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1.
J Am Chem Soc ; 145(30): 16324-16329, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37487017

RESUMO

The torsion angle between donor and acceptor segments of a thermally activated delayed fluorescence (TADF) molecule is one of the most critical factors in determining the performance of TADF-based organic light-emitting diodes (OLEDs) because the torsion angle affects not only the energy gap between the singlet and triplet but also the oscillator strength and spin-orbit coupling. However, the torsion angle is difficult to analyze, because organic molecules are in an amorphous state in OLEDs. Here, we determined the torsion angle of a highly efficient TADF emitter, DACT-II, in an amorphous state by dynamic nuclear polarization enhanced solid-state NMR measurements. From the experimentally obtained chemical shift principal values of 15N on carbazole, we determined the average torsion angle to be 52°. Such quantification of the torsion angles in TADF molecules in amorphous solids will provide deep insight into the TADF mechanism in amorphous OLEDs.

2.
Sci Rep ; 13(1): 11109, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37429886

RESUMO

Organic light-emitting diodes (OLEDs) using thermally activated delayed fluorescence (TADF) materials have advantages over OLEDs using conventional fluorescent materials or high-cost phosphorescent materials, including higher efficiency and lower cost. To attain further high device performance, clarifying internal charge states in OLEDs at a microscopic viewpoint is crucial; however, only a few such studies have been performed. Here, we report a microscopic investigation into internal charge states in OLEDs with a TADF material by electron spin resonance (ESR) at a molecular level. We observed operando ESR signals of the OLEDs and identified their origins due to a hole-transport material PEDOT:PSS, gap states at an electron-injection layer, and a host material CBP in the light-emitting layer by performing density functional theory calculation and studying thin films used in the OLEDs. The ESR intensity varied with increasing applied bias before and after the light emission. We find leakage electrons in the OLED at a molecular level, which is suppressed by a further electron-blocking layer MoO3 between the PEDOT:PSS and light-emitting layer, resulting in the enhancement of luminance with a low-voltage drive. Such microscopic information and applying our method to other OLEDs will further improve the OLED performance from the microscopic viewpoint.

3.
Org Lett ; 25(6): 998-1002, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36744816

RESUMO

Here, we explored the possibility of using cycloparaphenylenes (CPP) within a donor-acceptor TADF emitter design. 4PXZPh-[10]CPP contains four electron-donating moieties connected to a [10]CPP. In the 15 wt % doped in CzSi film, 4PXZPh-[10]CPP showed sky-blue emission with λPL = 475 nm, ΦPL = 29%, and triexponential emission decays with τPL of 4.4, 46.3, and 907.8 ns. Solution-processed OLEDs using 4PXZPh-[10]CPP exhibited sky-blue emission with an λEL of 465 nm and an EQEmax of 1.0%.

4.
ACS Omega ; 7(19): 16740-16745, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35601324

RESUMO

The members of the imidazole family have been widely used for electron transporting, host, conventional fluorescent, and phosphorescent materials. Although the imidazole core also has great potential as an acceptor segment of deep-blue thermally activated delayed fluorescence (TADF) owing to its high triplet energy, the emission color of imidazole-based TADF organic light-emitting diodes (OLEDs) has so far been limited to blue to green. In this work, four acridan-imidazole systems are theoretically designed aiming for deep- or pure-blue emitters. All four emitters exhibit deep-blue to blue emission owing to the high energy levels of the lowest excited singlet states, exhibiting y coordinates of Commission Internationale de l'Eclairage coordinates between 0.06 and 0.26. The molecule composed of a trifluoromethyl-substituted benzimidazole acceptor in combination with a tetramethyl-9,10-dihydroacridine donor (named MAc-FBI) achieves a high maximum external quantum efficiency (EQEMAX) of 13.7% in its application to vacuum-processed OLEDs. The emitter has high solubility even in ecofriendly nonhalogenated solvents, which motivates us to fabricate solution-processed MAc-FBI-based OLEDs, resulting in an even higher EQEMAX of 16.1%.

5.
Adv Sci (Weinh) ; 9(12): e2106018, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35224891

RESUMO

Thermally activated delayed fluorophores (TADF) with donor-acceptor (D-A) structures always face strong conjugation between donor and acceptor segments, rendering delocalized new molecular orbitals that go against blue emission. Developing TADF emitters with blue colors, high efficiencies, and long lifetimes simultaneously is therefore challenging. Here, a D-void-A structure with D and A moieties connected at the void-position where the frontier orbital from donor and acceptor cannot be distributed, resulting in nonoverlap of the orbitals is proposed. A proof-of-the-concept TADF emitter with 3,6-diphenyl-9H-carbazole (D) connected at the 3'3-positions of 9H-xanthen-9-one (A), the void carbon-atom with no distribution of the highest occupied molecular orbital (HOMO) of A-segment, realizes more efficient and blue-shifted emission compared with the contrast D-A isomers. The deeper HOMO-2 of A is found to participate into conjugation rather than HOMO, providing a wider-energy-gap. The corresponding blue device exhibits a y color coordinate (CIEy ) of 0.252 and a maximum external quantum efficiency of 27.5%. The stability of this compound is further evaluated as a sensitizer for a multiple resonance fluorophore, realizing a long lifetime of ≈650 h at an initial luminance of 100 cd m-2 with a CIEy of 0.195 and a narrowband emission with a full-width-at-half-maxima of 21 nm.

6.
Beilstein J Org Chem ; 17: 2894-2905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956408

RESUMO

In this work we showcase the emitter DICzTRZ in which we employed a twin-emitter design of our previously reported material, ICzTRZ. This new system presented a red-shifted emission at 488 nm compared to that of ICzTRZ at 475 nm and showed a comparable photoluminescence quantum yield of 57.1% in a 20 wt % CzSi film versus 63.3% for ICzTRZ. The emitter was then incorporated within a solution-processed organic light-emitting diode that showed a maximum external quantum efficiency of 8.4%, with Commission Internationale de l'Éclairage coordinate of (0.22, 0.47), at 1 mA cm-2.

7.
J Am Chem Soc ; 143(42): 17388-17394, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34647732

RESUMO

The conversion of a high-energy photon into two excitons using singlet fission (SF) has stimulated a variety of studies in fields from fundamental physics to device applications. However, efficient SF has only been achieved in limited systems, such as solid crystals and covalent dimers. Here, we established a novel system by assembling 4-(6,13-bis(2-(triisopropylsilyl)ethynyl)pentacen-2-yl)benzoic acid (Pc) chromophores on nanosized CdTe quantum dots (QDs). A near-unity SF (198 ± 5.7%) initiated by interfacial resonant energy transfer from CdTe to surface Pc was obtained. The unique arrangement of Pc determined by the surface atomic configuration of QDs is the key factor realizing unity SF. The triplet-triplet annihilation was remarkably suppressed due to the rapid dissociation of triplet pairs, leading to long-lived free triplets. In addition, the low light-harvesting ability of Pc in the visible region was promoted by the efficient energy transfer (99 ± 5.8%) from the QDs to Pc. The synergistically enhanced light-harvesting ability, high triplet yield, and long-lived triplet lifetime of the SF system on nanointerfaces could pave the way for an unmatched advantage of SF.

8.
J Org Chem ; 86(17): 11531-11544, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34323488

RESUMO

Three multichromophore thermally activated delayed fluorescence (TADF) molecules, p-di2CzPN, m-di2CzPN, and 1,3,5-tri2CzPN, were synthesized and characterized. These molecules were designed by connecting the TADF moiety 4,5-di(9H-carbazol-9-yl)phthalonitrile (2CzPN) to different positions of a central benzene ring scaffold. Three highly soluble emitters all exhibited near-quantitative photoluminescence quantum yields (ΦPL) in toluene. High ΦPLs were also achieved in doped films, 59 and 70% for p-di2CzPN and m-di2CzPN in 10 wt % DPEPO doped film, respectively, and 54% for 1,3,5-tri2CzPN in 20 wt % doped CBP films. The rate constant of reverse intersystem crossing (kRISC) for p-di2CzPN and m-di2CzPN in DPEPO films reached 1.1 × 105 and 0.7 × 105 s-1, respectively, and kRISC for 1,3,5-tri2CzPN in the CBP film reached 1.7 × 105 s-1. A solution-processed organic light-emitting diode based on 1,3,5-tri2CzPN exhibited a sky-blue emission with CIE coordinates of (0.22, 0.44) and achieved a maximum external quantum efficiency of 7.1%.

9.
Sci Rep ; 11(1): 6278, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737552

RESUMO

We utilized nanoporous mayenite (12CaO·7Al2O3), a cost-effective material, in the hydride state (H-) to explore the possibility of its use for hydrogen storage and transportation. Hydrogen desorption occurs by a simple reaction of mayenite with water, and the nanocage structure transforms into a calcium aluminate hydrate. This reaction enables easy desorption of H- ions trapped in the structure, which could allow the use of this material in future portable applications. Additionally, this material is 100% recyclable because the cage structure can be recovered by heat treatment after hydrogen desorption. The presence of hydrogen molecules as H- ions was confirmed by 1H-NMR, gas chromatography, and neutron diffraction analyses. We confirmed the hydrogen state stability inside the mayenite cage by the first-principles calculations to understand the adsorption mechanism and storage capacity and to provide a key for the use of mayenite as a portable hydrogen storage material. Further, we succeeded in introducing H- directly from OH- by a simple process compared with previous studies that used long treatment durations and required careful control of humidity and oxygen gas to form O2 species before the introduction of H-.

10.
Mol Psychiatry ; 26(9): 4958-4967, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32439845

RESUMO

Alterations in the cortical dopamine system and microglial activation have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), one of neurodevelopmental disorders that can be conventionally treated with a dopamine enhancer (methylphenidate) albeit unsatisfactorily. Here, we investigated the contributions of the dopamine D1 receptor (D1R) and activated microglia and their interactions to the clinical severities in ADHD individuals using positron emission tomography (PET). Twenty-four psychotropic-naïve ADHD individuals and 24 age- and sex-matched typically developing (TD) subjects underwent PET measurements with [11C]SCH23390 for the D1R and [11C](R)PK11195 for activated microglia as well as assessments of clinical symptoms and cognitive functions. The ADHD individuals showed decreased D1R in the anterior cingulate cortex (ACC) and increased activated microglia in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared with the TD subjects. The decreased D1R in the ACC was associated with severe hyperactivity in the participants with ADHD. Microglial activation in the DLPFC were associated with deficits in processing speed and attentional ability, and that in the OFC was correlated with lower processing speed in the ADHD individuals. Furthermore, positive correlations between the D1R and activated microglia in both the DLPFC and the OFC were found to be significantly specific to the ADHD group and not to the TD group. The current findings suggest that microglial activation and the D1R reduction as well as their aberrant interactions underpin the neurophysiological mechanism of ADHD and indicate these biomolecular changes as a novel therapeutic target.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Córtex Pré-Frontal Dorsolateral , Humanos , Imageamento por Ressonância Magnética , Microglia , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal , Receptores de Dopamina D1
11.
Eat Behav ; 40: 101449, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33246836

RESUMO

Previous research has suggested that emotion regulation strategies (ERSs) are associated with abnormal eating behaviors and attitudes (AEBs). Available data have demonstrated that frequent rumination, a major maladaptive ERS, is associated with elevated AEBs, whereas adaptive ERSs, such as problem-solving and cognitive reappraisal, showed negative associations with AEBs. Most previous studies examined the association of a single ERS with AEBs. Therefore, any significant associations between an individual ERS and AEB reported in previous research might stem from spurious correlations. The current cross-sectional study sought to examine simultaneous associations of four ERSs (rumination, problem-solving, distraction, and cognitive reappraisal) with two categories of ED symptoms (i.e., drive for thinness and bulimic symptoms) in early adolescents in Japan (ages 10-15, N = 5301). Participants self-reported their use of the different ERSs and the ED symptoms. We found certain ERSs were uniquely associated with levels of drive for thinness and bulimic symptoms even after controlling for body mass index, depression, and socioeconomic status. Particularly, frequent rumination in both boys and girls was associated with a severe drive for thinness and bulimic symptoms. Regarding adaptive strategies, frequent uses of problem-solving was associated with decreased bulimic symptoms only in girls, with the effect size being small. In addition, contrary to our expectation, greater use of distraction was associated with elevated AEBs, except the association with drive for thinness in boys. Although this study extended findings of previous research, prospective studies are required to clarify the causal relationship between ERSs and eating pathology.


Assuntos
Regulação Emocional , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Atitude , Criança , Estudos Transversais , Emoções , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Feminino , Humanos , Japão , Masculino , Estudos Prospectivos
12.
J Am Chem Soc ; 142(21): 9752-9762, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32352795

RESUMO

Visible-light-driven hydrogen (H2) production from water is a promising strategy to convert and store solar energy as chemical energy. Covalent organic frameworks (COFs) are front runners among different classes of organic photocatalysts. The photocatalytic activity of COFs depends on numerous factors such as the electronic band gap, crystallinity, surface area, exciton migration, stability of transient species, charge separation and transport, etc. However, it is challenging to fine tune all of these factors simultaneously to enhance the photocatalytic activity. Hence, in this report, an effort has been made to understand the interplay of these factors and identify the key factors for efficient photocatalytic H2 production through a structure-property-activity relationship. Careful molecular engineering allowed us to optimize all of the above plausible factors impacting the overall catalytic activities of a series of isoreticular COFs. The present study determines three prime factors: light absorption, charge carrier generation, and its transport, which influence the photocatalytic H2 production of COFs to a much greater extent than the other factors.

13.
Autism Res ; 13(5): 741-750, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32058662

RESUMO

A growing body of evidence has indicated that individuals with autism spectrum disorder (ASD) exhibit abnormal reactions to sensory stimuli and impaired face processing. Although behavioral studies have reported that individual differences in sensory processing patterns are correlated with performance in face processing tasks, the neural substrates underlying the association between sensory processing patterns and face processing remain unknown. Using functional magnetic resonance imaging, the present study examined the relationships between sensory processing patterns assessed with the Adolescent/Adult Sensory Profile (AASP) and brain activity during a one-back task with two types of stimuli (face or house pictures). We enrolled 18 Japanese adults with ASD and 19 age- and IQ-matched controls. Sensation Avoiding scores, which were assessed using the AASP, were positively correlated with right fusiform activity during the presentation of pictures of faces in the ASD group, but not in the control group. This suggests that abnormal sensory processing patterns in ASD are associated with abnormal face-related brain activity, possibly resulting in impaired face processing. Autism Res 2020, 13: 741-750. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Sensory abnormalities are one of the most common symptoms in people with autism spectrum disorder (ASD). This study shows that individuals with ASD who react abnormally to sensory stimuli also exhibit atypical brain activity when recognizing faces. Abnormal sensory processing may partly explain the difficulty that people diagnosed with ASD have in identifying others' faces.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Reconhecimento Facial/fisiologia , Lobo Temporal/fisiopatologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Japão , Imageamento por Ressonância Magnética/métodos , Masculino , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia
14.
Neuroimage Clin ; 23: 101928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31491815

RESUMO

The serotonin system has been implicated in the pathophysiology of anorexia nervosa (AN). A recent report proposed that body image distortion (BID), a core symptom of AN, may relate to abnormalities of the serotonin system, especially the serotonin transporter (5HTT). Positron emission tomography (PET) studies of underweight patients with active AN reported alterations in serotonin receptors, but not 5HTT. Here, we aimed to disclose the clinicopathophysiology of AN by focusing on 5HTT and cognitive functions, including BID, in groups with active AN. Twenty-two underweight female patients with AN (12 restricting-type AN (ANR); 10 binge-eating/purging-type AN (ANBP)) and 20 age-matched healthy female subjects underwent PET with a 5HTT radioligand [11C]DASB. The binding potential (BPND) of [11C]DASB was estimated semiquantitatively, and clinical data from Raven's colored progressive matrices for general intelligence, the Stroop test for focused attention, the Iowa gambling task for decision making and a dot-probe task designed for BID were compared with the levels of BPND in different groups. [11C]DASB BPND was significantly decreased in the medial parietal cortex in patients with AN and in the dorsal raphe in patients with ANR compared with healthy subjects (p < .05 corrected). Patients with ANR showed a significantly negative correlation between [11C]DASB BPND in the dorsal raphe and performance on the dot-probe task (p < .05 corrected). While reduced 5HTT in the medial parietal cortex (the somatosensory association area) is pathophysiologically important in AN in general, additional 5HTT reduction in the dorsal raphe as seen in ANR is implicated for the clinicopathophysiological relevance.


Assuntos
Anorexia Nervosa/metabolismo , Transtornos Dismórficos Corporais/metabolismo , Disfunção Cognitiva/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adolescente , Adulto , Compostos de Anilina/farmacocinética , Anorexia Nervosa/complicações , Anorexia Nervosa/diagnóstico por imagem , Anorexia Nervosa/fisiopatologia , Transtornos Dismórficos Corporais/diagnóstico por imagem , Transtornos Dismórficos Corporais/etiologia , Transtornos Dismórficos Corporais/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Tomografia por Emissão de Pósitrons , Sulfetos/farmacocinética , Adulto Jovem
15.
ACS Appl Mater Interfaces ; 11(7): 7192-7198, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30672273

RESUMO

A novel thermally activated delayed fluorescent (TADF) compound, 9-(3-((4,6-diphenyl-1,3,5-triazin-2-yl)oxy)phenyl)-3,6-diphenyl-9 H-carbazole (PhCz- o-Trz), with a donor-σ-acceptor (D-σ-A) motif is developed. A flexible small space σ-junction is adopted to partly suppress the intramolecular charge transfer (intra-CT) while inversely enhancing the intermolecular charge transfer (inter-CT) between D/A moieties, realizing the coexistence of both intra-CT and inter-CT in an amorphous aggregate. The coexistence of dual CTs increases the complexity of the singlet and triplet state mixing, enhancing the triplet-to-singlet spin-flip transition and thereby the TADF emission. Additionally, PhCz- o-Trz is evaluated not only as an emitter but also as a sensitizing host for fluorescent and phosphorescent dopants, all exhibiting high efficiencies with alleviated efficiency roll-offs. These results shed light on the development of new TADF materials with dual CTs and may further deepen our understanding about TADF mechanisms.

16.
Chemistry ; 24(65): 17293-17302, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30378204

RESUMO

A unique superparamagnetic-like behavior and a large "positive magneto-LC effect" were observed in the solid phases and the hexagonal columnar (Colh ) liquid crystalline (LC) phase, respectively, of novel achiral non-π-delocalized nitroxide diradical compounds (R,S)-1, which showed polymorphism in the solid phases (solids I and II). The SQUID magnetization measurement revealed that (1) (R,S)-1 containing a small amount of racemic diastereomers (R*,R*)-1 possessed an unusual and large temperature-independent magnetic susceptibility (χTIM >0) component in the original nanocrystalline solid I that was responsible for the observed superparamagnetic-like behavior under low magnetic fields and did not arise from the contamination by extrinsic magnetic metal or metal ion impurities, besides ordinary temperature-dependent paramagnetic susceptibility (χpara >0) and temperature-independent diamagnetic susceptibility (χdia <0) components, (2) a large increase in molar magnetic susceptibility (χM ) (positive magneto-LC effect) that occurred at the solid I-to-liquid crystal transition upon heating was preserved as an additional χTIM increase in the resulting polymorphic nanocrystalline solid II by cooling, and (3) such unique magnetic phenomena were induced by thermal processing for (R,S)-1 or by adding a small amount of (R*,R*)-1 to (R,S)-1 as the impurity.

17.
Yakugaku Zasshi ; 138(4): 533-536, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29608003

RESUMO

 This paper examines the reform experience of the 10th Annual Meeting of the Japanese Society for Pharmaceutical Palliative Care and Sciences from Instructional Systems perspectives, to check whether it was effective, efficient, and appealing for participants. "Instructional Systems" has been a research area in educational technology for the past 50 years, and has also been applied to training and human resource development in healthcare domains. If an annual meeting is to be designed for participants' learning, then perspectives of Instructional Systems can be applied to interpret the effort of the reform. First, fill in the gaps of participants' knowledge, using before-and-after comparison. Design a conference to meet the needs of its participants by checking why they attend (expectations) and what they bring in (starting status). Second, design the conference as a process of innovation. The bigger the expected changes, the more carefully participants should be prepared to accommodate them. Third, follow plan-do-check-action cycles with data for confirming and revising the new ways of running the meeting. Plan to check "exportability" of the new ways, to assess whether it can be generalized to future meetings.


Assuntos
Congressos como Assunto , Tecnologia Educacional , Cuidados Paliativos/organização & administração , Assistência Farmacêutica/organização & administração , Sociedades Farmacêuticas/organização & administração , Congressos como Assunto/tendências , Tecnologia Educacional/tendências , Humanos , Japão
18.
J Alzheimers Dis ; 61(4): 1355-1365, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29376856

RESUMO

BACKGROUND: The α7 subtype of the nicotinic acetylcholine receptor (nAChR) is considered important in higher cognitive functions, and cholinergic loss underpins the pathophysiology of Alzheimer's disease (AD). However, the relationships between α7 nAChR function and clinical functions or amyloid-ß (Aß) deposition remain to be explored in the living AD brain. OBJECTIVE: We aimed to elucidate the relationship between α7 nAChR availability in the specific cholinergic region and cognitive decline in the Aß-confirmed AD brain. METHODS: Twenty AD patients and ten age-matched healthy subjects were examined. The α7-nAChR availability and Aß deposition were evaluated using positron emission tomography with an α7 nAChR radiotracer 11C-(R)-MeQAA and 11C-Pittsburg compound B (11C-PiB), respectively. Semi-quantified values of tracer binding were estimated with a simplified reference tissue method for BPND of 11C-(R)-MeQAA and a tissue ratio method for SUVR of 11C-PiB. These parameters and clinical scores were compared voxel-wise using a statistical parametric mapping method. RESULTS: The levels of 11C-(R)-MeQAA BPND in the temporal and prefrontal cholinergic projection regions were significantly lower in AD, and negative correlations were found between 11C-PiB SUVR and 11C-(R)-MeQAA BPND in the region of the nucleus basalis magnocellularis and medial prefrontal cortex. Levels of 11C-(R)-MeQAA BPND were significantly correlated with memory and frontal function scores in AD. CONCLUSION: The association between Aß burden and α7-nAChR reduction in the basal forebrain cholinergic system was highlighted in relation to cognitive decline in AD. This suggests that Aß-linked α7-nAChR reduction is clinico-pathophyisologically important for considering a good therapeutic target in AD.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Adulto Jovem
19.
PLoS One ; 13(1): e0190991, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29309433

RESUMO

Schizophrenia and schizophrenia-like symptoms induced by the dopamine agonists and N-methyl-D aspartate type glutamate receptor antagonists occur only after the adolescent period. Similarly, animal models of schizophrenia by these drugs are also induced after the critical period around postnatal week three. Based upon the development-dependent onsets of these psychotomimetic effects, by using a DNA microarray technique, we identified the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes as novel candidates for schizophrenia-related molecules, whose mRNAs were up-regulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor. WDR3 and other related proteins are the nuclear proteins presumably involved in various cellular activities, such as cell cycle progression, signal transduction, apoptosis, and gene regulation. ALG1 is presumed to be involved in the regulation of the protein N-glycosylation. To further elucidate the molecular pathophysiology of schizophrenia, we have evaluated the genetic association of WDR3 and ALG1 in schizophrenia. We examined 21 single nucleotide polymorphisms [SNPs; W1 (rs1812607)-W16 (rs6656360), A1 (rs8053916)-A10 (rs9673733)] from these genes using the Japanese case-control sample (1,808 schizophrenics and 2,170 matched controls). No significant genetic associations of these SNPs were identified. However, we detected a significant association of W4 (rs319471) in the female schizophrenics (allelic P = 0.003, genotypic P = 0.008). Based on a haplotype analysis, the observed haplotypes consisting of W4 (rs319471)-W5 (rs379058) also displayed a significant association in the female schizophrenics (P = 0.016). Even after correction for multiple testing, these associations remained significant. Our findings suggest that the WDR3 gene may likely be a sensitive factor in female patients with schizophrenia, and that modification of the WDR3 signaling pathway warrants further investigation as to the pathophysiology of schizophrenia.


Assuntos
Manosiltransferases/genética , Proteínas Nucleares/genética , Adulto , Estudos de Casos e Controles , Epistasia Genética , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética
20.
J Am Chem Soc ; 139(51): 18480-18483, 2017 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-29185733

RESUMO

[10]Cycloparaphenylene ([10]CPP) and its tetraalkoxy derivatives were synthesized on the gram scale in 7 steps starting from 1,4-benzoquinone or 2,5-dialkoxy-1,4-benzoquinone. The key steps involve the highly cis-selective bis-addition of 4-bromo-4'-lithiobiphenyl to the quinones to produce a five-ring unit containing cyclohexa-1,4-diene-3,6-diol moiety, the platinum-mediated dimerization of the five-ring unit, and the H2SnCl4-mediated reductive aromatization of cyclohexadienediol. The tetraalkoxy substituents increased the solubility of [10]CPP in common organic solvents. The carrier-transport properties of thin films of [10]CPP and its derivatives were measured for the first time and indicated that [10]CPP derivatives could rival phenyl-C61-butyric acid methyl ester, which is used widely as an n-type active layer in bulk heterojunction photovoltaics.

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