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1.
Hum Mol Genet ; 32(4): 677-684, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36164742

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.


Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/genética , Doença de Crohn/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Loci Gênicos , Polimorfismo de Nucleotídeo Único/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Proteínas de Transporte/genética , Proteínas de Membrana/genética , Proteases Específicas de Ubiquitina/genética
2.
Hum Mol Genet ; 31(22): 3934-3944, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-35512355

RESUMO

Genome-wide association studies (GWAS) of Crohn's disease (CD) in European and leprosy in Chinese population have shown that CD and leprosy share genetic risk loci. As these shared loci were identified through cross-comparisons across different ethnic populations, we hypothesized that meta-analysis of GWAS on CD and leprosy in East Asian populations would increase power to identify additional shared loci. We performed a cross-disease meta-analysis of GWAS data from CD (1621 cases and 4419 controls) and leprosy (2901 cases 3801 controls) followed by replication in additional datasets comprising 738 CD cases and 488 controls and 842 leprosy cases and 925 controls. We identified one novel locus at 7p22.3, rs77992257 in intron 2 of ADAP1, shared between CD and leprosy with genome-wide significance (P = 3.80 × 10-11) and confirmed 10 previously established loci in both diseases: IL23R, IL18RAP, IL12B, RIPK2, TNFSF15, ZNF365-EGR2, CCDC88B, LACC1, IL27, NOD2. Phenotype variance explained by the polygenic risk scores derived from Chinese leprosy data explained up to 5.28% of variance of Korean CD, supporting similar genetic structures between the two diseases. Although CD and leprosy shared a substantial number of genetic susceptibility loci in East Asians, the majority of shared susceptibility loci showed allelic effects in the opposite direction. Investigation of the genetic correlation using cross-trait linkage disequilibrium score regression also showed a negative genetic correlation between CD and leprosy (rg [SE] = -0.40[0.13], P = 2.6 × 10-3). These observations implicate the possibility that CD might be caused by hyper-sensitive reactions toward pathogenic stimuli.


Assuntos
Doença de Crohn , Hanseníase , Humanos , Estudo de Associação Genômica Ampla , Doença de Crohn/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , Loci Gênicos , Hanseníase/genética , Estudos de Casos e Controles , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
3.
J Autoimmun ; 145: 103206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554656

RESUMO

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.


Assuntos
Doença de Crohn , Memória Imunológica , Células T de Memória , Células Th17 , Humanos , Doença de Crohn/imunologia , Doença de Crohn/genética , Doença de Crohn/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células T de Memória/imunologia , Células T de Memória/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Biomarcadores , Perfilação da Expressão Gênica , Adulto Jovem
4.
Ecotoxicol Environ Saf ; 272: 116014, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295737

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are known to be representative carcinogenic environmental pollutants with high toxicity. However, information on the potential ecological and environmental risks of PAH contamination in soil remains scarce. Thus, this study was evaluated the potential ecological risks of PAHs in soils of five Korean areas (Gunsan (GS), Gwangju, Yeongnam, Busan, and Gangwon) using organic carbon (OC)-normalized analysis, mean effect range-median quotient (M-ERM-Q), toxic equivalent quantity (TEQ) analysis, and risk quotient (RQ) derived by the species sensitivity distribution model. In this study, atmospheric particulate matter has a significant effect on soil pollution in GS through the presence of hopanes and the similar pattern of PAHs in soil and atmospheric PAHs. From analysis of source identification, combustion sources in soils of GS were important PAH sources. For PAHs in soils of GS, the OC-normalized analysis, M-ERM-Q, and TEQ analysis have 26.78 × 105 ng/g-OC, 0.218, and 49.72, respectively. Therefore, the potential ecological risk assessment results showed that GS had moderate-high ecological risk and moderate-high carcinogenic risk, whereas the other regions had low ecological risk and low-moderate carcinogenic risk. The risk level (M-ERM-Q) of PAH contamination in GS was similar to that in Changchun and Xiangxi Bay in China. The Port Harcourt City in Nigeria for PAH has the highest risk (M-ERM-Q = 4.02 and TEQ = 7923). Especially, compared to China (RQPhe =0.025 and 0.05), and Nigeria (0.059), phenanthrene showed the highest ecological risk in Korea (0.001-0.18). Korea should focus on controlling the release of PAHs originating from the PM in GS.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo , Material Particulado/análise , Monitoramento Ambiental/métodos , Medição de Risco , Poluentes do Solo/análise , Nigéria , Carcinógenos/análise , China
5.
J Am Chem Soc ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37933129

RESUMO

Catalytic cross-couplings of tertiary alkyl electrophiles with carbon nucleophiles offer a powerful platform for constructing quaternary carbon centers, which are prevalent in bioactive molecules. However, these reactions remain underdeveloped primarily because of steric challenges that impede efficient bond formation. Herein, we describe the copper-catalyzed synthesis of such centers through the C(sp3)-C(sp2) bond-forming reaction between tertiary alkyl halides and arene rings of aniline derivatives, enabled by the strategic implementation of bidentate bis(cyclopropenimine) ligands. The copper catalyst bound by two imino-nitrogen atoms of these ligands, which have never been employed in metal catalysis previously, is highly effective in rapidly activating tertiary halides to generate alkyl radicals, allowing them to react with aryl nucleophiles under mild conditions with remarkably short reaction times (1-2 h). Various tertiary halides bearing carbonyl functional groups can be coupled with secondary or primary anilines, furnishing a range of quaternary carbon centers in good yields. Several mechanistic observations support the generation of copper(II) species and alkyl radicals which as a result elucidate the steps in the proposed catalytic cycle.

6.
N Engl J Med ; 382(1): 9, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31738483

RESUMO

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Anticolesterolemiantes/efeitos adversos , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Análise de Intenção de Tratamento , Ataque Isquêmico Transitório/complicações , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue
7.
Int J Mol Sci ; 25(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203383

RESUMO

The fruit flesh of watermelons differs depending on the distinct carotenoid composition. Orange-colored flesh relates to the accumulation of ß-carotene, which is beneficial to human health. Canary-yellow-fleshed OTO-DAH and orange-ß-fleshed (orange-fleshed with high ß-carotene) NB-DAH near-isogenic lines (NILs) were used to determine the genetic mechanism attributed to orange watermelon flesh. For genetic mapping, an F2 population was developed by crossing the two NILs. The segregation ratio of flesh color in the F2 population indicated that the orange-ß flesh of the NB-DAH NIL was controlled by a single incompletely dominant gene. Through a comparative analysis of the whole-genome sequences of the parent lines and NILs, a major introgression region unique to the NB-DAH NIL was detected on Chr. 1; this was considered a candidate region for harboring genes that distinguish orange from canary-yellow and red flesh. Among the 13 genes involved in the carotenoid metabolic pathway in watermelons, only ClPSY1 (ClCG01G008470), which encodes phytoene synthase 1, was located within the introgression region. The genotyping of F2 plants using a cleaved amplified polymorphic sequence marker developed from a non-synonymous SNP in ClPSY1 revealed its relationship with orange-ß flesh. The insights gained in this study can be applied to marker-assisted breeding for this desirable trait.


Assuntos
Melhoramento Vegetal , beta Caroteno , Humanos , Carotenoides , Marcadores Genéticos , Mapeamento Cromossômico
8.
J Radiol Prot ; 43(2)2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-36996806

RESUMO

The objective of this study is to update the national and regional indoor radon concentrations in South Korea and assess indoor radon exposure. Based on the previously published survey results and the collected measurement data of surveys conducted since 2011, a total of 9271 indoor radon measurement data covering 17 administrative divisions are finally used for analysis. The annual effective dose from the indoor radon exposure is calculated using dose coefficients recommended by the International Commission on Radiological Protection. The population-weighted average indoor radon concentration was estimated to be a geometric mean of 46 Bq m-3(GSD = 1.2) with 3.9% of all samples showing values exceeding 300 Bq m-3. The regional average indoor radon concentration ranged from 34 to 73 Bq m-3. The radon concentrations in detached houses were relatively higher than those in public buildings and multi-family houses. The annual effective doses to the Korean population due to indoor radon exposure were estimated to be 2.18 mSv. The updated values in this study might better represent the national indoor radon exposure level in South Korea because they contain more samples and cover a wider range of geographical areas than previous studies.


Assuntos
Poluentes Radioativos do Ar , Poluição do Ar em Ambientes Fechados , Monitoramento de Radiação , Radônio , Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Radônio/análise , República da Coreia , Habitação
9.
Phys Rev Lett ; 129(1): 015701, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35841582

RESUMO

Triple bonding in the nitrogen molecule (N_{2}) is among the strongest chemical bonds with a dissociation enthalpy of 9.8 eV/molecule. Nitrogen is therefore an excellent test bed for theoretical and numerical methods aimed at understanding how bonding evolves under the influence of the extreme pressures and temperatures of the warm dense matter regime. Here, we report laser-driven shock experiments on fluid molecular nitrogen up to 800 GPa and 4.0 g/cm^{3}. Line-imaging velocimetry measurements and impedance matching method with a quartz reference yield shock equation of state data of initially precompressed nitrogen. Comparison with numerical simulations using path integral Monte Carlo and density functional theory molecular dynamics reveals clear signatures of chemical dissociation and the onset of L-shell ionization. Combining data along multiple shock Hugoniot curves starting from densities between 0.76 and 1.29 g/cm^{3}, our study documents how pressure and density affect these changes in chemical bonding and provides benchmarks for future theoretical developments in this regime, with applications for planetary interior modeling, high energy density science, and inertial confinement fusion research.

10.
Proc Natl Acad Sci U S A ; 116(18): 8679-8684, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30988187

RESUMO

Crystal growth is governed by an interplay between macroscopic driving force and microscopic interface kinetics at the crystal-liquid interface. Unlike the local equilibrium growth condition, the interplay becomes blurred under local nonequilibrium, which raises many questions about the nature of diverse crystal growth and morphological transitions. Here, we systematically control the growth condition from local equilibrium to local nonequilibrium by using an advanced dynamic diamond anvil cell (dDAC) and generate anomalously fast growth of ice VI phase with a morphological transition from three- to two-dimension (3D to 2D), which is called a shock crystal growth. Unlike expected, the shock growth occurs from the edges of 3D crystal along the (112) crystal plane rather than its corners, which implies that the fast compression yields effectively large overpressure at the crystal-liquid interface, manifesting the local nonequilibrium condition. Molecular dynamics (MD) simulation reproduces the faster growth of the (112) plane than other planes upon applying large overpressure. Moreover, the MD study reveals that the 2D shock crystal growth originates from the similarity of the interface structure between water and the (112) crystal plane under the large overpressure. This study provides insight into crystal growth under dynamic compressions, which makes a bridge for the unknown behaviors of crystal growth between under static and dynamic pressure conditions.

11.
Angew Chem Int Ed Engl ; 61(49): e202214269, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36202753

RESUMO

Zeolitic imidazolate frameworks (ZIFs) are promising for gas separation membrane, but their molecular cut-off differs from that expected from its intrinsic aperture structure because of their flexibility. Herein, we introduced graphene nanoribbons (GNRs) to rigidify the ZIF framework. Because the sp2 edge of the GNRs induces strong anchoring effects, the modified layer can be rigidified. Particularly, when the GNRs were embedded and distributed in the ZIF-8 layer, an intrinsic aperture size of 3.4 Šwas observed, resulting in high H2 /CO2 separation (H2 permeance: 5.2×10-6  mol/m2 Pa s, ideal selectivity: 142). The performance surpasses the upper bound of polycrystalline MOF membrane performance. In addition, the membrane can be applied to blue H2 production, as demonstrated with a simulated steam reformed gas containing H2 /CO2 /CH4 . The separation performance was retained in the presence of water. The fundamentals of the molecular transport through the rigid ZIF-8 framework were revealed using molecular dynamics simulations.

12.
Stroke ; 52(5): 1662-1672, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33794654

RESUMO

Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events. Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 3­4). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed. Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.00­1.56) for ASVD 1, 1.34 (95% CI, 1.02­1.76) for ASVD 2, and 1.93 (95% CI, 1.24­2.99) for ASVD 3­4. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.01­1.74), 1.47 (1.06­2.03), and 2.39 (1.47­3.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.05­1.54]) and all-cause death (1.45 [1.17­1.81]). Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.


Assuntos
Doença da Artéria Coronariana , Bases de Dados Factuais , Doença Arterial Periférica , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Arteriosclerose Intracraniana , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia
13.
J Am Chem Soc ; 143(1): 73-79, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356216

RESUMO

We report here a stereodivergent method for the Michael addition of aryl acetic acid esters to α,ß-unsaturated aldehydes catalyzed by a combination of a chiral pyrrolidine and a chiral Lewis base. This reaction proceeds through a synergistic catalytic cycle which consists of one cycle leading to a chiral iminium electrophile and a second cycle generating a nucleophilic chiral enolate for the construction of a carbon-carbon bond. By varying the combinations of catalyst enantiomers, all four stereoisomers of the products with two vicinal stereocenters are accessible with high enantio- and diastereoselectivity. The products of the Michael addition, 1,5-aldehyde esters, can be readily transformed into a variety of other valuable enantioenriched structures, including those bearing three contiguous stereocenters in an acyclic system, thus providing an efficient route to an array of structural and stereochemical diversity.

14.
Cerebrovasc Dis ; 50(3): 288-295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33588410

RESUMO

BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.


Assuntos
Técnicas de Apoio para a Decisão , Avaliação da Deficiência , Serviços Médicos de Emergência , AVC Isquêmico/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Progressão da Doença , Feminino , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/fisiopatologia , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
15.
Stroke ; 51(3): 931-937, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31856691

RESUMO

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.


Assuntos
Aspirina/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Cilostazol/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Entropy (Basel) ; 22(9)2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-33286761

RESUMO

In this study, the problem of dynamic channel access in distributed underwater acoustic sensor networks (UASNs) is considered. First, we formulate the dynamic channel access problem in UASNs as a multi-agent Markov decision process, wherein each underwater sensor is considered an agent whose objective is to maximize the total network throughput without coordinating with or exchanging messages among different underwater sensors. We then propose a distributed deep Q-learning-based algorithm that enables each underwater sensor to learn not only the behaviors (i.e., actions) of other sensors, but also the physical features (e.g., channel error probability) of its available acoustic channels, in order to maximize the network throughput. We conduct extensive numerical evaluations and verify that the performance of the proposed algorithm is similar to or even better than the performance of baseline algorithms, even when implemented in a distributed manner.

17.
Infect Immun ; 87(1)2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30396896

RESUMO

Sialyllactose (SL) is a representative human milk oligosaccharide (HMO) of human breast milk. The roles of SL in infant brain development and immunity have been reported in previous studies. In this study, we identified the impact of SL on innate immunity. Our results showed that the administration of SL had significant efficacy on bacterial clearance in Pseudomonas aeruginosa K-infected mice. We also examined the role of SL in the human THP-1 macrophage-like cell line. SL effectively promoted receptor-mediated endocytosis and phagocytosis. Furthermore, SL accelerated the recruitment of Rac1 to the cell membrane, leading to the generation of reactive oxygen species for the elimination of phagocytosed bacteria. Our findings provide a new perspective on the role of SL in breast milk and suggest its application as a therapeutic agent to treat bacterial and viral infections.


Assuntos
Fatores Imunológicos/administração & dosagem , Lactose/análogos & derivados , Fagocitose/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Animais , Modelos Animais de Doenças , Humanos , Fatores Imunológicos/farmacologia , Lactose/administração & dosagem , Lactose/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Modelos Biológicos , Células THP-1 , Resultado do Tratamento
18.
Theor Appl Genet ; 132(2): 473-488, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30446794

RESUMO

KEY MESSAGE: A non-synonymous SNP of CC-NBS-LRR was firstly mapped to confer resistance to anthracnose in watermelon. Newly proposed LRR domain harboring the SNP is evolutionary conserved in the Cucurbitaceae and Fabaceae. Anthracnose disease caused by Colletotrichum devastates many plants. Despite the importance of the disease, the mechanisms of resistance against it are poorly understood. Here, we identified a non-synonymous single-nucleotide polymorphism (SNP) located in a leucine-rich repeat domain as a marker for resistance to anthracnose race 1 in watermelon, using a combination of genetic analyses. We validated this SNP in segregating populations and 59 watermelon accessions using high-resolution melting assays and Sanger sequencing. We demonstrated that the resulting arginine-to-lysine substitution is particularly conserved among the Cucurbitaceae and Fabaceae. We identified a conserved motif, IxxLPxSxxxLYNLQTLxL, found in 1007 orthologues/paralogues from 89 plant species, and discovered that residue 18 of this motif could determine resistance to disease caused by external invaders. This study provides a step forward in understanding anthracnose resistance in watermelon, as well as functional and evolutionary insight into leucine-rich repeat proteins.


Assuntos
Citrullus/genética , Resistência à Doença/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas/genética , Mapeamento Cromossômico , Citrullus/microbiologia , Colletotrichum/patogenicidade , Sequência Conservada , Genótipo , Proteínas de Repetições Ricas em Leucina , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único
19.
J Nanosci Nanotechnol ; 18(7): 5026-5032, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442689

RESUMO

Silicon (Si) is one of the most attractive anode materials for lithium secondary batteries because of its large theoretical capacity, high safety, low cost and environmental benignity. However, Si-based anode material needs to overcome the structural change of the solid-electrolyte interphase due to the large volume change during cycling. To resolve these problems of composites by exploiting the superior conductivity, large specific surface area and flexibility of graphene, we have synthesized reduced graphene oxide (rGO)/Si composite electrode via a simple dip-coating method. Nickel foam is used as a current collector and template for the electrode fabrication. At 0.03 wt%, Si concentration, the rGO/Si composite anode presented the excellent cycle performance with large reversible capacity (778 mAh g-1 after 100 cycles). The characteristics of the rGO/Si composites were analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Raman and X-ray photoelectron spectroscopy (XPS). The improved anode performance of the rGO/Si composite anode is ascribed to the rGO serving as a buffer layer, thereby preventing the volume expansion of Si nanoparticles, and provide facile electron pathways.

20.
Regul Toxicol Pharmacol ; 99: 238-243, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30268829

RESUMO

Eriobotrya japonica leaf is included in the Chinese Pharmacopoeia, and is widely used as a medicinal material in traditional medicine. The present study investigated the potential genotoxic effects of E. japonica leaf extract (EJE) using three standard battery systems. Genotoxicity tests were conducted following the test guidelines of the Organisation for Economic Cooperation and Development (OECD) and Ministry of Food and Drug Safety (MFDS), with application of Good Laboratory Practice. The bacterial reverse mutation test was conducted using the pre-incubation method in the presence or absence of the metabolic activation system (S9 mixture). The in vitro chromosome aberration test was performed using cultured Chinese hamster lung cell line in the presence or absence of the S9 mixture. The in vivo micronucleus test was performed using ICR mice. The bacterial reverse mutation test with Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2uvrA showed that EJE did not induce gene mutations at any dose level in all the strains tested. EJE also did not show any chromosomal aberrations in the in vitro chromosomal aberration test and in the in vivo micronucleus test. These results showed that EJE did not induce mutagenicity or clastogenicity in either in vitro or in vivo systems.


Assuntos
Eriobotrya/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/toxicidade , Animais , Linhagem Celular , Aberrações Cromossômicas/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes para Micronúcleos/métodos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Mutação/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos
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