf the 1,368 participants, 165 (12.1%) were weekly and 489 (35.7%) were daily tea consumers. Compared with no or irregular tea consumption, controlling for age, sex, education, leisure activities, number of comorbidities, and Mini-Mental State Examination score, the odds ratios of having high depressive symptoms were 0.86 (95% confidence interval (CI)=0.56-1.32) for weekly and 0.59 (95% CI=0.43-0.81) for daily tea consumption (P for linear trend=.001); the linear trend of the association remained statistically significant when further controlling for history of stroke, transient ischemic attacks, and presence of carotid plaques. ConclusionsDaily tea consumption is associated with a lower likelihood of depressive symptoms in Chinese older people living in a rural community. The association appears to be independent of cerebrovascular disease and atherosclerosis.
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  • Haas, Brian J., et al. (author)
  • Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
  • 2009
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
  • Journal article (peer-reviewed)abstract
    • Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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  • Jarvis, Erich D., et al. (author)
  • Whole-genome analyses resolve early branches in the tree of life of modern birds
  • 2014
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
  • Journal article (peer-reviewed)abstract
    • To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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24.
  • Kanoni, Stavroula, et al. (author)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Journal article (peer-reviewed)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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  • Kato, Norihiro, et al. (author)
  • Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
  • 2015
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
  • Journal article (peer-reviewed)abstract
    • We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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  • Lam, BYK, et al. (author)
  • The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis
  • 2023
  • In: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 18:1, s. 15-27
  • Journal article (peer-reviewed)abstract
    • Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. Aim: This study aims to systematically review the prevalence of cSVD in LMICs. Results: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3–80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. Conclusions: This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.
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28.
  • Li, Yaohui, et al. (author)
  • An n-n Heterojunction Configuration for Efficient Electron Transport in Organic Photovoltaic Devices
  • 2023
  • In: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028. ; 33:9
  • Journal article (peer-reviewed)abstract
    • Selective electron transport and extraction are essential to the operation of photovoltaic devices. Electron transport layer (ETL) is therefore critical to organic photovoltaics (OPV). Herein, an ETL configuration is presented comprising a solution-processed n-n organic heterojunction to enhance electron transport and hole blocking, and boost power conversion efficiency (PCE) in OPV. Specifically, the n-n heterojunction is constructed by stacking a narrow-band n-type conjugated polymer layer (PNDIT-F3N) and a wide-band n-type conjugated molecule layer (Phen-NaDPO). Based on the ultraviolet photoelectron spectroscopy measurement and numerical simulation of current density-voltage characteristics, the formation of the built-in potential is investigated. In three OPVs with different active layers, substantial improvements are observed in performance following the introduction of this ETL configuration. The performance enhancement arises from the combination of selective carrier transport properties and reduced recombination. Another contributing factor is the good film-forming quality of the new ETL configuration, where the surface energies of the related materials are well-matched. The n-n organic heterojunction represents a viable and promising ETL construction strategy for efficient OPV devices.
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29.
  • Liang, Jianxin, et al. (author)
  • Mechanistic study of transcription factor Sox18 during heart development
  • 2024
  • In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 350
  • Journal article (peer-reviewed)abstract
    • Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.
  •  
30.
  • Liang, Yajun, et al. (author)
  • Association Between Lipid Profile and Depressive Symptoms Among Chinese Older People : Mediation by Cardiovascular Diseases?
  • 2014
  • In: International Journal of Behavioral Medicine. - : Springer Science and Business Media LLC. - 1070-5503 .- 1532-7558. ; 21:4, s. 590-596
  • Journal article (peer-reviewed)abstract
    • The potential mediating effect of cardiovascular diseases (CVDs) (e.g., ischemic heart disease and stroke) on the association between abnormal serum lipids and late-life depressive symptoms has not been investigated. We aimed to examine the associations between serum lipids and elevated depressive symptoms among older Chinese people and to determine the extent to which CVDs mediate their associations. This cross-sectional study included 1,529 participants (age a parts per thousand yen60 years, 59.2 % women) in the Confucius Hometown Aging Project. In June 2010-July 2011, data were collected through an interview, clinical examinations, and laboratory tests. Abnormal serum lipids were defined according to international criteria and use of hypolipidemic drugs. Presence of elevated depressive symptoms was defined as the 15-item Geriatric Depression Scale score a parts per thousand yen5. Data were analyzed with logistic and mediation models controlling for potential confounders. The prevalence of depressive symptoms was 20.3 %. Depressive symptomatology was significantly associated with high total cholesterol, high triglycerides, low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol (LDL-C), and dyslipidemia (p < 0.05). The mediating effects on the associations of serum lipids with depressive symptoms were statistically significant for ischemic heart disease and stroke with the proportion of mediating effects over the total effects ranging 4.7-7.0 % and 7.3-12.1 %, respectively. Elevated depressive symptoms are associated with lipid profile characterized by high cholesterol, high triglycerides, low HDL-C, high LDL-C, and dyslipidemia; the associations are partially mediated by ischemic heart disease and stroke. These findings imply that unfavorable lipid profile may be involved in late-life depressive symptoms independent of atherosclerotic disorders.
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31.
  • Liang, Yajun, et al. (author)
  • Cardiovascular Risk Factor Profiles for Peripheral Artery Disease and Carotid Atherosclerosis among Chinese Older People : A Population-Based Study
  • 2014
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e85927-
  • Journal article (peer-reviewed)abstract
    • Objectives: Epidemiological data concerning atherosclerotic disease among older people in rural China are sparse. We seek to determine prevalence and cardiovascular risk factor profiles for peripheral artery disease (PAD) and carotid atherosclerosis (CAS) among Chinese older people living in a rural community. Methods: This cross-sectional study included 1499 participants (age >= 60 years, 59.0% women) of the Confucius Hometown Aging Project in Shandong, China. From June 2010-July 2011, data were collected through interviews, clinical examinations, and laboratory tests. PAD was defined as an ankle-brachial index <= 0.9. Carotid intima-media thickness (cIMT) and carotid artery stenosis were assessed by ultrasonography. We defined moderate stenosis as carotid stenosis >= 50%, and severe stenosis as carotid stenosis >= 70%. cIMT >= 1.81 mm was considered as an increased cIMT (a measure of CAS). Data were analyzed with multiple logistic models. Results: The prevalence was 5.7% for PAD, 8.9% for moderate stenosis, 1.8% for severe stenosis, and 11.2% for increased cIMT. After controlling for multiple potential confounders, diabetes, an increased low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, and hypertension were significantly or marginally associated with PAD. Ever smoking, hypertension, and an increased LDL-C/HDL-C ratio were significantly associated with an increased likelihood of increased cIMT. An increasing number of those cardiovascular risk factors were significantly associated with an increasing odds ratio of PAD and increased cIMT, respectively (p for linear trend < 0.001). Conclusion: Among Chinese older people living in a rural community, PAD, carotid artery stenosis, and an increased cIMT are relatively uncommon. Cardiovascular risk factor profiles for PAD and CAS are slightly different, with hypertension and an increased LDL-C/HDL-C ratio being associated with an increased likelihood of both PAD and increased cIMT.
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32.
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33.
  • Liang, Yajun, et al. (author)
  • Use of medications and functional dependence among Chinese older adults in a rural community : A population-based study
  • 2015
  • In: Geriatrics & Gerontology International. - : Wiley. - 1444-1586 .- 1447-0594. ; 15:12, s. 1242-1248
  • Journal article (peer-reviewed)abstract
    • Aim: To investigate the associations between medication use and functional dependence in Chinese older people living in a rural community. Methods: The cross-sectional study included 1538 participants (age >= 60 years, 59.1% women) in the Confucius Hometown Aging Project in Shandong, China. In June 2010 to July 2011, data on demographics, lifestyle factors, health history, basic activities of daily living (ADL), instrumental ADL, and use of medications were collected through interviews and clinical examinations. Functional status was categorized into no dependence, dependence only in instrumental ADL and dependence in basic ADL. Data were analyzed with multinomial logistic models controlling for potential confounders. Results: Dependence in instrumental or basic ADL was significantly associated with use of antihypertensives and hypolipidemic agents, and basic ADL dependence was also associated with use of sedatives or tranquilizers and cardiac glycosides. An increased number of concurrently used medications was significantly associated with an increased likelihood of dependence in basic ADL (P for trend = 0.016). Compared with non-users of any medication, individuals who concurrently used three or more classes of medications had a multi-adjusted odds ratio of 2.91 (95% confidence interval 1.02-8.28) for dependence in basic ADL. Conclusions: Use of antihypertensives, hypolipidemic drugs, cardiac glycosides and sedatives or tranquilizers, especially use of multiple classes of medications, is correlated with functional dependence among older people in rural China.
  •  
34.
  • Liu, Yu, et al. (author)
  • Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus
  • 2023
  • In: Journal of Inflammation Research. - : Dove Medical Press. - 1178-7031. ; 16, s. 5367-5383
  • Journal article (peer-reviewed)abstract
    • Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.
  •  
35.
  • Lyu, Chuang, et al. (author)
  • Expression and regulation of FRMD6 in mouse DRG neurons and spinal cord after nerve injury
  • 2020
  • In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
  • Journal article (peer-reviewed)abstract
    • FRMD6, a member of the group of FERM-domain proteins, is involved both in communication between cells, interactions with extracellular matrix, cellular apoptotic and regenerative mechanisms. FRMD6 was first discovered in the rodent sciatic nerve, and in the present immunohistochemical study we investigated the distribution of FRMD6 in the dorsal root ganglia (DRGs), sciatic nerve and spinal cord following sciatic nerve injury. FRMD6-immunoreactivity was found in the cytoplasm, nucleus or both, and in a majority of DRG neurons. FRMD6-immunoreactivity co-existed with several well-known neuronal markers, including calcitonin gene-related peptide, isolectin B4 and neurofilament 200 in mouse DRGs. After peripheral nerve injury, the FRMD6 mRNA levels and the overall percentage of FRMD6-positive neuron profiles (NPs) were decreased in ipsilateral lumbar DRGs, the latter mainly affecting small size neurons with cytoplasmic localization. Conversely, the proportion of NPs with nuclear FRMD6-immunoreactivity was significantly increased. In the sciatic nerve, FRMD6-immunoreactivity was observed in non-neuronal cells and in axons, and accumulated proximally to a ligation of the nerve. In the spinal cord FRMD6-immunoreactivity was detected in neurons in both dorsal and ventral horns, and was upregulated in ipsilateral dorsal horn after peripheral nerve axotomy. Our results demonstrate that FRMD6 is strictly regulated by peripheral nerve injury at the spinal level.
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36.
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37.
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38.
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39.
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40.
  • Ramdas, S., et al. (author)
  • A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
  • 2022
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
  • Journal article (peer-reviewed)abstract
    • A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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41.
  • Song, Aiqin, et al. (author)
  • Highly prevalent and poorly controlled cardiovascular risk factors among Chinese elderly people living in the rural community
  • 2014
  • In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 21:10, s. 1267-1274
  • Journal article (peer-reviewed)abstract
    • Background The epidemiological scenario of cardiovascular risk factors (CRFs) among elderly people in rural China is unclear. We seek to describe the distribution, burden and management of major CRFs among older Chinese people living in the rural community. Methods This cross-sectional study included 1538 participants in the Confucius Hometown Aging Project (2010-2011) of people 60 years of age (mean age 68.6 years; 59.1% women) who lived in a rural community nearby Qufu, Shandong, China. Data were collected through a face-to-face interview, a clinical examination and laboratory tests. We carried out descriptive analysis on the prevalence and management of major CRFs. Results The overall prevalence of current smoking, physical inactivity, hypertension, diabetes, high cholesterol and obesity were 13.8%, 83.7%, 76.0%, 26.6%, 42.4% and 13.1%, respectively: 82.8% and 50.4% of participants had 2 and 3, respectively, of the six CRFs. Prevalence of alcohol consumption was 18.7%. Men were more likely to smoke and consume alcohol than women, whereas women were more likely to be obese and physically inactive than men (p<0.001). Prevalence of physical inactivity and hypertension increased with age, prevalence of alcohol intake and obesity decreased with age, and prevalence of smoking and diabetes was stable. Hypertension, diabetes and high cholesterol were treated in 60.6%, 68.1% and 41.1% of those with the disease, respectively, but only 11.3%, 13.7% and 31.7% achieved good control. Conclusions CRFs are highly prevalent and poorly controlled among elderly people in rural China, where men and women have different CRF profiles. Intervention programs targeting major CRFs may improve the health of older people in China.
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42.
  • Svensson, Thomas, et al. (author)
  • Association of Sleep Duration with All- And Major-Cause Mortality among Adults in Japan, China, Singapore, and Korea
  • 2021
  • In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:9
  • Journal article (peer-reviewed)abstract
    • Importance: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations. Objectives: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index. Design, Setting, and Participants: This cohort study of individual-level data from 9 cohorts in the Asia Cohort Consortium was performed from January 1, 1984, to December 31, 2002. The final population included participants from Japan, China, Singapore, and Korea. Mean (SD) follow-up time was 14.0 (5.0) years for men and 13.4 (5.3) years for women. Data analysis was performed from August 1, 2018, to May 31, 2021. Exposures: Self-reported sleep duration, with 7 hours as the reference category. Main Outcomes and Measures: Mortality, including deaths from all causes, cardiovascular disease, cancer, and other causes. Sex-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression with shared frailty models adjusted for age and the key self-reported covariates of marital status, body mass index, smoking status, alcohol consumption, physical activity, history of diabetes and hypertension, and menopausal status (for women). Results: For 322721 participants (mean [SD] age, 54.5 [9.2] years; 178542 [55.3%] female), 19419 deaths occurred among men (mean [SD] age of men, 53.6 [9.0] years) and 13768 deaths among women (mean [SD] age of women, 55.3 [9.2] years). A sleep duration of 7 hours was the nadir for associations with all-cause, cardiovascular disease, and other-cause mortality in both men and women, whereas 8 hours was the mode sleep duration among men and the second most common sleep duration among women. The association between sleep duration and all-cause mortality was J-shaped for both men and women. The greatest association for all-cause mortality was with sleep durations of 10 hours or longer for both men (hazard ratio [HR], 1.34; 95% CI, 1.26-1.44) and women (HR, 1.48; 95% CI, 1.36-1.61). Sex was a significant modifier of the association between sleep duration and mortality from cardiovascular disease (χ25= 13.47, P =.02), cancer (χ25= 16.04, P =.007), and other causes (χ25= 12.79, P =.03). Age was a significant modifier of the associations among men only (all-cause mortality: χ25= 41.49, P <.001; cancer: χ25= 27.94, P <.001; other-cause mortality: χ25= 24.51, P <.001). Conclusions and Relevance: The findings of this cohort study suggest that sleep duration is a behavioral risk factor for mortality in both men and women. Age was a modifier of the association between sleep duration in men but not in women. Sleep duration recommendations in these populations may need to be considered in the context of sex and age.
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43.
  • Takeuchi, Fumihiko, et al. (author)
  • Interethnic analyses of blood pressure loci in populations of East Asian and European descent
  • 2018
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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44.
  • Tu, Raoping, et al. (author)
  • The role of education in the association between self-rated health and levels of C-reactive protein : a cross-sectional study in rural areas of China
  • 2019
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 9:11
  • Journal article (peer-reviewed)abstract
    • Objectives This study aims to examine the association between self-rated health (SRH) and levels of C-reactive protein (CRP) among adults aged 45 to 101 years old in rural areas of China, and to explore the role of education in the association.Design Cross-sectional study.Setting The study population was derived from two databases in China: Nanping project (NP) and the China Health and Retirement Longitudinal Study (CHARLS).Participants There were 646 participants from a rural area of Nanping (NP) and 8555 rural participants from a national representative sample of China (CHARLS).Methods CRP was measured using a high sensitivity sandwich enzyme immunoassay in the NP and immunoturbidimetric assay in the GNARLS. SRH was assessed by SRH questionnaires and categorised into good and poor. Education was measured by the maximum years of schooling and dichotomised into illiterate and literate. Multivariate linear regression models were used to study the associations.Results Compared to people with good SRH, those with poor SRH had higher levels of CRP in NP beta=0.16, 95% CI -0.02 to 0.34) and in CHARLS (beta=0.07, 95% CI 0.02 to 0.11) after adjusting for potential confounders. Similar findings were observed in the pooled population (beta=0.08, 95% CI 0.03 to 0.12), especially in men (beta=0.13, 95% CI 0.06 to 0.20) and in literate people (beta=0.12, 95% CI 0.06 to 0.18).Conclusion Poor SRH may be a predicator of elevated levels of CRP among middle-aged and older people in rural areas, especially in men and literate people.
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45.
  • Ul Hassan, Imtiaz, et al. (author)
  • Genome-wide identification and spatiotemporal expression profiling of zinc finger SWIM domain-containing protein family genes
  • 2023
  • In: ZOOLOGICAL RESEARCH. - : Zoological Research. - 2095-8137. ; 44:3
  • Journal article (peer-reviewed)abstract
    • The biological function of the novel zinc-finger SWIM domain-containing protein family (ZSWIM) during embryonic development remains elusive. Here, we conducted a genome-wide analysis to explore the evolutionary processes of the ZSWIM gene family members in mice, Xenopus tropicalis, zebrafish, and humans. We identified nine putative ZSWIM genes in the human and mouse genome, eight in the Xenopus genome, and five in the zebrafish genome. Based on multiple sequence alignment, three members, ZSWIM5, ZSWIM6, and ZSWIM8, demonstrated the highest homology across all four species. Using available RNA sequencing (RNA-seq) data, ZSWIM genes were found to be widely expressed across different tissues, with distinct tissue-specific properties. To identify the functions of the ZSWIM protein family during embryogenesis, we examined temporal and spatial expression patterns of zswim family genes in Xenopus embryos. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that each member had a distinct expression profile. Whole-mount in situ hybridization showed that both zswim1 and zswim3 were maternally expressed genes; zswim5 and zswim6 were expressed throughout embryogenesis and displayed dynamic expression in the brain, eyes, somite, and bronchial arch at the late tailbud stages; zswim7 was detected in the eye area; zswim8 showed a dynamic expression pattern during the tailbud stages, with expression detected in the brain, eyes, and somite; zswim9 was faintly expressed throughout embryonic development. This study provides a foundation for future research to delineate the functions of ZSWIM gene members.
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46.
  • Wang, Fang, et al. (author)
  • Emerging contaminants: A One Health perspective
  • 2024
  • In: Innovation. - 2666-6758. ; 5
  • Research review (peer-reviewed)abstract
    • Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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47.
  • Wang, Hui, et al. (author)
  • A red- emissive mitochondrial probe for imaging of the viscosity in living cells
  • 2019
  • In: New Journal of Chemistry. - : ROYAL SOC CHEMISTRY. - 1144-0546 .- 1369-9261. ; 43:22, s. 8811-8815
  • Journal article (peer-reviewed)abstract
    • A novel water- soluble fluorescent probe L based on indole salts has been designed, synthesized and fully characterized. The systematic investigations demonstrated that probe L shows red emission and the fluorescence intensity is linear with the viscosity of the medium. Probe L is able to selectively accumulate in mitochondria within 1 min without any additional reagents for membrane permeabilization. It has been used to distinguish the viscosity differences between mitochondria in normal and nystatin- treated HeLa cells. In addition, due to the good photostability, probe L can be used to monitor the dynamics of mitochondria. These results support that probe L might provide a promising approach for the fluorescence detection of mitochondrial viscosity in living biological systems.
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48.
  • Wang, Hui, et al. (author)
  • Endoplasmic reticulum-targeted fluorogenic probe based on pyrimidine derivative for visualizing exogenous/endogenous H2S in living cells
  • 2020
  • In: Dyes and pigments. - : ELSEVIER SCI LTD. - 0143-7208 .- 1873-3743. ; 179
  • Journal article (peer-reviewed)abstract
    • Developing new probes for visualizing H2S in the endoplasmic reticulum (ER) is of great significance in physiological and pathological fields in that the probe can antagonise ER stress. Herein, we try to explore efficient reporting fluorophores based on three pyrimidine derivatives (L1, L2 and L3), and eventually, a novel probe WH2S was fabricated by using emissive pyrimidine derivative (L1) as the reporting fluomphore. Upon the addition of H2S, the probe processed a thiolytic cleavage to regenerate L1, delivering a remarkable fluorescence enhancement. Probe WH2S presents a perfect selectivity, high sensitivity and low detection limit (3.81 mu M) towards H2S in the buffer media. Most importantly, fluorescence microscopy experiments demonstrate that WH2S can precisely accumulate in ER and detect exogenous/endogenous H2S at cellular level. These results imply that probe WH2S possesses great potentiality in tracking target H2S in complicated and changeable living systems.
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49.
  • Wang, Rui, et al. (author)
  • Prevalence and Patterns of Chronic Disease Pairs and Multimorbidity among Older Chinese Adults Living in a Rural Area
  • 2015
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
  • Journal article (peer-reviewed)abstract
    • Background The burden of chronic diseases in China is substantial now. Data on patterns of chronic diseases and multimorbidity among older adults, especially among those living in rural areas, are sparse. Objective We aim to investigate the prevalence and patterns of chronic disease pairs and multimorbidity in elderly people living in rural China. Methods This population-based study included 1480 adults aged 60 years and over (mean age 68.5 years, 59.4% women) living in a rural community. Data were derived from the Confucius Hometown Aging Project in Shandong, China (June 2010-July 2011). Chronic diseases were diagnosed through face-to-face interviews, clinical examinations, and laboratory tests. Patterns of chronic disease pairs and multimorbidity were explored using logistic regression and exploratory factor analyses. Results The prevalence of individual chronic diseases ranged from 3.0% for tumor to 76.4% for hypertension, and each disease was often accompanied with three or more other chronic diseases. The observed prevalence of pairs of chronic conditions exceeded the expected prevalence for several conditions, such as cardiovascular diseases and metabolic disorders, as well as pulmonary diseases and degenerative disorders. Chronic multimorbidity (>= 2 chronic diseases) affected more than 90% of subjects, and two patterns of chronic multimorbidity were identified: cardiopulmonary-mental-degenerative disorder pattern (overall prevalence, 58.2%), and cerebrovascular-metabolic disorder pattern (62.6%). Prevalence of the cardiopulmonary-mental-degenerative disorder pattern increased with age, and was higher in men than women; whereas prevalence of the cerebrovascular-metabolic disorder pattern was higher in women than in men but did not vary by age. Conclusion Chronic multimorbidity was highly prevalent among older Chinese adults living in rural areas, and there were specific patterns of the co-occurrence of chronic diseases. Effort is needed to identify possible preventative strategies based on the potential clustering of chronic diseases.
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50.
  • Yan, Zhongrui, et al. (author)
  • Metabolic Syndrome and Subclinical Carotid Atherosclerosis Among Chinese Elderly People Living in a Rural Community
  • 2014
  • In: Metabolic Syndrome and Related Disorders. - : Mary Ann Liebert Inc. - 1540-4196 .- 1557-8518. ; 12:5, s. 269-276
  • Journal article (peer-reviewed)abstract
    • Background: The relationship between the metabolic syndrome and subclinical atherosclerosis among elderly people remains controversial. We seek to investigate the associations of metabolic syndrome and its components with subclinical carotid atherosclerosis in older people living in rural China. Methods: This cross-sectional study included 911 participants (age >= 60 years, 59.4% women) of the community-based Confucius Hometown Aging Project in Shandong, China, who were free of clinical cardiovascular disease. In 2010-2011, data were collected through interviews, clinical examinations, and laboratory tests. Carotid intima media thickness (cIMT) and carotid artery plaque were assessed using ultrasonography. Metabolic syndrome was defined by four sets of criteria. Data were analyzed with multiple general linear and logistic regression models. Results: Carotid plaque was detected in 514 (56.4%) persons. Depending on the defining criteria, prevalence of metabolic syndrome ranged from 30.6% to 56.9%. Hypertension, elevated blood pressure (>= 130/85 mmHg), diabetes/prediabetes, and high fasting plasma glucose (>= 5.6 mmol/L) were significantly associated with an increased likelihood of carotid plaque, whereas an increased cIMT was associated with elevated blood pressure and hypertension (P < 0.05). Obesity, high triglycerides, and dyslipidemia were not associated with carotid artery plaque or cIMT. The significant association of metabolic syndrome with an increased likelihood of carotid plaque disappeared when elevated blood pressure and high plasma glucose were added to the models. Metabolic syndrome was not associated with cIMT. Conclusions: Metabolic syndrome is associated with subclinical carotid plaque among Chinese elderly people, driven primarily by elevated blood pressure and hyperglycemia. Older adults with metabolic syndrome, especially those with high blood pressure and hyperglycemia, may benefit from evaluation for subclinical atherosclerosis.
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