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1.
Chem Commun (Camb) ; 60(79): 11152-11155, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39291541

RESUMO

Zigzag-shaped [6]phenacene isomers with fused thiophene rings, fulmineno[2,1-b:10,9-b']dithiophene (FuDT-α) and fulmineno[1,2-b:9,10-b']dithiophene (FuDT-ß), were syntheized and their p-type organic semicondutor properties were studied. Small effective masses of holes were estimated from the crystal structures of both isomers, which was particularly demonstrated by the hole mobility of 10.5 cm2 V-1 s-1 for FuDT-α single crystals.

2.
Circ J ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39198193

RESUMO

BACKGROUND: Anemia, a common comorbidity in older patients with heart failure (HF) and atrial fibrillation (AF), is associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF. METHODS AND RESULTS: We prospectively evaluated data of 1,388 patients with AF from the Hokuriku-Plus AF Registry (1,010 men; mean [±SD] age 72.3±9.7 years) and recorded the incidence of death, HF, thromboembolism, and major bleeding. Of these patients, the 1,233 for whom hemoglobin levels were available at baseline and at the 1-year follow-up were further evaluated. Patients were categorized into 3 groups based on longitudinal changes in 1-year anemia status: Group 1, AF without anemia; Group 2, AF with improved anemia; and Group 3, AF with sustained or new-onset anemia. Over the 1-5 years of follow up, the incidences of death, HF, thromboembolism, and major bleeding were significantly higher among patients with than without anemia. In addition, the incidence of death or HF was significantly higher in Group 3 than in Groups 1 and 2. Multivariate analysis revealed no anemia or improvement in anemia in 1 year as an independent predictor for a favorable prognosis for cardiovascular death and HF. CONCLUSIONS: Recovery from anemia may be associated with a favorable clinical course of AF.

3.
Circ J ; 87(12): 1790-1797, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37866911

RESUMO

BACKGROUND: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan.Methods and Results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5-5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56-6.21), the CHA2DS2-VASc score (1.35, 1.18-1.54), and concomitant HCM (2.48, 1.16-4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72-4.43), older age (1.07, 1.05-1.10), lower body mass index (0.95, 0.91-0.99), a history of HF (2.49, 1.77-3.52), and lower left ventricular ejection fraction (0.98, 0.97-0.99) were significantly associated with the development of HF. CONCLUSIONS: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.


Assuntos
Fibrilação Atrial , Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Acidente Vascular Cerebral , Tromboembolia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Volume Sistólico , Tromboembolia/etiologia , Tromboembolia/complicações , Função Ventricular Esquerda , Feminino
4.
Europace ; 25(6)2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37386841

RESUMO

AIMS: Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP). METHODS AND RESULTS: We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C. CONCLUSION: These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.


Assuntos
Síndrome do QT Longo , Torsades de Pointes , Humanos , Torsades de Pointes/diagnóstico , Torsades de Pointes/genética , Simulação por Computador , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Mutação , Proteínas de Ligação a DNA , Canal de Potássio ERG1/genética
5.
J Mol Cell Cardiol ; 177: 50-61, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36898499

RESUMO

Genetic testing for inherited arrhythmias and discriminating pathogenic or benign variants from variants of unknown significance (VUS) is essential for gene-based medicine. KCNQ1 is a causative gene of type 1 long QT syndrome (LQTS), and approximately 30% of the variants found in type 1 LQTS are classified as VUS. We studied the role of zebrafish cardiac arrhythmia model in determining the clinical significance of KCNQ1 variants. We generated homozygous kcnq1 deletion zebrafish (kcnq1del/del) using the CRISPR/Cas9 and expressed human Kv7.1/MinK channels in kcnq1del/del embryos. We dissected the hearts from the thorax at 48 h post-fertilization and measured the transmembrane potential of the ventricle in the zebrafish heart. Action potential duration was calculated as the time interval between peak maximum upstroke velocity and 90% repolarization (APD90). The APD90 of kcnq1del/del embryos was 280 ± 47 ms, which was significantly shortened by injecting KCNQ1 wild-type (WT) cRNA and KCNE1 cRNA (168 ± 26 ms, P < 0.01 vs. kcnq1del/del). A study of two pathogenic variants (S277L and T587M) and one VUS (R451Q) associated with clinically definite LQTS showed that the APD90 of kcnq1del/del embryos with these mutant Kv7.1/MinK channels was significantly longer than that of Kv7.1 WT/MinK channels. Given the functional results of the zebrafish model, R451Q could be reevaluated physiologically from VUS to likely pathogenic. In conclusion, functional analysis using in vivo zebrafish cardiac arrhythmia model can be useful for determining the pathogenicity of loss-of-function variants in patients with LQTS.


Assuntos
Síndrome do QT Longo , Peixe-Zebra , Animais , Humanos , Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/genética , Mutação , RNA Complementar , Virulência , Peixe-Zebra/genética
7.
Circ J ; 87(7): 939-946, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-36464278

RESUMO

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Humanos , Masculino , Idoso , Feminino , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Volume Sistólico , Resultado do Tratamento , Insuficiência Cardíaca/terapia , Ablação por Cateter/efeitos adversos , Sistema de Registros
8.
Heart Vessels ; 38(3): 402-411, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36251049

RESUMO

Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0 years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 from the Hokuriku-Plus AF Registry. The primary outcome was incident WKF, defined as the %eGFR change from the baseline ≥ 30% during the follow-up period. We evaluated the association between baseline variables and incident WKF using univariate and multivariate Cox proportional hazard models. We also evaluated the non-linear association between the identified factors and incident WKF. During a median follow-up period of 3.0 years (interquartile range: 2.7-3.3), incident WKF was observed in 108 patients (32.6 per 1000 person-years). Compared to the patients without incident WKF, the patients with incident WKF were older and had a higher prevalence of heart failure (HF), diabetes mellitus (DM), and vascular disease at baseline. Those who experienced incident WKF also had higher diastolic blood pressure, lower hemoglobin, lower eGFR, higher B-type natriuretic peptide (BNP) and used warfarin more frequently. Upon multivariate analysis, age ≥ 75 years, HF, DM, and anemia were independently associated with incident WKF. Additionally, age and hemoglobin were linearly associated with the risk of incident WKF, whereas a J- or U-shaped association was observed for HbA1c and BNP. Age ≥ 75 years, HF, DM, and anemia were associated with the development of WKF in Japanese patients with NVAF. In patients with these risk factors, a careful monitoring of the kidney function and appropriate interventions may be important when possible.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Masculino , Humanos , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/complicações , Varfarina , Fatores de Risco , Rim , Sistema de Registros
9.
Circ Rep ; 4(7): 298-307, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35860347

RESUMO

Background: Few studies in Japan have reported on follow-up data regarding the clinical course and risk factors for adverse outcomes in elderly patients with non-valvular atrial fibrillation (NVAF), vs. younger patients, when considering the competing risk of death. Methods and Results: We prospectively studied 1,328 patients with NVAF (965 men; mean [±SD] age 72.4±9.7 years) from the Hokuriku-Plus AF Registry with a median follow-up of 5.0 years (interquartile range 3.5-5.3 years) and evaluated the incidence of thromboembolism or major bleeding in elderly (age ≥75 years; n=595) and non-elderly (age <75 years; n=733) patients. Analysis using the Gray method showed no significant difference in the incidence of thromboembolism; however, the incidence of major bleeding was significantly higher in the elderly than non-elderly group. The Fine-Gray model, after adjustment for age and sex in the elderly group, showed that age (hazard ratio [HR] 1.08; 95% confidence interval [CI] 1.02-1.13; P=0.004) and warfarin use (HR 1.87; 95% CI 1.12-3.14; P=0.02) were significantly associated with major bleeding. In the elderly group, those using warfarin had a higher incidence of thromboembolism and major bleeding than those using direct oral anticoagulants (DOACs). Conclusions: The efficacy and safety of DOACs were remarkable in elderly compared with non-elderly patients with NVAF considering the competing risk of death. DOACs may be a favorable choice in elderly patients with NVAF.

10.
J Atheroscler Thromb ; 29(5): 667-677, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34011801

RESUMO

AIM: This study aimed to elucidate the gene and lipid profiles of children clinically diagnosed with familial hypercholesterolemia (FH). METHODS: A total of 21 dyslipidemia-related Mendelian genes, including FH causative genes (LDLR, APOB, and PCSK9) and LDL-altering genes (APOE, LDLRAP1, and ABCG5/8), were sequenced in 33 Japanese children (mean age, 9.7±4.2 years) with FH from 29 families. RESULTS: Fifteen children (45.5%) with pathogenic variants in LDLR (eight different heterozygous variants) and one child (3.0%) with the PCSK9 variant were found. Among 17 patients without FH causative gene variants, 3 children had variants in LDL-altering genes, an APOE variant and two ABCG8 variants. The mean serum total cholesterol (280 vs 246 mg/dL), LDL-cholesterol (LDL-C, 217 vs 177 mg/dL), and non-HDL cholesterol (228 vs 188 mg/dL) levels were significantly higher in the pathogenic variant-positive group than in the variant-negative group. In the variant-positive group, 81.3% of patients had LDL-C levels ≥ 180 mg/dL but 35.3% in the variant-negative group. The mean LDL-C level was significantly lower in children with missense variants, especially with the p.Leu568Val variant, than in children with other variants in LDLR, whereas the LDL-altering variants had similar effects on the increase in serum LDL-C to LDLR p.Leu568Val. CONCLUSION: Approximately half of the children clinically diagnosed with FH had pathogenic variants in FH causative genes. The serum LDL-C levels tend to be high in FH children with pathogenic variations, and the levels are by the types of variants. Genetic analysis is useful; however, further study on FH without any variants is required.


Assuntos
Hiperlipoproteinemia Tipo II , Pró-Proteína Convertase 9 , Adolescente , Apolipoproteínas E/genética , Criança , Pré-Escolar , Colesterol , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Japão/epidemiologia , Fenótipo , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética
11.
Circ J ; 85(11): 2073-2078, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34011825

RESUMO

BACKGROUND: Recent studies suggest that cumulative exposure to low-density lipoprotein-cholesterol (LDL-C) leads to the development of atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated whether this link extends to individuals with familial hypercholesterolemia (FH), a relevant patient population.Methods and Results:We retrospectively investigated the health records of 1,050 patients with clinical FH diagnosis between April 1990 and March 2019. We used Cox proportional hazards models adjusted for established ASCVD risk factors to assess the association between cholesterol-year-score and major adverse cardiovascular events (MACEs), including death from any cause or hospitalization due to ASCVD events. Cholesterol-year-score was calculated as LDL-C max × [age at diagnosis/statin initiation] + LDL-C at inclusion × [age at inclusion - age at diagnosis/statin initiation]. The median follow-up period for MACE evaluation was 12.3 (interquartile range, 9.1-17.5) years, and 177 patients experienced MACEs during the observation period. Cholesterol-year-score was significantly associated with MACEs (hazard ratio, 1.35; 95% confidence interval, 1.07-1.53; P=0.0034, per 1,000 mg-year/dL), independent of other traditional risk factors including age and LDL-C, based on cross-sectional assessment. Cholesterol-year-score improved the discrimination ability of other traditional risk factors for ASCVD events (C-index, 0.901 vs. 0.889; P=0.00473). CONCLUSIONS: Cumulative LDL-C exposure was strongly associated with MACEs in Japanese patients with FH, warranting early diagnosis and treatment initiation in these patients.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Aterosclerose/tratamento farmacológico , Colesterol , LDL-Colesterol , Estudos Transversais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Pró-Proteína Convertase 9 , Estudos Retrospectivos
13.
J Clin Lipidol ; 15(2): 358-365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33461934

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: We aimed to evaluate the prognostic impact of cascade screening for FH. METHODS: We retrospectively investigated the health records of 1050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiac events (MACE). The median period of follow-up evaluating MACE was 12.3 years (interquartile ranges [IQR] = 9.1-17.5 years), and MACE included death associated with ASCVD, or acute coronary syndrome. RESULTS: During the observation period, 113 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P < 0.0001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.67; 95%CI = 0.44 to 0.90; P = 0.0044) when compared with the probands, even after adjusting for those known risk factors, including age, and prior ASCVD. CONCLUSIONS: The identification of patients with FH via cascade screening appeared to result in better prognosis.


Assuntos
Hiperlipoproteinemia Tipo II , Adolescente , Adulto , Humanos , Hipercolesterolemia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Circ J ; 85(6): 891-897, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33268660

RESUMO

BACKGROUND: This study is aimed to compare the efficacy of the 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria, which focuses on only 3 essential clinical manifestations, with that of Dutch Lipid Clinic Network (DLCN) FH criteria, which adopts a scoring system of multiple elements.Methods and Results:A total of 680 Japanese dyslipidemic participants (51% men) were enrolled between 2006 and 2018, all of whom had full evaluations of low-density lipoprotein (LDL) cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (LDLR,APOB, andPCSK9). Predictive values for the existence of FH mutations by both clinical criteria were evaluated. Overall, 173 FH patients were clinically diagnosed by using the 2017 JAS criteria and 100, 57, 156, and 367 subjects were also diagnosed as having definite, probable, possible, and unlikely FH by the DLCN FH criteria, respectively. The positive and negative likelihood ratio predicting the presence of FH mutations by using the 2017 JAS FH criteria were 19.8 and 0.143, respectively; whereas, using the DLCN criteria of definite, probable, and possible FH, the ratios were 29.2 and 0.489, 9.70 and 0.332, and 3.43 and 0.040, respectively. CONCLUSIONS: Among Japanese patients, the JAS 2017 FH criteria is considered superior to diagnose FH mutation-positive patients and simultaneously rule out FH mutation-negative patients compared with the DLCN FH criteria.


Assuntos
Aterosclerose , Hiperlipoproteinemia Tipo II , Aterosclerose/diagnóstico , Aterosclerose/genética , Feminino , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Japão , Lipídeos , Masculino , Mutação , Fenótipo , Receptores de LDL/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-32936022

RESUMO

Background - Mutation/variant-site specific risk stratification in long-QT syndrome type 1 (LQT1) has been well investigated, but it is still challenging to adapt current enormous genomic information to clinical aspects caused by each mutation/variant. We assessed a novel variant-specific risk stratification in LQT1 patients. Methods - We classified a pathogenicity of 141 KCNQ1 variants among 927 LQT1 patients (536 probands) based on the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines and evaluated whether the ACMG/AMP-based classification was associated with arrhythmic risk in LQT1 patients. Results - Among 141 KCNQ1 variants, 61 (43.3%), 55 (39.0%), and 25 (17.7%) variants were classified into pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS), respectively. Multivariable analysis showed that proband (HR = 2.53; 95%CI = 1.94-3.32; p <0.0001), longer QTc (≥500ms) (HR = 1.44; 95%CI = 1.13-1.83; p = 0.004), variants at membrane spanning (MS) (vs. those at N/C terminus) (HR = 1.42; 95%CI = 1.08-1.88; p = 0.01), C-loop (vs. N/C terminus) (HR = 1.52; 95%CI = 1.06-2.16; p = 0.02), and P variants [(vs. LP) (HR = 1.72; 95%CI = 1.32-2.26; p <0.0001), (vs. VUS) (HR = 1.81; 95%CI = 1.15-2.99; p = 0.009)] were significantly associated with syncopal events. The ACMG/AMP-based KCNQ1 evaluation was useful for risk stratification not only in family members but also in probands. A clinical score (0~4) based on proband, QTc (≥500ms), variant location (MS or C-loop) and P variant by ACMG/AMP guidelines allowed identification of patients more likely to have arrhythmic events. Conclusions - Comprehensive evaluation of clinical findings and pathogenicity of KCNQ1 variants based on the ACMG/AMP-based evaluation may stratify arrhythmic risk of congenital long-QT syndrome type 1.

16.
J Am Chem Soc ; 142(35): 14974-14984, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32812421

RESUMO

Toward the development of high-performance organic semiconductors (OSCs), carrier mobility is the most important requirement for next-generation OSC-based electronics. The strategy is that OSCs consisting of a highly extended π-electron core exhibit two-dimensional (2D) aggregated structures to offer effective charge transport. However, such OSCs, in general, show poor solubility in common organic solvents, resulting in limited solution processability. This is a critical trade-off between the development of OSCs with simultaneous high carrier mobility and suitable solubility. To address this issue, herein, five-membered ring-fused selenium-bridged V-shaped binaphthalene with decyl substituents (C10-DNS-VW) is developed and synthesized by an efficient method. C10-DNS-VW exhibits significantly high solubility for solution processes. Notably, C10-DNS-VW forms a one-dimensional π-stacked packing motif (1D motif) and a 2D herringbone (HB) packing motif (2D motif), depending on the crystal growth condition. On the other hand, the fabrication of thin films by means of both solution process and vacuum deposition techniques forms only the 2D HB motif. External stress tests such as heating and exposure to solvent vapor indicated that 1D and 2D motifs could be synergistically induced by the total balance of intermolecular interactions. Finally, the single-crystalline films of C10-DNS-VW by solution process exhibit carrier mobility up to 11 cm2 V-1 s-1 with suitable transistor stability under ambient conditions for more than two months, indicating that C10-DNS-VW is one of the most promising candidates for breaking the trade-off in the field of solution-processed technologies.

17.
Sci Adv ; 6(18): eaaz0632, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494668

RESUMO

Organic semiconductors (OSCs) are important active materials for the fabrication of next-generation organic-based electronics. However, the development of n-type OSCs lags behind that of p-type OSCs in terms of charge-carrier mobility and environmental stability. This is due to the absence of molecular designs that satisfy the requirements. The present study describes the design and synthesis of n-type OSCs based on challenging molecular features involving a π-electron core containing electronegative N atoms and substituents. The unique π-electron system simultaneously reinforces both electronic and structural interactions. The current n-type OSCs exhibit high electron mobilities with high reliability, atmospheric stability, and robustness against environmental and heat stresses and are superior to other existing n-type OSCs. This molecular design represents a rational strategy for the development of high-end organic-based electronics.

18.
J Interv Cardiol ; 2020: 1956015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410915

RESUMO

OBJECTIVES: We evaluated the effect of the different carrier systems on early vascular response through histological analysis and scanning electron microscopy using a porcine model. BACKGROUND: Although Synergy™ and Promus PREMIER™ share an identical stent material and drug elution (everolimus), they use different drug carrier systems: biodegradable abluminal coating polymer or durable conformal coating polymer, respectively. However, data regarding the impact of the different coating systems on vessel healing are currently limited. METHODS: Twelve Synergy™ and Promus PREMIER™ were implanted in 12 swine. Histopathological analysis of the stented segments was performed on the 2nd and 14th days after implantation. Morphometric analysis of the inflammation and intimal fibrin content was also performed. RESULTS: On the 2nd day, neointimal thickness, percentage of neointimal area, and inflammatory and intimal fibrin content scores were not significantly different between the two groups. On the 14th day, the inflammatory and intimal fibrin content scores were significantly lower in Synergy™ versus those observed in Promus PREMIER™. In Synergy™, smooth muscle cells were found and the neointimal layers were smooth. In contrast, inflammatory cells were observed surrounding the struts of Promus PREMIER™. CONCLUSIONS: These results demonstrate that termination of reactive inflammation is accelerated after abluminal coating stent versus implantation of conformal coating stent.


Assuntos
Vasos Coronários , Stents Farmacológicos , Inflamação/prevenção & controle , Neointima/imunologia , Stents/efeitos adversos , Enxerto Vascular/instrumentação , Implantes Absorvíveis , Animais , Materiais Revestidos Biocompatíveis/farmacologia , Vasos Coronários/imunologia , Vasos Coronários/cirurgia , Portadores de Fármacos/farmacologia , Everolimo/farmacologia , Inflamação/etiologia , Modelos Anatômicos , Polímeros/farmacologia , Suínos
19.
J Am Chem Soc ; 142(20): 9083-9096, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32293879

RESUMO

Significant progress has been made in both molecular design and fundamental scientific understanding of organic semiconductors (OSCs) in recent years. Suitable charge-carrier mobilities (µ) have been obtained by many high-performance OSCs (µ > 10 cm2 V-1 s-1), but drawbacks remain, including low solution processability and poor thermal durability. In addition, since aggregation of OSCs involves weak intermolecular interactions, the molecules are perpetually in thermal motion, even in the solid state, which disrupts charge-carrier transport. These issues limit potential applications of OSCs. The present work examines a molecular design for hole-transporting (p-type) OSCs based on the "bent-shaped" geometry with specific molecular orbital configurations, which aims to enhance effective intermolecular orbital overlaps, stabilize crystal phases, suppress detrimental molecular motions in the solid state, and improve solution processability. The results indicated that such OSCs have high µ and suitable solution processability, and are resistant to ambient and thermal conditions, making them suitable for practical applications.

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