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1.
Medicine (Baltimore) ; 100(35): e26961, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477126

RESUMO

BACKGROUND: The quantification of heterogeneity for the striatum and whole brain with F-18 FP-CIT PET images will be useful for diagnosis. The index obtained from texture analysis on PET images is related to pathological change that the neuronal loss of the nigrostriatal tract is heterogeneous according to the disease state. The aim of this study is to evaluate various heterogeneity indices of F-18 FP-CIT PET images in the diagnosis of Parkinson's disease (PD) patients and to access the diagnostic accuracy of the indices using machine learning (ML). METHODS: This retrospective study included F-18 FP-CIT PET images of 31 PD and 31 age-matched health controls (HC). The volume of interest was delineated according to iso-contour lines around standardized uptake value (SUV) 3.0 g/ml for each region of the striatum by PMod 3.603. One hundred eight heterogeneity indices were calculated using CGITA to find indices from which the PD and HC were classified using statistical significance. PD group was classified by constructing a 2-dimensional or 3-dimensional phase space quantifier using these heterogeneity indices. We used 71 heterogeneity indices to classify PD from HC using ML for dimensional reduction. RESULTS: The heterogeneity indices for classifying PD from HC were size-zone variability, contrast, inverse difference-moment, and homogeneity in the order of low P value. Three-dimensional quantifiers composed of normalized-contrast, code-similarity, and contrast were more clearly classified than 2-dimensional ones. After 71-dimensional reduction using PCA, classification was possible by logistic regression with 91.3% accuracy. The 2 groups were classified with an accuracy of 85.5% using the support vector machine and 88.4% using the random forest. The classification accuracy using the eXtreme Gradient Boosting was 95.7%, and feature importance was highest in order of SUV bias-corrected kurtosis, size-zone-variability, intensity-variability, and high-intensity-zone-variability. CONCLUSION: It was confirmed that PD patients is more clearly classified than the conventional 2-dimensional quantifier by introducing a 3-dimensional phase space quantifier. We observed that ML can be used to classify the 2 groups in an easy and explanatory manner. For the discrimination of the disease, 24 heterogeneity indices were found to be statistically useful, and the major cut-off values of 3 heterogeneity indices were size-zone variability (1906.44), intensity variability (129.21), and high intensity zone emphasis (800.29).


Assuntos
Doença de Parkinson/diagnóstico , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Idoso , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Neuroimagem/estatística & dados numéricos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Estudos Retrospectivos
2.
Nat Biomed Eng ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341536

RESUMO

Efficacious and accessible sources of natural killer (NK) cells would widen their use as immunotherapeutics, particularly for solid cancers. Here, we show that human somatic cells can be directly reprogrammed into NK cells with a CD56brightCD16bright phenotype using pluripotency transcription factors and an optimized reprogramming medium. The directly reprogrammed NK cells have strong innate-adaptive immunomodulatory activity and are highly potent against a wide range of cancer cells, including difficult-to-treat solid cancers and cancer stem cells. Both directly reprogrammed NK cells bearing a cancer-specific chimeric antigen receptor and reprogrammed NK cells in combination with antibodies competent for antibody-dependent cell-mediated cytotoxicity led to selective anticancer effects with augmented potency. The direct reprogramming of human somatic cells into NK cells is amenable to the production of autologous and allogeneic NK cells, and will facilitate the design and testing of cancer immunotherapies and combination therapies.

3.
Genes (Basel) ; 12(5)2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068253

RESUMO

Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 3' (15.2%) and 5' (12.8%) splice sites, and mutually exclusive exons (9.1%). Functional enrichment analysis showed that the differentially spliced genes (|FC| > 2 and BF > 20) were mainly enriched in functions associated with focal adhesion, extracellular exosomes, extracellular matrix organization, cell adhesion, and actin binding. Splice isoforms of selected genes including TRPT1, CNN2, and AP1G2, identified in sashimi plots, were further validated by RT-PCR analysis. This study provides valuable insight into the biology of iMSCs and the translation of mechanistic understanding of iMSCs into therapeutic applications.


Assuntos
Processamento Alternativo/genética , Células-Tronco Pluripotentes Induzidas/fisiologia , Células-Tronco Mesenquimais/fisiologia , Células Cultivadas , Regulação para Baixo/genética , Exossomos/genética , Matriz Extracelular/genética , Adesões Focais/genética , Expressão Gênica/genética , Humanos , Transcriptoma/genética , Regulação para Cima/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-34036782

RESUMO

A series of green-emitting fluorophores based on a tetra-azaacene core is synthesized by introducing nitrile substituents at different positions. Their molecular structure-optical property relationship [i.e., vibronic transitions in photoluminescence (PL) and electroluminescence (EL) spectra] is investigated to obtain a sharp emission where the vibronic peak ν0-0 should be intensified by suppressing ν0-n (n = 1, 2, 3...) transitions. The intensity ratios (I0-1/I0-0) of the ν0-1 and ν0-0 vibronic transitions in the PL spectra of DBBNP, DBBNP2CN1, and DBBNP2CN2 in hexane are 1.13, 0.80, and 0.67, respectively. Theoretical calculations explain that the CN substitution at positions 8 and 13 in DBBNP2CN2 induces a uniform charge distribution and reduces the Huang-Rhys factors (HRFs) of the vibrational normal modes coupled to the electronic transition. The organic light-emitting diode (OLED) fabricated with DBBNP2CN2 shows a narrower green EL emission at 518 nm with a smaller bandwidth (50 nm) than those of devices adopting DBBNP or DBBNP2CN1. The careful modification of the molecular structures and positions of substituents enables us to reduce the HRFs of vibrations to achieve a narrow emission bandwidth with decreased I0-1/I0-0, which suggests a design strategy to develop narrowband organic fluorophores to improve the color purity for wide-gamut OLED displays.

5.
Sci Rep ; 11(1): 4825, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649403

RESUMO

Our purpose in this study is to evaluate the clinical feasibility of deep-learning techniques for F-18 florbetaben (FBB) positron emission tomography (PET) image reconstruction using data acquired in a short time. We reconstructed raw FBB PET data of 294 patients acquired for 20 and 2 min into standard-time scanning PET (PET20m) and short-time scanning PET (PET2m) images. We generated a standard-time scanning PET-like image (sPET20m) from a PET2m image using a deep-learning network. We did qualitative and quantitative analyses to assess whether the sPET20m images were available for clinical applications. In our internal validation, sPET20m images showed substantial improvement on all quality metrics compared with the PET2m images. There was a small mean difference between the standardized uptake value ratios of sPET20m and PET20m images. A Turing test showed that the physician could not distinguish well between generated PET images and real PET images. Three nuclear medicine physicians could interpret the generated PET image and showed high accuracy and agreement. We obtained similar quantitative results by means of temporal and external validations. We can generate interpretable PET images from low-quality PET images because of the short scanning time using deep-learning techniques. Although more clinical validation is needed, we confirmed the possibility that short-scanning protocols with a deep-learning technique can be used for clinical applications.

6.
J Hazard Mater ; 409: 124516, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33243655

RESUMO

A low-density polyethylene (LDPE) degrading bacterial strain (ATKU1) was isolated (99.86% similar with Bacillus siamensis KCTC 13613T) from a plastic dumping site to study interactions between microplastics (< 5 mm) and microorganisms. The strain was found (by scanning electron microscopy) to form biofilm on the microplastic surface after its interaction with LDPE (avg. Mw~4,000 Da and avg. Mn~1,700 Da) as a sole carbon source. Atomic force microscopy (AFM) showed the biofilm's 3-D developmental patterns and significantly increased Young's modulus of the LDPE surface after microbial treatment. Most of the viable bacteria attached to biofilms rather than media, which suggested their ability to utilize LDPE. Absorption bands of carbonyl, alkenyl, acyl, ester, primary-secondary alcohol, alkene groups and nitric oxides were found on the treated LDPE particles using Fourier-transform infrared spectroscopy. Fourier transform-ion cyclotron resonance mass spectrometry of the media indicated compositional shifts of the compounds after treatment (i.e., increase in the degree of unsaturation and increment in oxygen-to-carbon ratio) and presence of unsaturated hydrocarbons, polyketides, terpenoids, aliphatic/peptides, dicarboxylic acids, lipid-like compounds were hinted. The plastic degrading abilities of Bacillus siamensis ATKU1 suggest its probable application for large scale plastic bioremediation facility.


Assuntos
Plásticos , Polietileno , Bacillus , Biofilmes , Microplásticos
7.
Adv Mater ; 32(51): e2002176, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32886378

RESUMO

Despite their low exciton-binding energies, metal halide perovskites are extensively studied as light-emitting materials owing to narrow emission with high color purity, easy/wide color tunability, and high photoluminescence quantum yields. To improve the efficiency of perovskite light-emitting diodes (PeLEDs), much effort has been devoted to controlling the emitting layer morphologies to induce charge confinement and decrease the nonradiative recombination. The interfaces between the emitting layer and charge transporting layer (CTL) are vulnerable to various defects that deteriorate the efficiency and stability of the PeLEDs. Therefore, the establishment of multifunctional CTLs that can improve not only charge transport but also critical factors that influence device performance, such as defect passivation, morphology/phase control, ion migration suppression, and light outcoupling efficiency, are highly required. Herein, the fundamental limitations of perovskites as emitters (i.e., defects, morphological and phase instability, high refractive index with poor outcoupling) and the recent developments with regard to multifunctional CTLs to compensate such limitations are summarized, and their device applications are also reviewed. Finally, based on the importance of multifunctional CTLs, the outlook and research prospects of multifunctional CTLs for the further improvement of PeLEDs are discussed.

8.
ACS Nano ; 14(10): 13246-13255, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-32910640

RESUMO

A series of poly(fluorene-co-phenylene)-based anionic conjugated polyelectrolytes (CPEs) are prepared with varying sizes of counterions (tetramethylammonium, tetraethylammonium, and tetrabutylammonium (TBA+)) and studied as a hole-transporting layer (HTL) for sky-blue-emissive perovskite light-emitting diodes (PeLEDs). Ionic CPE HTLs improve the wettability, compatibility, and nucleation of perovskite crystals at interfaces, enabling highly crystalline perovskite crystal growth with enhanced light-emitting properties. By incorporating the CPE HTLs containing bulky TBA+ counterions (MPS2-TBA) in place of PEDOT:PSS, the decreased phonon-electron coupling and increased exciton binding energy in perovskites are measured by temperature-dependent photoluminescence (PL) measurements. By increasing the size of counterions in CPE interlayers, the PL intensities and lifetimes of perovskite films increase. Through space-charge-limited current measurements, the lowest trap density is measured in the perovskite film on MPS2-TBA, emphasizing a critical role of larger counterions. Using density functional theory, MPS2-TBA is calculated to show the strongest adsorption affinity toward the interstitial defect of lead ions, explaining its pronounced interfacial defect passivation. The counterion size in CPE interlayers is interpreted as a main factor to determine the adsorption affinity onto perovskite, which determines the interacted area as noncovalent adsorption occurs. Finally, the sky-blue-emissive quasi-2D PeLED with MPS2-TBA shows the highest luminance efficiency (a peak EQE of 2.6% at 489 nm) and significantly improved spectral stability.

9.
ACS Appl Mater Interfaces ; 12(31): 35300-35310, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32654477

RESUMO

Organic polymers that exhibit features pertinent to functioning as host materials for thermally activated delayed fluorescence (TADF) emitters have considerable potential in solution-processable organic light-emitting diodes (OLEDs), allowing simple, low-cost, and large-area applications. In particular, polymer hosts have superior characteristics, including facile functionality to introduce various electron donor and acceptor entities, the ability to uniformly disperse and contain small molecular dopants, and the ability to produce more smooth and homogeneous films, compared to those of their small-molecule counterparts. This manuscript describes the design and development of three new styrene-based copolymers (ABP91, ABP73, and ABP55) bearing diphenylacridine as the electron donor and 2,12-di-tert-butyl-7-phenyl-5,9-dioxa-13b-boranaphtho[3,2,1-de]anthracene as the electron acceptor. In particular, ABP91, ABP73, and ABP55 were synthesized via variations in the ratio of donor to acceptor monomers to substantiate their influence in OLED applications. With the ability of the styrene backbone of interrupting the direct electronic coupling between the adjacent electron donor and acceptor entities through non-conjugated linkages, high triplet energy can be inherited by the resulting polymers (>2.70 eV). Furthermore, these materials manifest thermal robustness through high decomposition temperatures (between 348 and 366 °C) and high glass transition temperatures (between 234 and 277 °C). Consequently, solution-processable OLEDs fabricated using the newly synthesized copolymers as host materials and the familiar t4CzIPN as a green-emissive TADF dopant deliver state-of-the-art performance with maximum external quantum efficiencies of 21.8, 22.2, and 19.7% for ABP91, ABP73, and ABP55, respectively. To our knowledge, this is, to date, the best performance reported when organic polymers are used as host materials in solution-processable TADF OLEDs. The pragmatic outcomes obtained in this study can provide useful insights into the structure-property relationship to the OLED community for the further development of efficient polymer hosts for use in solution-processable TADF OLEDs.

10.
Stem Cell Res Ther ; 11(1): 257, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32586386

RESUMO

BACKGROUND: Schwann cells (SCs) are primarily responsible for regeneration and repair of the peripheral nervous system (PNS). Renewable and lineage-restricted SC precursors (SCPs) are considered highly desirable and promising cell sources for the production of SCs and for studies of SC lineage development, but SCPs are extremely limited. Here, we present a novel direct conversion strategy for the generation of human SCPs, capable of differentiating into functional SCs. METHODS: Easily accessible human skin fibroblast cells were directly induced into integration-free SCPs using episomal vectors (Oct3/4, Klf4, Sox2, L-Myc, Lin28 and p53 shRNA) under SCP lineage-specific chemically defined medium conditions. Induced SCPs (iSCPs) were further examined for their ability to differentiate into SCs. The identification and functionality of iSCPs and iSCP-differentiated SCs (iSCs) were confirmed according to morphology, lineage-specific markers, neurotropic factor secretion, and/or standard functional assays. RESULTS: Highly pure, Sox 10-positive of iSCPs (more than 95% purity) were generated from human skin fibroblasts within 3 weeks. Established iSCPs could be propagated in vitro while maintaining their SCP identity. Within 1 week, iSCPs could efficiently differentiate into SCs (more than 95% purity). The iSCs were capable of secreting various neurotrophic factors such as GDNF, NGF, BDNF, and NT-3. The in vitro myelinogenic potential of iSCs was assessed by myelinating cocultures using mouse dorsal root ganglion (DRG) neurons or human induced pluripotent stem cell (iPSC)-derived sensory neurons (HSNs). Furthermore, iSC transplantation promoted sciatic nerve repair and improved behavioral recovery in a mouse model of sciatic nerve crush injury in vivo. CONCLUSIONS: We report a robust method for the generation of human iSCPs/iSCs that might serve as a promising cellular source for various regenerative biomedical research and applications, such as cell therapy and drug discovery, especially for the treatment of PNS injury and disorders.


Assuntos
Células-Tronco Pluripotentes Induzidas , Traumatismos dos Nervos Periféricos , Animais , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos , Regeneração Nervosa , Células de Schwann , Nervo Isquiático
11.
J Hum Genet ; 65(6): 551-555, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32144408

RESUMO

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, especially in males. Females with FXS tend to be relatively mildly affected because of compensation by a second X chromosome with a normal FMR1 gene. In most cases, FXS is caused by an expansion of the CGG repeats (>200 triplets, full mutation, FM) in the 5'-untranslated region of the FMR1 gene. Premutation alleles (PM, 55-200 repeats), usually lack the clinical features of FXS, are highly unstable when transmitted to offspring and can give rise to FM, especially in female meiosis. We describe a 3-year-old girl with typical FXS, with only a fully expanded FMR1 allele (288 CGG repeats) due to uniparental isodisomy of X chromosome, inherited from mother carrying a premutation allele. The patient's FMR1 methylation region is completely methylated due to full mutation of CGG repeat. This unusual and rare case indicates the importance of a detailed genomic approach to explain nontraditional Mendelian inheritance pattern.


Assuntos
Cromossomos Humanos X/genética , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Deficiência Intelectual/genética , Alelos , Pré-Escolar , Metilação de DNA/genética , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/patologia , Humanos , Deficiência Intelectual/patologia , Mutação/genética , Fenótipo , Dissomia Uniparental/genética , Dissomia Uniparental/patologia
12.
PLoS One ; 15(3): e0229860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134983

RESUMO

PURPOSE: We have evaluated the clinical significance of the washout rate (WR) on I-123 MIBG scans through the analysis of the relationship between the I-123 MIBG scans and autonomic status in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Sixty patients with clinical PD who had decreased HMR were enrolled. An autonomic symptom was evaluated using a head-up tilt test and the Composite Autonomic Severity Score (CASS). An I-123 MIBG scan and F-18 FP-CIT positron emission tomography (PET) were performed. All of the patients were classified into three groups according to the WR. The differences in patient characteristics and the imaging parameters among the three groups were evaluated, and a correlation analysis was also performed. RESULTS: The frequency of orthostatic hypotension was significantly different among the three groups. The difference in systolic pressure (dSysPr) and the difference in diastolic pressure (dDiaPr) of group 3 was significantly larger than those of groups 1 and 2. From the correlation analysis, it can be seen that age, Hoehn and Yahr (H&Y) stage, dSysPr, and dDiaPr had a weak positive correlation with the WR. The total CASS score was significantly higher in group 3 compared with groups 1 and 2. The WR had a moderate positive correlation with the cardiosympathetic score and the total CASS score. CONCLUSION: The WR is related to autonomic dysfunction. An I-123 MIBG cardiac scan is considered to be a good method to evaluate not only the differential diagnosis of Parkinson's disease but also the degree of autonomic dysfunction.


Assuntos
3-Iodobenzilguanidina/administração & dosagem , Sistema Nervoso Autônomo/diagnóstico por imagem , Radioisótopos do Iodo/administração & dosagem , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/administração & dosagem , 3-Iodobenzilguanidina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Radioisótopos de Flúor/administração & dosagem , Radioisótopos de Flúor/metabolismo , Coração/diagnóstico por imagem , Humanos , Hipotensão Ortostática/diagnóstico , Radioisótopos do Iodo/metabolismo , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Tropanos/administração & dosagem , Tropanos/metabolismo
13.
Front Chem ; 8: 61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117885

RESUMO

Organic entities that can transport electrons are seldom available to develop adequate bipolar host materials applicable for solution-processable thermally activated delayed fluorescence (TADF)-organic light-emitting diodes (OLEDs). Therefore, the introduction of new electron-affine entities that plausibly demonstrate high triplet energy (E T) is of urgent need. In this contribution, we introduced benzimidazo[1,2-a][3,1]benzothiazine (BBIT) as a novel electron-affine entity and developed two new bipolar host materials, CzBBIT and 2CzBBIT. Both host materials exhibit high E T of 3.0 eV, superior thermal robustness with the thermal decomposition temperature of up to 392°C, a glass transition temperature of up to 161°C, and high solubility in common organic solvents. Consequently, the solution-processable OLEDs fabricated using a recognized IAcTr-out as the green TADF emitter doped into CzBBIT as the host, realized a maximum external quantum efficiency (EQE) of 23.3%, while the 2CzBBIT:IAcTr-out blend film-based device displayed an EQE of 18.7%. These outcomes corroborated that this work could shed light on the scientific community on the design of new electron-affine entities to establish the effective use of bipolar host materials toward proficient solution-processable TADF-OLEDs.

14.
Photochem Photobiol ; 96(4): 834-844, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32083762

RESUMO

We report a Förster resonance energy transfer (FRET)-based imaging ensemble for the visualization of membrane potential in living cells. A water-soluble poly(fluorene-cophenylene) conjugated polyelectrolyte (FsPFc10) serves as a FRET donor to a voltage-sensitive dye acceptor (FluoVolt™ ). We observe FRET between FsPFc10 and FluoVolt™ , where the enhancement in FRET-sensitized emission from FluoVolt™ is measured at various donor/acceptor ratios. At a donor/acceptor ratio of 1, the excitation of FluoVolt™ in a FRET configuration results in a three-fold enhancement in its fluorescence emission (compared to when it is excited directly). FsPFc10 efficiently labels the plasma membrane of HEK 293T/17 cells and remains resident with minimal cellular internalization for ~ 1.5 h. The successful plasma membrane-associated colabeling of the cells with the FsPFc10-FluoVolt™ donor-acceptor pair is confirmed by dual-channel confocal imaging. Importantly, cells labeled with FsPFc10 show excellent cellular viability with no adverse effect on cell membrane depolarization. During depolarization of membrane potential, HEK 293T/17 cells labeled with the donor-acceptor FRET pair exhibit a greater fluorescence response in FluoVolt™ emission relative to when FluoVolt™ is used as the sole imaging probe. These results demonstrate the conjugated polyelectrolyte to be a new class of membrane labeling fluorophore for use in voltage sensing schemes.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Potenciais da Membrana , Polieletrólitos/química , Ânions/química , Membrana Celular/química , Corantes Fluorescentes/química , Células HEK293 , Humanos , Técnicas de Patch-Clamp
15.
ACS Appl Mater Interfaces ; 12(10): 12328-12336, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31997636

RESUMO

The open-circuit voltage (Voc) of perovskite photovoltaic diodes depends largely on the selection of charge transport layers (CTLs) and surface passivation, which makes it important to understand the physical processes occurring at the interface between the perovskite and a CTL. We provide a direct correlation between Voc and the interfacial characteristics of perovskites tuned through stoichiometry engineering of precursor solutions and surface modification of the underlying poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) layer. Poor quality interfacial perovskite crystals were observed on top of the PEDOT:PSS layer, resulting in strong interfacial recombination and a low Voc. In contrast, the growth of the interfacial perovskite crystals was significantly improved by the synergic effects of varying the precursor solution composition and covering the surface with a pH-neutral conjugated polyelectrolyte, poly[2,6-(4,4-bis(potassium butanylsulfonate)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (CPE-K), which possesses potassium ions as counter ions. The influence of the energy-level alignment at the interface on Voc was also discussed. Our findings highlight that improved perovskite crystallization at the interface can facilitate bulk growth of perovskite grains in the vertical direction and effectively suppress nonradiative surface charge recombination, thus enhancing the short-circuit current and Voc.

16.
ACS Appl Mater Interfaces ; 12(7): 8485-8494, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31990169

RESUMO

Recently, various host materials have been developed for solution-processed thermally activated delayed fluorescent organic light-emitting diodes (TADF-OLEDs). Compared with small-molecule hosts, polymeric hosts are advantageous for inducing a uniform distribution and segregation of dopant molecules in the emissive layer without undesired large-scale phase separation. In this study, new polymer hosts were demonstrated, in which a bipolar conjugative moiety consisting of a carbazole (Cz) donor and an α-carboline (α-Cb) acceptor was bound to the polystyrene backbone through a non-conjugated linker. They exhibited high triplet energies of >2.8 eV, and their emission spectra overlapped with the absorption spectrum of a green TADF emitter, which allowed facile energy transfer from the polymeric host to the small-molecule dopants. High device performance was observed, with external quantum efficiencies (EQEs) of 13.65, 17.09, and 17.48% for solution-processed green TADF-OLEDs using PSCzCz, PSCzCb, and PSCbCz, respectively, as hosts for the EML. The EQEs of bipolar host (PSCzCb and PSCbCz)-based devices were higher than those of unipolar host (poly(N-vinylcarbazole) and PSCzCz)-based devices owing to the well-balanced charge-carrier transport. According to these results, the polymeric host bearing a bipolar Cz and α-Cb coupled moiety is a promising material for solution-processable TADF-OLEDs.

17.
Dev Dyn ; 249(5): 646-655, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31872525

RESUMO

BACKGROUND: Dysfunction of GABAergic and glutamatergic neurons in the brain, which establish inhibitory and excitatory networks, respectively, may cause diverse neurological disorders. The mechanism underlying the determination of GABAergic vs. glutamatergic neurotransmitter phenotype in the caudal diencephalon remains largely unknown. RESULTS: In this study, we investigated the consequence of Tcf7l2 (transcription factor 7-like 2) ablation on the neurotransmitter identity of GABAergic and glutamatergic neurons in the caudal diencephalon. We identified positive and negative activity in the control of glutamatergic and GABAergic neuronal gene expression by Tcf7l2. Loss of Tcf7l2 did not alter the initial acquisition of the neurotransmitter identity in thalamic neurons. However, glutamatergic thalamic neurons failed to maintain their excitatory neurotransmitter phenotype in the absence of Tcf7l2. Moreover, a subset of Tcf7l2-deficient thalamic neurons underwent a glutamatergic to GABAergic neurotransmitter identity switch. Our data indicate that Tcf7l2 may promote glutamatergic neuronal differentiation and repress GABAergic neurotransmitter identity in the caudal thalamus. CONCLUSIONS: This study provides evidence for a novel and crucial role of Tcf7l2 in the molecular mechanism by which the neurotransmitter identity of glutamatergic thalamic neurons is established. Our findings exemplify a clear case of neurotransmitter identity regulation that is partitioned into initiation and maintenance phases.

18.
Chem Commun (Camb) ; 55(86): 12952-12955, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31602441

RESUMO

This study reports the design, synthesis, and characterization of two new bipolar host materials, DCzCP and TCzCP. Both materials were implemented as hosts by doping a known green thermally activated delayed fluorescent (TADF) emitter (t4CzIPN) in solution-processable OLEDs. DCzCP-based devices afford the best performance with the maximum external quantum efficiency (EQE) of 21.2%. Notably, the EQE was maintained at 20.7% and 19.7% at a practical luminance of 500 cd m-2 and 1000 cd m-2, respectively, demonstrating very small roll-off.

19.
J Proteome Res ; 18(12): 4133-4142, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31612721

RESUMO

Next-generation genome sequencing has enabled the discovery of numerous disease- or drug-response-associated nonsynonymous single nucleotide variants (nsSNVs) that alter the amino acid sequences of a protein. Although several studies have attempted to characterize pathogenic nsSNVs, few have been confirmed as single amino acid variants (SAAVs) at the protein level. Here we developed the SAAVpedia platform to identify, annotate, and retrieve pathogenic SAAV candidates from proteomic and genomic data. The platform consists of four modules: SAAVidentifier, SAAVannotator, SNV/SAAVretriever, and SAAVvisualizer. The SAAVidentifier provides a reference database containing 18 206 090 SAAVs and performs the identification and quality assessment of SAAVs. The SAAVannotator provides functional annotation with biological, clinical, and pharmacological information for the interpretation of condition-specific SAAVs. The SNV/SAAVretriever module enables bidirectional navigation between relevant SAAVs and nsSNVs with diverse genomic and proteomic data. SAAVvisualizer provides various statistical plots based on functional annotations of detected SAAVs. To demonstrate the utility of SAAVpedia, the proteogenomic pipeline with protein-protein interaction network analysis was applied to proteomic data from breast cancer and glioblastoma patients. We identified 1326 and 12 breast-cancer- and glioblastoma-related genes that contained one or more SAAVs, including BRCA2 and FAM49B, respectively. SAAVpedia is a suitable platform for confirming whether a genomic variant is maintained in an amino acid sequence. Furthermore, as a result of the SAAV discovery of these positive controls, the SAAVpedia could play a key role in the protein functional study for the Human Proteome Project (HPP).


Assuntos
Bases de Dados de Proteínas , Proteínas/genética , Proteogenômica/métodos , Aminoácidos/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Visualização de Dados , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Anotação de Sequência Molecular , Proteínas/metabolismo , Interface Usuário-Computador
20.
Ann Pediatr Endocrinol Metab ; 24(2): 137-141, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261480

RESUMO

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)2D3 level (11.2 pg/mL), and normal 25(OH)D3 level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both <3rd percentile). The Bayley Scales of Infant and Toddler Development II indicated significantly delayed development (mental development index <50, psychomotor development index <50). The patient was a compound heterozygous for two novel pathogenic variants in the CYP27B1 gene: c.57_69del (p.Glu20Profs*2) and c.171dupG (p.Leu58Alafs*275), inherited from his mother and father, respectively. The patient showed remarkable improvement after treatment with calcitriol and calcium carbonate.

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