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We propose a magneto-optical diffractive deep neural network (MO-D2NN). We simulated several MO-D2NNs, each of which consists of five hidden layers made of a magnetic material that contains 100 × 100 magnetic domains with a domain width of 1 µm and an interlayer distance of 0.7 mm. The networks demonstrate a classification accuracy of > 90% for the MNIST dataset when light intensity is used as the classification measure. Moreover, an accuracy of > 80% is obtained even for a small Faraday rotation angle of π/100 rad when the angle of polarization is used as the classification measure. The MO-D2NN allows the hidden layers to be rewritten, which is not possible with previous implementations of D2NNs.
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We present a new type of aperture antenna with V-groove structures that are made of Au to enhance strong circularly polarized light (CPL). Simulations using the finite element method revealed that strong CPL was enhanced within the aperture with a diameter of 10 nm. The intensity of the electric field was enhanced and was 22,700 times greater than that of the incident light. The channel plasmon polaritons generated in the V-groove structures were responsible for the strong enhancement. The influence of the angle and length of the V-groove on the enhancement of the CPL was investigated.
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BACKGROUND: Melanoma is one of the deadliest skin cancers. The treatment of advanced melanoma has been dramatically improved by immune checkpoint inhibitors and targeted therapies. However, many patients still do not respond to these therapies. OBJECTIVE: To investigate whether NAP1L4 can be a new therapeutic target for melanoma. METHODS: Immunohistochemical analysis of human nevus and melanoma tissues was performed. Real-time RT-PCR and immunoblotting were performed using human samples and melanoma cell lines. Next, we examined the effect of NAP1L4 knockdown in melanoma cell lines using cell migration and invasion assays. To investigate the molecular mechanism related to these results, immunoblotting of p21 and Slug was examined. MMP-2 and MMP-9 activity assays were also performed. Further, pathway analysis between NAP1L4 and MMP-2 was performed. Finally, the effects of NAP1L4 knockdown on cell proliferation, apoptosis, and cell cycle were analyzed. RESULTS: NAP1L4 was overexpressed in melanoma tissues compared to the nevus tissue. NAP1L4 knockdown reduced melanoma cell migration and invasion. NAP1L4 knockdown upregulated p21 and downregulated Slug expression in melanoma cells. NAP1L4 knockdown decreased the active levels of MMP-2 in the supernatant from melanoma cells. NAP1L4 knockdown inhibited apoptosis in camptothecin-induced DNA damage, induced cell cycle arrest at the G1/S phase, and inhibited cell proliferation. CONCLUSIONS: NAP1L4 may play a role in cell migration and invasion in melanoma cells through the regulation of Slug. We propose that NAP1L4 can be a new therapeutic target for proliferation and invasion of melanoma cells.
Assuntos
Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma/genética , Proteínas Nucleares/metabolismo , Neoplasias Cutâneas/genética , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Técnicas de Silenciamento de Genes , Humanos , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Melanoma/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/prevenção & controle , Estadiamento de Neoplasias , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Fatores de Transcrição da Família Snail/genéticaRESUMO
An analytical method for the simultaneous quantitation of ten trichothecenes of type A (HT-2 toxin, T-2 toxin, diacetoxyscirpenol, and neosolaniol) and type B (3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, deoxynivalenol, deoxynivalenol-3-glucoside, nivalenol, and fusarenon-X) in feed has been developed using liquid chromatography with tandem mass spectrometry. Mycotoxins extracted twice from samples using aqueous acetonitrile were purified using a multifunctional clean-up column, followed by a phospholipid removal column. Trichothecenes were analysed using liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry. The extraction efficiency of the mycotoxins and the repeatability of some were improved by repeated extractions. Ionization enhancement (signal enhancement) of some mycotoxins was improved by using the phospholipid removal column at the clean-up step. Spike and recovery tests of trichothecenes were conducted on maize, barley, soybean meal, rapeseed meal, and formula feeds (for starting broiler chicks, suckling pigs, and beef cattle). The mean recovery values were 70.6-119% with relative standard deviations < 17%. The limit of quantification and the limit of detection of our method were 20 and 6 µg/kg, respectively, for 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol; 10 and 3 µg/kg, respectively, for T-2 toxin, deoxynivalenol, and fusarenon-X; and 5 and 2 µg/kg, respectively, for nivalenol and the remaining mycotoxins.
Assuntos
Ração Animal/análise , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análise , Espectrometria de Massas em Tandem/métodos , Tricotecenos/análise , Animais , Glucosídeos/análise , Limite de Detecção , Suínos , Tricotecenos/classificaçãoRESUMO
Methyl-CpG binding domain protein 3 (MBD3) belongs to the methyl-CpG binding protein family. MBD3 facilitates the initiation of neural stem cell reprogramming. Melanoma originates in melanocytes derived from neural crest stem cells; therefore, we investigated the role of MBD3 in melanoma. MBD3 was overexpressed in melanoma compared with pigmented nevi. MBD3 knockdown had no effect on the proliferation of melanoma cells (A375 and A2058 cells). Contrarily, it significantly reduced the migration and invasion of A375 cells, but had no significant effect on A2058 cells. Furthermore, MBD3 knockdown reduced N-cadherin protein levels and matrix metalloproteinase-2 (MMP-2) activity in A375 cells, but had no significant effect on A2058 cells. Based on these results, the MBD3 expression level may be a useful biomarker for the diagnosis of melanoma. Thus, MBD3 has potential as a novel therapeutic target for some melanoma patients.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Epigênese Genética/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Nevo Pigmentado/tratamento farmacológico , Nevo Pigmentado/patologia , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: A previous study revealed that matrin-3 is an essential component in maintaining fibroblast growth factor 2 (FGF2)-mediated undifferentiation of neural stem cells (NSCs) using a proteomics approach. Malignant melanoma (MM) arises from melanocytes that originate from neural crest stem cells during development. Additionally, it has been reported that the expression of FGF2 is positively correlated with the progression of MM. OBJECTIVE: We expected that matrin-3, as a downstream component of FGF2, might be associated with the aggressiveness or differentiation of MM. METHODS: Matrin-3 expression was measured in human melanoma patient tissues and human MM cell lines. We analyzed the effect of matrin-3 siRNA on the proliferation of human MM cell lines and focused on cell cycle progression and apoptosis. We carried out in vivo xenograft tumor experiments by implanting A375 cells transfected with matrin-3 shRNA. RESULTS: Matrin-3 was highly expressed in MM, and matrin-3 knockdown inhibited the proliferation of melanoma cellsin vivo and in vitro. Furthermore, we found that matrin-3 knockdown led to an accumulation of cells in the G1 phase and an increase in apoptotic cell number. CONCLUSION: Our results suggest that matrin-3 could be a new therapeutic target for the treatment of MM.
Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Nevo/genética , Proteínas Associadas à Matriz Nuclear/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/genética , Biópsia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Criança , Pré-Escolar , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Pessoa de Meia-Idade , Nevo/patologia , Proteínas Associadas à Matriz Nuclear/antagonistas & inibidores , Proteínas Associadas à Matriz Nuclear/genética , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto JovemRESUMO
Unlike ferromagnetic materials, ferrimagnetic metals have recently received considerable attention due to their bulk perpendicular magnetic anisotropy, low net magnetization and tunable magnetic properties. This makes them perfect candidates for the research of recently discovered spin-torque related phenomena. Among other ferrimagnetic metals, GdFe has an advantage in relatively large magnetic moments in both sublattices and tunability of compensation point above the room temperature by small changes in its composition. We present a systematic study of optical and magneto-optical properties of amorphous GdxFe(100-x) thin films of various compositions (x = 18.3, 20.0, 24.7, 26.7) prepared by DC sputtering on thermally oxidized SiO2 substrates. A combination of spectroscopic ellipsometry and magneto-optical spectroscopy in the photon energy range from 1.5 to 5.5 eV with advanced theoretical models allowed us to deduce the spectral dependence of complete permittivity tensors across the compensation point. Such information is important for further optical detection of spin related phenomena driven by vicinity of compensation point in nanostructures containing GdFe.
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Sterigmatocystin (STC) and aflatoxin B1 (AFB1) were analyzed in 246 corn samples, 126 soybean meal samples, and 861 formula feed samples from the Japanese market between April 2010 and March 2015. The detection rate, the highest concentration, and the mean concentration of STC were respectively 14%, 6.4 µg/kg, and 1.2 µg/kg for corn; 14%, 1.1 µg/kg, and 0.63 µg/kg for soybean meal; and 43%, 9.1 µg/kg, and 0.97 µg/kg for formula feed. The detection rate, the highest concentration, and the mean concentration of AFB1 were respectively 46%, 24 µg/kg, and 3.9 µg/kg for corn; 30%, 6.7 µg/kg, and 1.1 µg/kg for soybean meal; and 47%, 20 µg/kg, and 1.6 µg/kg for formula feed. A weak negative correlation between the STC and AFB1 concentrations was observed: there was a high concentration of AFB1 in samples that contained a lower concentration of STC and vice versa. Spearman's rank correlation coefficient showed a weak negative correlation of - 0.30 (p < 0.001, n = 128) for corn and - 0.23 (p < 0.001, n = 575) for formula feed. In conclusion, no correlation was observed between the mean concentrations of STC contamination in formula feed (0.97 µg/kg) and in corn (1.2 µg/kg) and the blending rate (approximately 50%). The rate of STC contamination in the formula feed (43%) was higher than that in corn (14%). Therefore, it is likely that ingredients other than corn contribute to the contamination of formula feed with STC. In this study, regarding STC, problematic samples were not found.
Assuntos
Aflatoxina B1/análise , Análise de Alimentos , Glycine max , Venenos/análise , Esterigmatocistina/análise , Zea mays , JapãoRESUMO
A lot of diseases occur on the skin of elderly persons. We report four elderly cases of bullous dermatosis that did not meet various differential diagnoses. Japanese, heart failure, atrophic skin and leg edema probably due to aging, as well as flaccid or tense bullae localized in legs were the common factors to our patients. Such conditions may be increased in coming aging society. Accordingly, it is worth regarding such symptom as the new clinical entity, which may comfort patients with similar condition and attract further attention.
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Dermatoses da Perna/diagnóstico , Dermatopatias Vesiculobolhosas/diagnóstico , Fatores Etários , Idoso de 80 Anos ou mais , Anti-Infecciosos Locais/uso terapêutico , Diagnóstico Diferencial , Etacridina/uso terapêutico , Feminino , Insuficiência Cardíaca/complicações , Humanos , Mordeduras e Picadas de Insetos/diagnóstico , Dermatoses da Perna/complicações , Dermatoses da Perna/patologia , Dermatoses da Perna/terapia , Masculino , Penfigoide Bolhoso/diagnóstico , Pênfigo/diagnóstico , Dermatopatias Vesiculobolhosas/complicações , Dermatopatias Vesiculobolhosas/patologia , Dermatopatias Vesiculobolhosas/terapia , Meias de CompressãoRESUMO
Optical and magneto-optical properties of amorphous Gd22Fe78 (GdFe) thin films prepared by direct current (DC) sputtering on thermally oxidized substrates were characterized by the combination of spectroscopic ellipsometry and magneto-optical spectroscopy in the photon energy range from 1.5 to 5.5 eV. Thin SiNx and Ru coatings were used to prevent the GdFe surface oxidation and contamination. Using advanced theoretical models spectral dependence of the complete permittivity tensor and spectral dependence of the absorption coefficient were deduced from experimental data. No significant changes in the optical properties upon different coatings were observed, indicating reliability of used analysis.
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Imunoterapia/métodos , Melanoma/terapia , Células Mieloides/transplante , Neoplasias Cutâneas/terapia , Animais , Diferenciação Celular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Interferon beta/genética , Interferon beta/imunologia , Interferon beta/metabolismo , Interleucina-15/genética , Interleucina-15/imunologia , Interleucina-15/metabolismo , Melanoma/imunologia , Melanoma/patologia , Camundongos , Células Mieloides/imunologia , Células Mieloides/metabolismo , Receptores de Interleucina-15/genética , Receptores de Interleucina-15/imunologia , Receptores de Interleucina-15/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Evasão Tumoral/imunologiaRESUMO
Polarization properties of apertureless-type scanning near-field optical microscopy (a-SNOM) were measured experimentally and were also analyzed using a finite-difference time-domain (FDTD) simulation. Our study reveals that the polarization properties in the a-SNOM are maintained and the a-SNOM works as a wave plate expressed by a Jones matrix. The measured signals obtained by the lock-in detection technique could be decomposed into signals scattered from near-field region and background signals reflected by tip and sample. Polarization images measured by a-SNOM with an angle resolution of 1° are shown. FDTD analysis also reveals the polarization properties of light in the area between a tip and a sample are p-polarization in most of cases.
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Insulin secretion by pancreatic islets is a multicellular process. In addition to other essential systems, gap junctions are an important component of cell-to-cell communication in pancreatic islets. It is well known that dysfunction of gap junctions causes inappropriate insulin secretion. The anti-ulcer agent, irsogladine, increases gap junctions in some cell types. To examine the effect of irsogladine on insulin secretion, we investigated insulin secretion by MIN6 cells treated with or without irsogladine. The expression of connexin 36 proteins and intracellular cAMP levels were also determined using immunoblotting and ELISA assays, respectively. Irsogladine had no effect on insulin secretion under 5.6mM glucose conditions. However, under 16.7 mM glucose conditions, irsogladine (1.0 × 10(-5)M) induced a 1.7 ± 0.20 fold increase in insulin secretion compared to the control (P<0.05). This effect of irsogladine on insulin secretion was inhibited by the addition of the gap junction inhibitor 18-beta-glycyrrhetinic acid. Irsogladine treatment increased the protein level of connexin 36 in the plasma membrane fraction. The intracellular cAMP level in MIN6 cells was significantly, but mildly, increased by irsogladine treatment. Furthermore, Rp-cAMP and H89 inhibited the effects of irsogladine on insulin secretion under high glucose conditions. Irsogladine increases insulin secretion under high glucose conditions. The up-regulation of gap junction channels and the increased level of intracellular cAMP induced by irsogladine treatment suggest that these phenomena are involved in irsogladine-induced increased insulin secretion.
Assuntos
Antiulcerosos/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Triazinas/farmacologia , Animais , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Conexinas/metabolismo , AMP Cíclico/metabolismo , Ensaio de Imunoadsorção Enzimática , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Secreção de Insulina , Camundongos , Regulação para Cima/efeitos dos fármacos , Proteína delta-2 de Junções ComunicantesRESUMO
Aquaporin-1 (AQP1), a water channel protein, has been shown to play an important role in tumor growth and angiogenesis in mouse endothelial cells. We recently reported that the expression of AQP1 mRNA was induced in cultured human retinal vascular endothelial cells (HRVECs) under hypoxia. In the present study, HRVECs were cultured under normoxia or hypoxia (1% O(2)) to elucidate the mechanism of hypoxic induction of AQP1. AQP1 mRNA expression was increased 1.7 ± 0.24-fold under hypoxia compared with that under normoxia (p < 0.01). This increase was almost completely blocked by the transcriptional inhibitor actinomycin D (p < 0.01). The degradation of AQP1 mRNA showed no difference under normoxia or hypoxia. These data suggest that the hypoxia-induced expression of AQP1 results from RNA transcription. The sequence located from -1338 to -1334 bp is identical to the consensus sequence of the hypoxia-inducible factor 1 (HIF-1) binding site. The promoter activities of the two constructs including this putative HIF-1 binding site showed 2.0 ± 0.67-fold increase and 2.9 ± 1.9-fold increase under hypoxia when compared with those under normoxia. However, both deletion and mutation of the HIF-1 binding site abrogated this effect. These data suggest that this sequence mediates the transcriptional activation of AQP1 by hypoxia. The chromatin immunoprecipitation assay showed that HIF-1α bound to the putative HIF-1 binding site. In conclusion, hypoxia-induced expression of AQP1 requires transcriptional activation, and the HIF-1 binding site of the 5'-promoter is necessary for transcriptional activation in HRVECs.
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Aquaporina 1/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ativação Transcricional , Sítios de Ligação , Hipóxia Celular/genética , Dactinomicina/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
Reactions of the head-to-head 2-pyridonato-bridged cis-diammineplatinum(III) dinuclear complex having nonequivalent two platinum atoms, Pt(N(2)O(2)) and Pt(N(4)), with p-styrenesulfonate, 2-methyl-2-propene-1-sulfonate, 4-penten-1-ol, and 4-pentyn-1-ol were studied kinetically. Under the pseudo first-order reaction conditions that the concentration of the Pt(III) dinuclear complex is much smaller than that of olefin, a consecutive basically four-step reaction was observed: the olefin pi-coordinates preferentially to the Pt(N(2)O(2)) in the first step (step 1), followed by the second pi-coordination of another olefin molecule to the Pt(N(4)) (step 2). In the next step (step 3), the nucleophilic attack of water to the coordinated olefin triggers the pi-sigma bond conversion on the Pt(N(2)O(2)), and the second pi-bonding olefin molecule on the Pt(N(4)) is released. Finally, reductive elimination occurs to the alkyl group on the Pt(N(2)O(2)) to produce the alkyl compound (step 4). The first water substitution with olefin (step 1) occurs to the diaqua and aquahydroxo forms of the complex, whereas the second substitution (step 2) proceeds either on the coordinated OH(-) on the Pt(N(4)) (path a) or on the coordinatively unsaturated five-coordinate intermediate of the Pt(N(4)) (path b), in addition to the common substitution of H(2)O (path c). The reactions of p-styrenesulfonate and 2-methyl-2-propene-1-sulfonate proceed through paths b and c, whereas the reactions of 4-penten-1-ol and 4-pentyn-1-ol proceed through paths a and c. This difference reflects the difference of the trans effect and/or trans influence of the pi-coordinated olefins on the Pt(N(2)O(2)). The pentacoordinate state in path b is employed only by the sulfo-olefins, because these exert stronger trans effect. The steps 3 and 4 reflect the effect of the axial alkyl ligand (R) on the charge localization (R-Pt(IV)(N(2)O(2))-Pt(II)(N(4))) and delocalization (R-Pt(III)(N(2)O(2))-Pt(III)(N(4))-OH(2)); when R is p-styrenesulfonate having an electron withdrawing group, the charge localization in the dimer is less pronounced and the water molecule on the Pt(N(4)) atom is retained (R-Pt(III)(N(2)O(2))-Pt(III)(N(4))-OH(2)) in the intermediate state. In both routes, the alkyl group undergoes nucleophilic attack of water, and the oxidized products are released via reductive elimination.