Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Adv ; 10(11): eadi1863, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489366

RESUMO

Thyroid hormone (TH) imbalance is linked to the pathophysiology of reversible dementia and Alzheimer's disease (AD). It is unclear whether tissue hypothyroidism occurs in the AD brain and how it affects on AD pathology. We find that decreased iodothyronine deiodinase 2 is correlated with hippocampal hypothyroidism in early AD model mice before TH alterations in the blood. TH deficiency leads to spontaneous activation of microglia in wild-type mice under nonstimulated conditions, resulting in lowered innate immune responses of microglia in response to inflammatory stimuli or amyloid-ß. In AD model mice, TH deficiency aggravates AD pathology by reducing the disease-associated microglia population and microglial phagocytosis. We find that TH deficiency reduces microglial ecto-5'-nucleotidase (CD73) and inhibition of CD73 leads to impaired innate immune responses in microglia. Our findings reveal that TH shapes microglial responses to inflammatory stimuli including amyloid-ß, and brain hypothyroidism in early AD model mice aggravates AD pathology by microglial dysfunction.


Assuntos
Doença de Alzheimer , Hipotireoidismo , Camundongos , Animais , Doença de Alzheimer/patologia , Microglia/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Imunidade Inata , Modelos Animais , Modelos Animais de Doenças
2.
Hum Genomics ; 17(1): 96, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37898819

RESUMO

BACKGROUND: Fragmentomics, the investigation of fragmentation patterns of cell-free DNA (cfDNA), has emerged as a promising strategy for the early detection of multiple cancers in the field of liquid biopsy. However, the clinical application of this approach has been hindered by a limited understanding of cfDNA biology. Furthermore, the prevalence of hematopoietic cell-derived cfDNA in plasma complicates the in vivo investigation of tissue-specific cfDNA other than that of hematopoietic origin. While conventional two-dimensional cell lines have contributed to research on cfDNA biology, their limited representation of in vivo tissue contexts underscores the need for more robust models. In this study, we propose three-dimensional organoids as a novel in vitro model for studying cfDNA biology, focusing on multifaceted fragmentomic analyses. RESULTS: We established nine patient-derived organoid lines from normal lung airway, normal gastric, and gastric cancer tissues. We then extracted cfDNA from the culture medium of these organoids in both proliferative and apoptotic states. Using whole-genome sequencing data from cfDNA, we analyzed various fragmentomic features, including fragment size, footprints, end motifs, and repeat types at the end. The distribution of cfDNA fragment sizes in organoids, especially in apoptosis samples, was similar to that found in plasma, implying occupancy by mononucleosomes. The footprints determined by sequencing depth exhibited distinct patterns depending on fragment sizes, reflecting occupancy by a variety of DNA-binding proteins. Notably, we discovered that short fragments (< 118 bp) were exclusively enriched in the proliferative state and exhibited distinct fragmentomic profiles, characterized by 3 bp palindromic end motifs and specific repeats. CONCLUSIONS: In conclusion, our results highlight the utility of in vitro organoid models as a valuable tool for studying cfDNA biology and its associated fragmentation patterns. This, in turn, will pave the way for further enhancements in noninvasive cancer detection methodologies based on fragmentomics.


Assuntos
Ácidos Nucleicos Livres , Neoplasias , Humanos , Ácidos Nucleicos Livres/genética , Neoplasias/genética , Biópsia Líquida , Sequenciamento Completo do Genoma , Linhagem Celular , Biomarcadores Tumorais/genética
3.
Sci Adv ; 9(35): eadh8619, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37656783

RESUMO

Phototherapeutics has shown promise in treating various diseases without surgical or drug interventions. However, it is challenging to use it in inner-body applications due to the limited light penetration depth through the skin. Therefore, we propose an organic light-emitting diode (OLED) catheter as an effective photobiomodulation (PBM) platform useful for tubular organs such as duodenums. A fully encapsulated highly flexible OLED is mounted over a round columnar structure, producing axially uniform illumination without local hotspots. The biocompatible and airtight OLED catheter can operate in aqueous environments for extended periods, meeting the essential requirements for inner-body medical applications. In a diabetic Goto-Kakizaki (GK) rat model, the red OLED catheter delivering 798 mJ of energy is shown to reduce hyperglycemia and insulin resistance compared to the sham group. Results are further supported by the subdued liver fibrosis, illustrating the immense potential of the OLED-catheter-based internal PBM for the treatment of type 2 diabetes and other diseases yet to be identified.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Animais , Ratos , Catéteres , Diabetes Mellitus Tipo 2/terapia , Duodeno , Hiperglicemia/terapia , Fototerapia
4.
Exp Mol Med ; 55(8): 1831-1842, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37582976

RESUMO

We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.


Assuntos
Células Epiteliais , Pulmão , Humanos , Células Epiteliais/metabolismo , Epitélio , Diferenciação Celular/fisiologia , Organoides
5.
Sci Adv ; 9(22): eadf1388, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37256963

RESUMO

Boron-based compounds exhibiting a multiresonance thermally activated delayed fluorescence are regarded promising as a narrowband blue emitter desired for efficient displays with wide color gamut. However, their planar nature makes them prone to concentration-induced excimer formation that broadens the emission spectrum, making it hard to increase the emitter concentration without raising CIE y coordinate. To overcome this bottleneck, we here propose o-Tol-ν-DABNA-Me, wherein sterically hindered peripheral phenyl groups are introduced to reduce intermolecular interactions, leading to excimer formation and thus making the pure narrowband emission character far less sensitive to concentration. With this approach, we demonstrate deep-blue OLEDs with y of 0.12 and full width at half maximum of 18 nm, with maximum external quantum efficiency (EQE) of ca. 33%. Adopting a hyperfluorescent architecture, the OLED performance is further enhanced to EQE of 35.4%, with mitigated efficiency roll-off, illustrating the immense potential of the proposed method for energy-efficient deep-blue OLEDs.

6.
Mol Cancer Res ; 21(7): 726-740, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37040163

RESUMO

Patients with triple-negative breast cancer (TNBC) often develop metastases in visceral organs including the liver, but the detailed molecular mechanisms of TNBC liver metastasis is not clearly understood. In this study, we tried to dissect the process of premetastatic niche formation in the liver by using patient-derived xenograft (PDX) models of TNBC with different metastatic propensity. RNA sequencing of TNBC PDX models that successfully metastasized to liver showed upregulation of the Cx3cr1 gene in the liver microenvironment. In syngeneic breast cancer models, the Cx3cr1 upregulation in liver preceded the development of cancer cell metastasis and was the result of recruitment of CX3CR1-expressing macrophages. The recruitment was induced by the CX3CL1 production from the liver endothelial cells and this CX3CL1-CX3CR1 signaling in the premetastatic niche resulted in upregulation of MMP9 that promoted macrophage migration and cancer cell invasion. In addition, our data suggest that the extracellular vesicles derived from the breast cancer cells induced the TNFα expression in liver, which leads to the CX3CL1 upregulation. Lastly, the plasma CX3CL1 levels in 155 patients with breast cancer were significantly associated with development of liver metastasis. IMPLICATIONS: Our data provides previously unknown cascades regarding the molecular education of premetastatic niche in liver for TNBC.


Assuntos
Vesículas Extracelulares , Neoplasias Hepáticas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Células Endoteliais/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/metabolismo , Vesículas Extracelulares/metabolismo , Microambiente Tumoral
7.
J Breast Cancer ; 26(1): 60-76, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36762781

RESUMO

PURPOSE: Patients with triple-negative breast cancer (TNBC) have an increased risk of distant metastasis compared to those with other subtypes. In this study, we aimed to identify the genes associated with distant metastasis in TNBC and their underlying mechanisms. METHODS: We established patient-derived xenograft (PDX) models using surgically resected breast cancer tissues from 31 patients with TNBC. Among these, 15 patients subsequently developed distant metastases. Candidate metastasis-associated genes were identified using RNA sequencing. In vitro wound healing, proliferation, migration, and invasion assays and in vivo tumor xenograft and metastasis assays were performed to determine the functional importance of aldo-keto reductase family 1 member C2 (AKR1C2). Additionally, we used the METABRIC dataset to investigate the potential role of AKR1C2 in regulating TNBC subtypes and their downstream signaling activities. RESULTS: RNA sequencing of primary and PDX tumors showed that genes involved in steroid hormone biosynthesis, including AKR1C2, were significantly upregulated in patients who subsequently developed metastasis. In vitro and in vivo assays showed that silencing of AKR1C2 resulted in reduced cell proliferation, migration, invasion, tumor growth, and incidence of lung metastasis. AKR1C2 was upregulated in the luminal androgen receptor (LAR) subtype of TNBC in the METABRIC dataset, and AKR1C2 silencing resulted in the downregulation of LAR classifier genes in TNBC cell lines. The androgen receptor (AR) gene was a downstream mediator of AKR1C2-associated phenotypes in TNBC cells. AKR1C2 expression was associated with gene expression pathways that regulate AR expression, including JAK-STAT signaling or interleukin 6 (IL-6). The levels of phospho-signal transducer and activator of transcription and IL-6, along with secreted IL-6, were significantly downregulated in AKR1C2-silenced TNBC cells. CONCLUSION: Our data indicate that AKR1C2 is an important regulator of cancer growth and metastasis in TNBC and may be a critical determinant of LAR subtype features.

8.
Sci Rep ; 13(1): 1369, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697452

RESUMO

Near-infrared organic light-emitting diodes (NIR OLEDs) with heavy metals are regularly reported due to the advantages of their various applications in healthcare services, veil authentication, and night vision displays. For commercial applications, it is necessary to look at radiance capacity (RC) instead of radiance because of power consumption. However, recent papers still reported only simple high radiance performance and do not look at device from the point of view of RC. To overcome this hurdle, we designed Ir(III)-based heteroleptic NIR materials with two types of auxiliary ligand. The proposed emitters achieve a highly oriented horizontal dipole ratio (Ir(mCPDTiq)2tmd, complex 1: 80%, Ir(mCPDTiq)2acac, complex 2: 81%) with a short radiative lifetime (1: 386 ns, 2: 323 ns). The device also shows an extremely low turn-on voltage (Von) of 2.2 V and a high RC of 720 mW/sr/m2/V. The results on the Von and RC of the device is demonstrated an outstanding performance among the Ir(III)-based NIR OLEDs with a similar emission peak.

9.
Br J Cancer ; 128(4): 626-637, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36522480

RESUMO

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT.


Assuntos
Neoplasias da Mama , Neoplasias Fibroepiteliais , Tumor Filoide , Humanos , Animais , Camundongos , Feminino , Fosfatidilinositol 3-Quinases , Linhagem Celular Tumoral , Mesilato de Imatinib , Neoplasias da Mama/patologia , Tumor Filoide/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Mamíferos
10.
BMC Bioinformatics ; 23(1): 157, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501695

RESUMO

BACKGROUND: Although single-cell RNA sequencing of xenograft samples has been widely used, no comprehensive bioinformatics pipeline is available for human and mouse mixed single-cell analyses. Considering the numerous homologous genes across the human and mouse genomes, misalignment errors should be evaluated, and a new algorithm is required. We assessed the extents and effects of misalignment errors and exonic multi-mapping events when using human and mouse combined reference data and developed a new bioinformatics pipeline with expression-based species deconvolution to minimize errors. We also evaluated false-positive signals presumed to originate from ambient RNA of the other species and address the importance to computationally remove them. RESULT: Error when using combined reference account for an average of 0.78% of total reads, but such reads were concentrated to few genes that were greatly affected. Human and mouse mixed single-cell data, analyzed using our pipeline, clustered well with unmixed data and showed higher k-nearest-neighbor batch effect test and Local Inverse Simpson's Index scores than those derived from Cell Ranger (10 × Genomics). We also applied our pipeline to multispecies multisample single-cell library containing breast cancer xenograft tissue and successfully identified all samples using genomic array and expression. Moreover, diverse cell types in the tumor microenvironment were well captured. CONCLUSION: We present our bioinformatics pipeline for mixed human and mouse single-cell data, which can also be applied to pooled libraries to obtain cost-effective single-cell data. We also address misalignment, multi-mapping error, and ambient RNA as a major consideration points when analyzing multispecies single-cell data.


Assuntos
Biologia Computacional , Genoma , Algoritmos , Animais , Genômica , Humanos , Camundongos , RNA
11.
ACS Appl Mater Interfaces ; 13(38): 45778-45788, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34519475

RESUMO

The design of robust boron acceptors plays a key role in the development of boron-based thermally activated delayed fluorescence (TADF) emitters for the realization of efficient and stable blue organic light-emitting diodes (OLEDs). Herein, we report a set of donor (D)-acceptor (A)-type blue TADF compounds (1-3) comprising triply bridged triarylboryl acceptors, the so-called B-heterotriangulenes, which differ depending on the identity of one of the bridging groups: methylene (1), dimethylmethylene (2), or oxo (3). The X-ray crystal structures of 2 and 3 reveal a highly twisted D-A connectivity and a completely planar geometry for the B-heterotriangulene rings. All compounds exhibit blue emissions with the unitary photoluminescence quantum yields and small singlet-triplet energy splitting (<0.1 eV) in their doped host films. The compounds exhibit a fast reverse intersystem crossing rate (kRISC ≈ 106 s-1) with short-lived delayed fluorescence (τd ≈ 2 µs), which is found to be promoted by the strong spin-orbit coupling between the local triplet excited state (3LE, T2) and singlet (S1) states. Using compounds 1-3 as the emitters, highly efficient blue TADF-OLEDs are realized. The devices based on the emitters with B-heterotriangulenes exhibit better performances than the device incorporating a singly bridged reference emitter over the whole luminance range. Notably, the device based on the fully dimethylmethylene-bridged emitter (2) achieves the highest maximum external quantum efficiency (EQE) of 28.2% and the lowest efficiency roll-off, maintaining a high EQE value of 21.2% at 1000 cd/m2.

12.
Nat Commun ; 12(1): 4840, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376661

RESUMO

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Adenocarcinoma/genética , Animais , Feminino , Fluoruracila/administração & dosagem , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Oxaliplatina/administração & dosagem , Neoplasias Gástricas/genética , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
13.
Sci Rep ; 11(1): 2310, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504853

RESUMO

Vertical sleeve gastrectomy (VSG) is the most commonly performed bariatric/metabolic surgery, exhibiting a high rate of diabetes remission in humans. To elucidate the molecular mechanisms of VSG, we performed transcriptomic analysis of the liver, fat, and muscle in VSG mice. C57BL/6 mice fed a high-fat diet were randomly assigned to sham or VSG surgery. The sham-operated mice were fed ad libitum (sham group) or pair-fed (sham-PF group) matching their food intake to the VSG-operated mice. Comparative transcriptomic analysis of the liver, fat, and muscle using RNA sequencing was performed. VSG reduced body weight and improved glucose tolerance compared to the sham group, but not more than the sham-PF group. Improvement in fatty liver and adipose tissue inflammation was comparable between VSG and sham-PF. However, global gene expression profiles showed distinctive changes in the liver, fat, and muscle of the VSG group compared to both the sham or sham-PF groups. The liver showed the most prominent gene expression changes. Immune response-related pathways were commonly upregulated in the three organs of the VSG group compared to the sham or sham-PF. VSG induces organ-specific gene expression changes in the liver, fat, and muscle, which may play critical roles in metabolic improvements after VSG.


Assuntos
Fígado/metabolismo , Músculos/metabolismo , Animais , Peso Corporal/fisiologia , Gastrectomia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Insulina/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculos/efeitos dos fármacos , Análise de Sequência de RNA , Transcriptoma/genética
14.
Sensors (Basel) ; 22(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35009644

RESUMO

The acquisition of physiological data are essential to efficiently predict and treat cardiac patients before a heart attack occurs and effectively expedite motor recovery after a stroke. This goal can be achieved by using wearable wireless sensor network platforms for real-time healthcare monitoring. In this paper, we present a wireless physiological signal acquisition device and a smartphone-based software platform for real-time data processing and monitor and cloud server access for everyday ECG/EMG signal monitoring. The device is implemented in a compact size (diameter: 30 mm, thickness: 4.5 mm) where the biopotential is measured and wirelessly transmitted to a smartphone or a laptop for real-time monitoring, data recording and analysis. Adaptive digital filtering is applied to eliminate any interference noise that can occur during a regular at-home environment, while minimizing the data process time. The accuracy of ECG and EMG signal coverage is assessed using Bland-Altman analysis by comparing with a reference physiological signal acquisition instrument (RHS2116 Stim/Recording System, Intan). Signal coverage of R-R peak intervals showed almost identical outcome between this proposed work and the RHS2116, showing a mean difference in heart rate of 0.15 ± 4.65 bpm and a Wilcoxon's p value of 0.133. A 24 h continuous recording session of ECG and EMG is conducted to demonstrate the robustness and stability of the device based on extended time wearability on a daily routine.


Assuntos
Dispositivos Eletrônicos Vestíveis , Atenção à Saúde , Eletrocardiografia , Ambiente Domiciliar , Humanos , Monitorização Fisiológica , Processamento de Sinais Assistido por Computador
15.
Sensors (Basel) ; 20(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023223

RESUMO

With the growing interest in big data technology, mobile IoT devices play an essential role in data collection. Generally, IoT sensor nodes are randomly distributed to areas where data cannot be easily collected. Subsequently, when data collection is impossible (i.e., sensing holes occurrence situation) due to improper placement of sensors or energy exhaustion of sensors, the sensors should be relocated. The cluster header in the sensing hole sends requests to neighboring cluster headers for the sensors to be relocated. However, it can be possible that sensors in the specific cluster zones near the sensing hole are continuously requested to move. With this knowledge, there can be a ping-pong problem, where the cluster headers in the neighboring sensing holes repeatedly request the movement of the sensors in the counterpart sensing hole. In this paper, we first proposed the near-uniform selection and movement scheme of the sensors to be relocated. By this scheme, the energy consumption of the sensors can be equalized, and the sensing capability can be extended. Thus the network lifetime can be extended. Next, the proposed relocation protocol resolves a ping-pong problem using queues with request scheduling. Another crucial contribution of this paper is that performance was analyzed using the fully-customed OMNeT++ simulator to reflect actual environmental conditions, not under over-simplified artificial network conditions. The proposed relocation protocol demonstrates a uniform and energy-efficient movement with ping-pong free capability.

16.
Front Bioeng Biotechnol ; 8: 548947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102453

RESUMO

We propose a novel wearable robotic glove or exo-glove design scalable to the variation of the hand kinematics. While most of the traditional robot hand is driven by rotating the joint directly with a rigid body, our exo-glove deforms a robotic finger's skin and, thus, the hand skeleton joints. Multiple tendons woven on the exo-glove's surface can make multi-DOF finger joint motions. We allocated tendons to mimic a hand's intrinsic and extrinsic muscles. Thus, a robotic hand actuated with the exo-glove can perform natural finger motions, including abduction/adduction and flexion/extension of finger joints. Moreover, additional tendons for the thumb enable power grips and the robotic hand's human-like motion. The proposed design approach places all the actuators on the surface without directly actuating any of the hand skeleton's joint. Therefore, a random hand skeleton can work as a robotic hand by putting the wearable robotic glove on it. Thus, the proposed model provides a high degree of freedom on choosing hand skeletons. We expect the aforementioned biomimetic features of our proposed method will benefit not only traditional robotic hands design but also the design of prosthetic hands and robot power-assisted hand glove.

17.
Inorg Chem ; 59(17): 12461-12470, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32852204

RESUMO

Rigid naphthalene benzimidazole (NBI) based ligands (L1 and L2) are synthesized and utilized to make deep red phosphorescent cyclometalated iridium(III) complexes ([Ir(NBI)2(PyPzCF3)] (1) and [Ir(DPANBI)2(PyPzCF3)] (2)). Complexes 1 and 2 are prepared from the reaction of L1/L2 with the aid of ancillary ligands (PyPzCF3, 2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridine) in a two step method. The complexes are characterized by analytical and spectroscopic methods, as well as X-ray diffraction for 1. These complexes show a strong emission in the range of 635-700 nm that extends up to the near-infrared region (800 nm). The introduction of the diphenylamino (DPA) donor group on the naphthalene unit leads to a further red-shift in the emission. The complexes exhibit radiative quantum efficiency (ΦPL) of 0.27-0.29 in poly(methylmethacrylate) film and relatively short phosphorescence decay lifetimes (τ = 1.1-3.5 µs). The structural, electronic, and optical properties are investigated with the support of density functional theory (DFT) and time-dependent-DFT calculations. The calculation results indicate that the lowest-lying triplet (T1) excited state of 1 has a mixed metal-to-ligand charge transfer (3MLCT) and ligand-centered (3LC) character, while 2 shows a dominant 3LC character. Deep red-emitting organic light-emitting diodes fabricated using 1 as a dopant display a maximum external quantum efficiency of 10.9% with the CIE color coordinates of (0.690, 0.294), with an emission centered at 644 and 700 nm. Similarly, the emitter 2 also shows a maximum external quantum efficiency of 6.9% with emissions at 657 and 722 nm.

18.
Oncol Lett ; 20(2): 1989-1998, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32724445

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is one of the most lethal childhood brain tumors. This tumor is unique because it is detected exclusively in the ventral pons of patients aged between 6 and 7 years, which suggests a developmental nature of its formation. Signal transducer and activator of transcription 3 (STAT3) is a critical molecule for the differentiation of neural stem cells into astrocytes during neurodevelopment. Additionally, STAT3 is associated with oncogenesis and the epithelial-mesenchymal transition (EMT) in various types of tumor. In recent years, several studies have demonstrated the oncogenic role of STAT3 in high-grade gliomas. However, the role of STAT3 in DIPG at the cellular level remains unknown. To assess the possible association between gliogenesis and DIPG, the expression levels of various molecules participating in the differentiation of neural stem cells were compared between normal brain control tissues and DIPG tissues using open public data. All of the screened genes exhibited significantly increased expression in DIPG tissues compared with normal tissues. As STAT3 expression was the most increased, the effect of STAT3 inhibition in a DIPG cell line was assessed via STAT3 short hairpin (sh)RNA transfection and treatment with AG490, a STAT3 inhibitor. Changes in viability, apoptosis, EMT and radiation therapy efficiency were also evaluated. Downregulation of STAT3 resulted in decreased cyclin D1 expression and cell viability, migration and invasion. Additionally, treatment with STAT3 shRNA or AG490 suppressed the EMT phenotype. Finally, when radiation was administered in combination with STAT3 inhibition, the therapeutic efficiency, assessed by cell viability and DNA damage repair, was increased. The present results suggest that STAT3 is a potential therapeutic target in DIPG, especially when combined with radiation therapy.

19.
Front Chem ; 8: 538, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714897

RESUMO

We report the impact of boron acceptors on the thermally activated delayed fluorescence (TADF) properties of ortho-donor-appended triarylboron compounds. Different boryl acceptor moieties, such as 9-boraanthryl (1), 10H-phenoxaboryl (2), and dimesitylboryl (BMes2, 3) groups have been introduced into an ortho donor (D)-acceptor (A) backbone structure containing a 9,9-diphenylacridine (DPAC) donor. X-ray crystal diffraction and NMR spectroscopy evidence the presence of steric congestion around the boron atom along with a highly twisted D-A structure. A short contact of 2.906 Šbetween the N and B atoms, which is indicative of an N → B nonbonding electronic interaction, is observed in the crystal structure of 2. All compounds are highly emissive (PLQYs = 90-99%) and display strong TADF properties in both solution and solid state. The fluorescence bands of cyclic boryl-containing 1 and 2 are substantially blue-shifted compared to that of BMes2-containing 3. In particular, the PL emission bandwidths of 1 and 2 are narrower than that of 3. High-efficiency TADF-OLEDs are realized using 1-3 as emitters. Among them, the devices based on the cyclic boryl emitters exhibit pure blue electroluminescence (EL) and narrower EL bands than the device with 3. Furthermore, the device fabricated with emitter 1 achieves a high external quantum efficiency of 25.8%.

20.
Sci Rep ; 10(1): 4042, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111941

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...