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OBJECTIVES: Glioblastoma (GBM) is the most aggressive of intracranial gliomas. Despite the maximal treatment intervention, the median survival rate is still about 14-16 months. Nuclear receptor-binding protein 1 (NRBP1) has a potential growth-promoting role on biology function of cells. In this study, we investigated whether NRBP1 promotes GBM malignant phenotypes and the potential mechanisms. METHODS: The correlation between NRBP1 and glioma grade, prognosis in TCGA/CGGA databases and our clinical data were analyzed. Next, we conducted knockout and overexpression of NRBP1 on GBM cells to verify that NRBP1 promoted cell proliferation, invasion, and migration in vitro and in vivo. Finally, we detected the impact of NRBP1 on PI3K/Akt signaling pathway and EMT. RESULTS: There was a correlation between elevated NRBP1 expression and advanced stage glioma, as well as decreased overall and disease-free survival. The suppression of proliferation, invasion, and migration of tumor cells was observed upon NRBP1 knockout, and in vitro studies also demonstrated the induction of apoptotic cell death. Whereas, its overexpression is associated with high multiplication rate, migration, invasion, and apoptotic escape. GO enrichment and KEGG analysis revealed that NRBP1 regulated differentially expressed gene clusters are involved in PI3K/Akt signaling pathway, as well as EMT mediated by this pathway. Moreover, the effects of NRBP1 knockdown and overexpression on GBM were mitigated by MK-2206 and SC79, both of which respectively function as an inhibitor and an activator of the PI3K/Akt signaling pathway. Similarly, the suppression of NRBP1 led to a decrease in tumor growth, whereas its overexpression promoted tumor growth in a mouse model. CONCLUSIONS: This study shows that NRBP1 promotes malignant phenotypes in GBM by activating PI3K/Akt pathway. Hence, it can function as both a predictive indicator and a new target for therapies in GBM treatment.
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Neoplasias Encefálicas , Movimiento Celular , Proliferación Celular , Glioblastoma , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Apoptosis , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/metabolismo , Ratones Desnudos , Fenotipo , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Central nervous system tumor with BCOR internal tandem duplication (CNS tumor with BCOR-ITD) constitutes a molecularly distinct entity, characterized by internal tandem duplication within exon 15 of the BCOR transcriptional co-repressor gene (BCOR-ITD). The current study aimed to elucidate the clinical, pathological, and molecular attributes of CNS tumors with BCOR-ITD and explore their putative cellular origin. This study cohort comprised four pediatric cases, aged 23 months to 13 years at initial presentation. Magnetic resonance imaging revealed large, well-circumscribed intra-CNS masses localized heterogeneously throughout the CNS. Microscopically, tumors were composed of spindle to ovoid cells, exhibiting perivascular pseudorosettes and palisading necrosis, but lacking microvascular proliferation. Immunohistochemical staining showed diffuse tumor cell expression of BCOR, CD56, CD99, vimentin, and the stem cell markers PAX6, SOX2, CD133 and Nestin, alongside focal positivity for Olig-2, S100, SOX10, Syn and NeuN. Molecularly, all cases harbored BCOR-ITDs ranging from 87 to 119 base pairs in length, including one case with two distinct ITDs. Notably, the ITDs were interrupted by unique 1-3â¯bp insertions in all cases. In summary, CNS tumors with BCOR-ITD exhibit characteristic clinical, pathological, and molecular features detectable through BCOR immunohistochemistry and confirmatory molecular analyses. Their expression of stem cell markers raises the possibility of an origin from neuroepithelial stem cells rather than representing true embryonal neoplasms.
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Neoplasias del Sistema Nervioso Central , Proteínas Proto-Oncogénicas , Proteínas Represoras , Humanos , Proteínas Represoras/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/metabolismo , Niño , Adolescente , Masculino , Femenino , Lactante , Preescolar , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Secuencias Repetidas en Tándem , Duplicación de GenRESUMEN
Strong exciton-plasmon interactions between layered two-dimensional (2D) semiconductors and gap plasmons show a great potential to implement cavity quantum electrodynamics under ambient conditions. However, achieving a robust plasmon-exciton coupling with nanocavities is still very challenging, because the layer area is usually small in the conventional approaches. Here, we report on a robust strong exciton-plasmon coupling between the gap mode of a bowtie and the excitons in MoS2 layers with gold-assisted mechanical exfoliation and nondestructive wet transfer techniques for a large-area layer. Due to the ultrasmall mode volume and strong in-plane field, the estimated effective exciton number contributing to the coupling is largely reduced. With a corrected exciton transition dipole moment, the exciton numbers are extracted as being 40 for the case of a single layer and 48 for eight layers. Our work paves the way to realize strong coupling with 2D materials with a small number of excitons at room temperature.
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We report on controllable cavity modes by controlling the backscattering by two identical scatterers. Periodic changes of the backscattering coupling between two degenerate cavity modes are observed with the changing angle between two scatterers and elucidated by a theoretical model using two-mode approximation and numerical simulations. The periodically appearing single-peak cavity modes indicate mode degeneracy at diabolical points. Interactions between single quantum dots and cavity modes are then investigated. Enhanced emission of a quantum dot with a six-fold intensity increase is obtained in a microdisk at a diabolical point. This method to control cavity modes allows large-scale integration, high reproducibility and flexible design of the size, the location, the quantity and the shape for scatterers, which can be applied for integrated photonic structures with scatterer-modified light-matter interaction.
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Two-dimensional (2D) layered hybrid perovskites provide an ideal platform for studying the properties of excitons. Here, we report on a strong triplet-exciton and longitudinal-optical (LO) phonon coupling in 2D (C6H5CH2CH2NH3, PEA)2PbBr4 perovskites. The triplet excitons exhibit strong photoluminescence (PL) in thick perovskite microflakes, and the PL is not detectable for monolayer microflakes. The coupling strength of the triplet exciton-LO phonon is approximately two to three times greater than that of the singlet exciton-LO phonon with a LO phonon energy of about 21 meV. This difference might due to the different locations of singlet excitons located in the well and triplet excitons located in the barrier in the 2D layered perovskite. Revealing the strong coupling of triplet exciton-LO phonon provides a fundamental understanding of many-body interaction in hybrid perovskites, which is useful to develop and optimize the optoelectronic devices based on 2D perovskites in the future.
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In single microdisks, embedded active emitters intrinsically affect the cavity modes of the microdisks, resulting in trivial symmetric backscattering and low controllability. Here we demonstrate macroscopic control of the backscattering direction by optimizing the cavity size. The signature of the positive and negative backscattering directions in each single microdisk is confirmed with two strongly coupled microdisks. Furthermore, diabolical points are achieved at the resonance of the two microdisks, which agrees well with theoretical calculations considering the backscattering directions. Diabolical points in active optical structures pave the way for an implementation of quantum information processing with geometric phase in quantum photonic networks.
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Large coupling strengths in exciton-photon interactions are important for the quantum photonic network, while strong cavity-quantum dot interactions have been focused on s-shell excitons with small coupling strengths. Here we demonstrate strong interactions between cavities and p-shell excitons with a great enhancement by the in situ wave-function control. The p-shell excitons are demonstrated with much larger wave-function extents and nonlocal interactions beyond the dipole approximation. Then the interaction is tuned from the nonlocal to the local regime by the wave function shrinking, during which the enhancement is obtained. A large coupling strength of 210 µeV has been achieved, indicating the great potential of p-shell excitons for coherent information exchange. Furthermore, we propose a distributed delay model to quantitatively explain the coupling strength variation, revealing the intertwining of excitons and photons beyond the dipole approximation.
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Undifferentiated sinonasal malignant melanoma (MM) is a rare type of tumor, which can be easily misdiagnosed. The present study reports a 41-year-old male patient who presented with a 4-day history of epistaxis. Clinical examination and radiological imaging lead to the detection of a mass in the right sinonasal region. Histopathological examination revealed that the mass was composed of malignant epithelioid cells arranged in nests and sheets. These cells displayed a hemangiopericytoma-like pattern with antler-like branching vessels. Immunohistochemical staining revealed that the tumor cells exhibited negative expression of melanocytic markers. This increased the difficulty of distinguishing undifferentiated MM from other malignant tumors located in the sinonasal area, particularly undifferentiated nasopharyngeal carcinoma. The diagnosis of undifferentiated MM was determined by ultrastructures, including the mature melanosomes and premelanosomes, in tumor cells by transmission electron microscopy. The present study suggests that the analysis of cancer stem cell marker and vasculogenic mimicry may be an important auxiliary tool for the diagnosis of MM.
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Defects are detrimental for optoelectronics devices, such as stacking faults can form carrier-transportation barriers, and foreign impurities (Au) with deep-energy levels can form carrier traps and nonradiative recombination centers. Here, self-catalyzed p-type GaAs nanowires (NWs) with a pure zinc blende (ZB) structure are first developed, and then a photodetector made from these NWs is fabricated. Due to the absence of stacking faults and suppression of large amount of defects with deep energy levels, the photodetector exhibits room-temperature high photoresponsivity of 1.45 × 105 A W-1 and excellent specific detectivity (D*) up to 1.48 × 1014 Jones for a low-intensity light signal of wavelength 632.8 nm, which outperforms previously reported NW-based photodetectors. These results demonstrate these self-catalyzed pure-ZB GaAs NWs to be promising candidates for optoelectronics applications.