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AIMS: Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process. METHODS: As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients' blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs. RESULTS: A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients' neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model. CONCLUSIONS: NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS. Video Abstract.
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Lesões Encefálicas , Armadilhas Extracelulares , Proteína HMGB1 , AVC Isquêmico , Trombose , Animais , Camundongos , Humanos , Armadilhas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Trombose/metabolismo , Neutrófilos , Lesões Encefálicas/metabolismoRESUMO
A quaternary metal thioarsenate infrared (IR) nonlinear optical (NLO) compound Na4SrAs2S8 was successfully prepared by a high-temperature reaction method from stoichiometric agents. It crystallizes in the tetragonal P4n2 with the unit cell parameters a = 10.0393(3) Å, c = 6.9638(3) Å, and Z = 2, with the basic structural groups of isolated AsS4 tetrahedra. Compared with benchmark IR NLO crystal AgGaS2 (AGS), the title compound exhibits balanced optical properties of large band gap (3.05 eV vs. 2.60 eV) and considerable second harmonic generation response (0.95 × AGS). Moreover, the combined powder X-ray diffraction and differential scanning calorimetry analyses demonstrate that Na4SrAs2S8 is a congruent-melting compound with a low melting point of 668 °C, which is benefical for bulk single crystal growth. Experimental and theoretical calculation results indicate that Na4SrAs2S8 is a practically usable IR NLO crystal, also motivating the exploration of thioarsenates as high-performance IR NLO candidates.
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Microencapsulated enzymes have been found to effectively accelerate cheese ripening. However, microencapsulated enzyme release is difficult to control, often resulting in enzyme release during cheese processing and causing texture and flavor defects. This study aims to address this issue by developing aminopeptidase-loaded pH-responsive chitosan microspheres (A-CM) for precise enzyme release during cheese ripening. An aminopeptidase with an isoelectric point (pH 5.4) close to the pH value of cheese ripening was loaded on chitosan microspheres through electrostatic interaction. Turbidity titration measurements revealed that pH 6.5 was optimal for binding aminopeptidase and microspheres, affording the highest loading efficiency of 58.16%. Various characterization techniques, including scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy confirmed the successful loading of aminopeptidase molecules on the chitosan microspheres. In vitro release experiments conducted during simulated cheese production demonstrated that aminopeptidase release from A-CM was pH responsive. The microspheres retained the enzyme during the coagulation and cheddaring processes (pH 5.5-6.5) and only released it after entering the cheese-ripening stage (pH 5.0-5.5). By loading aminopeptidase on chitosan microspheres, the loss rate of the enzyme in cheese whey was reduced by approximately 79%. Furthermore, compared with cheese without aminopeptidase and cheese with aminopeptidase added directly, the cheeses made with A-CM exhibited the highest proteolysis level and received superior sensory ratings for taste and smell. The content of key aroma substances, such as 2/3-methylbutanal and ethyl butyrate, in cheese with A-CM was more than 15 times higher than the others. This study provides an approach for accelerating cheese ripening through the use of microencapsulated enzymes.
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Aminopeptidases , Queijo , Quitosana , Microesferas , Quitosana/química , Concentração de Íons de Hidrogênio , Aminopeptidases/metabolismo , Animais , Manipulação de AlimentosRESUMO
Products of lipolysis released during digestion positively affect the metabolism of newborns. In contrast to the 3-layer biological membranes covering human milk (HM) fat, the lipid droplets in infant milk formula (IMF) are covered by a single membrane composed of casein and whey proteins. To reduce the differences in lipid structure between IMF and HM, studies have used milk fat globule membrane (MFGM) components such as milk polar lipids (MPL) to prepare emulsions mimicking HM fat globules However, few studies have elucidated the effect of membrane proteins (MP) on lipid digestion in infants. In this study, 3 kinds of emulsions were prepared: One with MPL as the interfaced of lipid droplets (RE-1), one with membrane protein concentrate (MPC) (RE-2) as the interface of lipid droplets, and one with both MPL and MPC (1:2) as the co-interface of lipid droplets (RE-3). The interfacial coverage of the emulsions was confirmed by measuring the contents of MPL and MPC at the lipid droplet interface, and by confocal laser scanning microscopy analyzed. By controlling the homogenization intensity, the specific surface area of lipid droplets was controlled at the same level among the 3 emulsions. The stability constants of the emulsions varied, and RE-1 was the most stable. During simulated in vitro infant gastrointestinal digestion, the amount of free fatty acids (FFA) released from the lipid droplets was significantly higher from those with MPC at the interface (RE-2, RE-3) than from that with MPL at the interface (RE-1). The amount of FFA released at the end of intestinal digestion of RE-1, RE-2, and RE-3 was 255.00 ± 3.54 µmol,328.75 ± 5.30 µmol, 298.50 ± 9.19 µmol, respectively. Compared with the lipid droplets in RE-2, those with MPL at the interface (RE-1, RE-3) released more unsaturated fatty acids (USFAs) during digestion. The emulsifying activity index was highest in RE-3 (MPL and MPC co-interface). The presence of MPL at the emulsion interface increased the release of USFAs, while the presence of MPC increased the release of FFA. These results show that both MPL and MP are indispensable in the construction of MFGM. Understanding their effects on digestion can provide new strategies for the development of infant foods.
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Aromatic aldehydes are widely used for the construction of covalent organic frameworks (COFs). However, due to the high flexibility, high steric hindrance, and low reactivity, it remains challenging to synthesize COFs using ketones as building units, especially the highly flexible aliphatic ones. Here, the single nickel site coordination strategy is reported to lock the configurations of the highly flexible diketimine to transform discrete oligomers or amorphous polymers into highly crystalline nickel-diketimine-linked COFs (named as Ni-DKI-COFs). The strategy has been successfully extended to the synthesis of a series of Ni-DKI-COFs by the condensation of three flexible diketones with two tridentate amines. Thanks to the ABC stacking model with high amount and easily accessible single nickel (II) sites on their 1D channels, Ni-DKI-COFs are exploited as well-defined electrocatalyst platforms for efficiently electro-upgrading biomass-derived 5-Hydroxymethylfurfural (HMF) into value-added 2,5-furandicarboxylic acid (FDCA) with a 99.9% yield and a 99.5% faradaic efficiency as well as a high turnover frequency of 0.31 s-1 .
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The majority of bioactive substances in the human diet come from polyphenols. Here, we use spectroscopy, molecular docking, molecular dynamics simulations, and in vitro digestion to look at the relationship between caffeine (CAF) and bovine lactoferrin (BLF). The correlation analysis of the CAF-BLF fluorescence quenching process revealed that the reaction was spontaneous and that the CAF-BLF fluorescence quenching process may have been static. The predominant intrinsic binding forces were hydrogen bonds and van der Waals forces, which were also supported by molecular docking and molecular dynamics simulations. Through Fourier infrared and circular dichroism spectroscopy experiments, it was found that CAF changed the secondary structure of BLF and might bind to the hydrophobic amino acids of BLF. Compared with BLF, CAF-BLF showed inhibitory effects on digestion in simulated in vitro digestion. It will be helpful to better understand the interaction between CAF and BLF and provide the basis for the development of innovative dairy products.
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Cafeína , Lactoferrina , Cafeína/química , Cafeína/metabolismo , Lactoferrina/química , Lactoferrina/metabolismo , Simulação de Acoplamento Molecular , Bovinos , Técnicas In Vitro , Digestão , Animais , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Dicroísmo Circular , Simulação de Dinâmica Molecular , LaticíniosRESUMO
With current trends to progressively miniaturize optical systems, it is now essential to look for alternative methods to control light at extremely small dimensions. Metalenses are composed of subwavelength nanostructures and have an excellent ability to manipulate the polarization, phase, and amplitude of incident light. Although great progress of metalenses has been made, the compact metalens-integrated devices have not been researched adequately. In the study, we present compact imaging devices for near-infrared microscopy, in which a metalens is exploited. The indicators including resolution, magnification, and image quality are investigated via imaging several specimens of intestinal cells to verify the overall performance of the imaging system. The further compact devices, where the metalens is integrated directly on the CMOS imaging sensor, are also researched to detect biomedical issues. This study provides an approach to constructing compact imaging devices based on metalenses for near-infrared microscopy, micro-telecopy, etc., which can promote the miniaturization tending of futural optical systems.
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PURPOSE: To characterize peripapillary intrachoroidal cavitation (PICC) in highly myopic participants and its associated risk factors. METHODS: This observational, cross-sectional study recruited 890 Chinese participants with bilateral high myopia, defined as ≤-6.00 diopters spherical power. Fundus photography and spectral-domain optical coherence tomography were used to determine the presence of PICC, defined as a yellow-orange lesion adjacent to the disc border with a corresponding intrachoroidal hyporeflective space. RESULTS: Among 890 participants, 884 right eyes were included for analysis. The rate of PICC was 3.6% (32 eyes). Peripapillary intrachoroidal cavitation was observed in two eyes without myopic retinal lesions, nine eyes with tessellated fundus only, 16 eyes with diffuse chorioretinal atrophy, and five eyes with patchy chorioretinal atrophy. The most commonly affected area was inferior disc border (87.5%), followed by multiple (9.4%) and superior (3.1%) disc borders. The multiple linear logistic regression model showed that older age, more myopic spherical equivalent, and longer axial length were associated with the presence of PICC. CONCLUSION: Peripapillary intrachoroidal cavitation was present in 3.6% of highly myopic eyes. It was more common in eyes with a higher myopic maculopathy category. Older age, more myopic spherical equivalent, and longer axial length were risk factors for the presence of PICC.
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Doenças da Coroide/diagnóstico , Angiofluoresceinografia/métodos , Miopia Degenerativa/complicações , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Doenças da Coroide/epidemiologia , Doenças da Coroide/etiologia , Estudos Transversais , Feminino , Seguimentos , Fundo de Olho , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/fisiopatologia , Estudos Prospectivos , Refração Ocular/fisiologia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: This article focuses on the roles and mechanism of lncRNA CRNDE on the progression of HCC. METHODS: We used qRT-PCR to detect the expression of lncRNA CRNDE in HCC cells, normal cells and clinical tissues. MTT assay, FCM analysis, Transwell migration and invasion assay were used to detect the effects of lncRNA CRNDE on cell viability, apoptosis, migration and invasion of HCC cells. The expression of apoptosis-related proteins Bcl-2, Bax, Cleaved Caspase 3, Cleaved Caspase 9, EMT epithelial marker E-cadherin and mesothelial marker Vimentin were analyzed by Western blot. Online prediction software was used to predict the binding sites between lncRNA CRNDE and miR-539-5p, or miR-539-5p and POU2F1 3'UTR. Dual luciferase reporter assay, qRT-PCR and RNA pulldown were used to detect target-relationship between lncRNA CRNDE and miR-539-5p. Dual luciferase reporter assay, qRT-PCR, Western blot and Immunofluorescence were used to detect target-relationship between miR-539-5p and POU2F1. qRT-PCR was used to detect the expression of miR-539-5p and POU2F1 in clinical tissues. Rescue experiments was used to evaluate the association among lncRNA CRNDE, miR-539-5p and POU2F1. Finally, we used Western blot to detect the effects of lncRNA CRNDE, miR-539-5p and POU2F1 on NF-κB and AKT pathway. RESULTS: lncRNA CRNDE was highly expressed in HCC cells and HCC tissues compared with normal cells and the corresponding adjacent normal tissues. lncRNA CRNDE promoted the cell viability, migration and invasion of HCC cells, while inhibited the apoptosis and promoted the EMT process of HCC cells. lncRNA CRNDE adsorbed miR-539-5p acts as a competitive endogenous RNA to regulate POU2F1 expression indirectly. In HCC clinical tissues, miR-539-5p expression decreased and POU2F1 increased compared with the corresponding adjacent normal tissues. lncRNA CRNDE/miR-539-5p/POU2-F1 participated the NF-κB and AKT pathway in HCC. CONCLUSION: lncRNA CRNDE promotes the expression of POU2F1 by adsorbing miR-539-5p, thus promoting the progression of HCC.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/secundário , MicroRNAs/genética , Fator 1 de Transcrição de Octâmero/metabolismo , RNA Longo não Codificante/genética , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To explore the associations between diffuse chorioretinal atrophy (DCA) and age, sex, axial length, spherical equivalent, and best-corrected visual acuity (BCVA) among highly myopic eyes. METHODS: This study included right eyes of 857 bilaterally highly myopic individuals from the ZOC-BHVI Cohort Study. Participants underwent examinations, including BCVA, ocular biometry, autorefraction, and color fundus photography. An Early Treatment Diabetic Retinopathy Study grid was applied on the fundus photographs to evaluate the location of DCA, which was graded into four categories (D0-D3). The characteristics and ocular biometry were compared between participants' eyes with and without DCA. RESULTS: Diffuse chorioretinal atrophy was found in 177 (20.6%) eyes. The proportion of participants with DCA in age groups of 7 to 11, 12 to 18, 19 to 39, and ≥ 40 years old was 20.9%, 9.2%, 23.1%, and 52.9%, respectively. The proportion of DCA significantly increased with longer axial length and worse myopic spherical equivalent. Eyes with DCA had poorer BCVA (Snellen visual acuity 20/36, logarithm of minimal angle of resolution 0.26 ± 0.25) than those without DCA (Snellen visual acuity 20/23, logarithm of minimal angle of resolution 0.06 ± 0.14) (P < 0.001). The BCVA gradually declined as the lesion got closer to the fovea (P for trend < 0.001). CONCLUSION: The proportion of DCA increased with older age, longer axial length, and more myopic spherical equivalent. Diffuse chorioretinal atrophy is a vision-threatening complication of high myopia where BCVA gradually worsens with foveal involvement.
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Distrofias Hereditárias da Córnea/etiologia , Miopia Degenerativa/complicações , Refração Ocular/fisiologia , Acuidade Visual , Adolescente , Adulto , Fatores Etários , Idoso , Criança , China/epidemiologia , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/diagnóstico , Miopia Degenerativa/epidemiologia , Fatores Sexuais , Adulto JovemRESUMO
IMPORTANCE: Understanding visual impairment (VI) under different definitions and potential risk factors in high myopic is important for future myopia control. BACKGROUND: Limited studies exists investigating the VI among high myopic and with varying VI definitions. DESIGN: Registry cohort study. PARTICIPANTS: Eight hundred and eighty-four participants were from ZOC-BHVI study. METHODS: Subjects aged 7 to 70 years with high myopia were enrolled. Uncorrected visual acuity and best-corrected visual acuity (UCVA and BCVA), cycloplegic refraction, axial length (AL), corneal curvatures, anterior chamber depth and lens thickness were measured. Axial length/corneal radius of curvature ratio (AL/CR ratio) was calculated. Fundus lesions were graded into five categories. VI and blindness were defined based on the better-seeing eye according to the World Health Organization (WHO) criteria and US criteria. Multiple logistic regression analysis was used to assess risk factors for VI. MAIN OUTCOME MEASURES: Rates of VI and blindness. RESULTS: A total of 884 participants were included, with mean (SD) age 18.5 (12.4) years and 46.4% male. Rate of UCVI/blindness were 72.6%/27.3% and 17.9%/82.1% based on WHO and US criteria. With respect to BCVA, 4.1%/5.9% of participants had BCVI using two definitions, whereas the rate for blindness was 0.2% and 0.6%. After adjusting confounders, multiple logistic regression showed that more severe fundus lesions, greater AL/CR ratio were at a higher risk of being VI, both in two definitions (P < .005). CONCLUSIONS AND RELEVANCE: The rate of VI and blindness in highly myopic patients varies significantly using different definition. Severe fundus lesions and greater AL/CR ratios were associated with a higher risk of VI.
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Miopia , Baixa Visão , Adolescente , Estudos de Coortes , Feminino , Fundo de Olho , Humanos , Masculino , Miopia/complicações , Miopia/diagnóstico , Miopia/epidemiologia , Refração Ocular , Baixa Visão/diagnóstico , Baixa Visão/epidemiologia , Baixa Visão/etiologia , Acuidade VisualRESUMO
IMPORTANCE: Detection of early onset neovascular age-related macular degeneration (AMD) is critical to protecting vision. BACKGROUND: To describe the development and validation of a deep-learning algorithm (DLA) for the detection of neovascular age-related macular degeneration. DESIGN: Development and validation of a DLA using retrospective datasets. PARTICIPANTS: We developed and trained the DLA using 56 113 retinal images and an additional 86 162 images from an independent dataset to externally validate the DLA. All images were non-stereoscopic and retrospectively collected. METHODS: The internal validation dataset was derived from real-world clinical settings in China. Gold standard grading was assigned when consensus was reached by three individual ophthalmologists. The DLA classified 31 247 images as gradable and 24 866 as ungradable (poor quality or poor field definition). These ungradable images were used to create a classification model for image quality. Efficiency and diagnostic accuracy were tested using 86 162 images derived from the Melbourne Collaborative Cohort Study. Neovascular AMD and/or ungradable outcome in one or both eyes was considered referable. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: In the internal validation dataset, the AUC, sensitivity and specificity of the DLA for neovascular AMD was 0.995, 96.7%, 96.4%, respectively. Testing against the independent external dataset achieved an AUC, sensitivity and specificity of 0.967, 100% and 93.4%, respectively. More than 60% of false positive cases displayed other macular pathologies. Amongst the false negative cases (internal validation dataset only), over half (57.2%) proved to be undetected detachment of the neurosensory retina or RPE layer. CONCLUSIONS AND RELEVANCE: This DLA shows robust performance for the detection of neovascular AMD amongst retinal images from a multi-ethnic sample and under different imaging protocols. Further research is warranted to investigate where this technology could be best utilized within screening and research settings.
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Neovascularização de Coroide/diagnóstico , Aprendizado Profundo , Diagnóstico por Computador , Fotografação , Degeneração Macular Exsudativa/diagnóstico , Algoritmos , Área Sob a Curva , Reações Falso-Positivas , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmologistas , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Acuidade Visual/fisiologiaRESUMO
Purpose To compare the CT imaging performance of a carboxybetaine zwitterionic-coated tantalum oxide (TaCZ) nanoparticle CT contrast agent with that of a conventional iodinated contrast agent in a swine model meant to simulate overweight and obese patients. Materials and Methods Four swine were evaluated inside three different-sized adipose-equivalent encasements emulating abdominal girths of 102, 119, and 137 cm. Imaging was performed with a 64-detector row CT scanner at six scan delays after intravenous injection of 240 mg element (Ta or I) per kilogram of body weight of TaCZ or iopromide. For each time point, contrast enhancement of the aorta and liver were measured by using regions of interest. Two readers independently recorded the clarity of vasculature using a five-point Likert scale. Findings were compared by using paired t tests and Wilcoxon signed-rank tests. Results Mean peak enhancement was higher for TaCZ than for iopromide in the aorta (270 HU [σ = 24.5] vs 199 HU [σ = 10.2], P < .001) and liver (61.3 HU [σ = 11.7] vs 45.2 HU [σ = 8], P < .001). Vascular clarity was higher for TaCZ than for iopromide in 63% (132 of 208), 82% (170 of 208), and 86% (178 of 208) of the individual vessels at the 102-, 119-, and 137-cm girths, respectively (P < .01). Arterial clarity scores were higher for TaCZ than for iopromide in 62% (208 of 336) of vessels. Venous clarity scores were higher for TaCZ than for iopromide in 89% (128 of 144) of the veins in the venous phase and in 100% (144 of 144) of veins in the delayed phase (P < .01). No vessel showed higher clarity score with iopromide than with TaCZ. Conclusion An experimental tantalum nanoparticle-based contrast agent showed greater contrast enhancement compared with iopromide in swine models meant to simulate overweight and obese patients. © RSNA, 2018.
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Meios de Contraste/química , Obesidade/diagnóstico por imagem , Sobrepeso/diagnóstico por imagem , Óxidos/química , Tantálio/química , Tomografia Computadorizada por Raios X/métodos , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Feminino , Injeções Intravenosas , Nanopartículas/administração & dosagem , Nanopartículas/química , Óxidos/administração & dosagem , Suínos , Tantálio/administração & dosagem , Circunferência da CinturaRESUMO
PURPOSE: To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs. DESIGN: A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs. PARTICIPANTS: We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm. METHODS: This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm. MAIN OUTCOME MEASURES: The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON. RESULTS: In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%). CONCLUSIONS: A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologic myopia is the most common cause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results.
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Algoritmos , Aprendizado Profundo , Técnicas de Diagnóstico Oftalmológico/instrumentação , Glaucoma/complicações , Disco Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/diagnóstico , Fundo de Olho , Glaucoma/diagnóstico , Humanos , Doenças do Nervo Óptico/etiologia , Fotografação/métodos , Curva ROC , Estudos RetrospectivosRESUMO
It has been reported that miR-376a is involved in the formation and progression of several types of cancer. However, the expression and function of miR-376a is still unknown in non-small cell lung carcinomas (NSCLC). In this study, the expression of miR-376a in NSCLC tissues and cell lines were examined by real-time PCR, the effects of miR-376a on cell proliferation, apoptosis and invasion were evaluated in vitro. Luciferase reporter assay was performed to identify the targets of miR-376a. The results showed that miR-376a was significantly downregulated in NSCLC tissues and cell lines. Restoration of miR-376a in NSCLC cell line A549 significantly inhibited cell proliferation, increased cell apoptosis and suppressed cell invasion, compared with control-transfected A549 cells. Luciferase reporter assay showed that c-Myc, an oncogene that regulating cell survival, angiogenesis and metastasis, was a direct target of miR-376a. Over-expression of miR-376a decreased the mRNA and protein levels of c-Myc in A549 cells. In addition, upregulation of c-Myc inhibited miR-376a-induced inhibition of cell proliferation and invasion in A549 cells. Therefore, our results indicate a tumor suppressor role of miR-376a in NSCLC by targeting c-Myc. miR-376a may be a promising therapeutic target for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/genética , Genes myc , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/genética , Células A549 , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/biossíntese , MicroRNAs/metabolismo , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transcriptoma , TransfecçãoRESUMO
AIB1 was involved in the development and progression of breast cancer. Although it was found that AIB1 could be phosphorylated by some kinases including PI3K, the function of AIB1 and AKT interaction in breast cancer is not well defined. MCF-7 cells were transfected with pERE-Luc AKT and/or AIB1 plasmids, and then ERE luciferase activity in presence or absence of estrogen (E2) were measured. Plasmids containing PTEN and an PI3K inhibitor LY294002 were transfected into or treated cells to identify the interaction of PI3K/AKT and activation of AIB1, and examine their roles in cell cycle regulation. The AKT phosphorylation activity was evaluated by kinase assay using H2B as a substrate. The association between A1B1 and pS2 promoter was detected by the Chromatin Immunoprecipitation (ChIP) assay. AIB1 and AKT in the same complex were detected by Pull-down assay. IGF-1 can increase AIB1 recruitment to PS2 and enhance the ER-dependent transcription activity through the PI3K/AKT pathway. AIB1 associate with AKT to regulate cell cycle. The special relations concerning the AIB1 and AKT may arouse some new viewpoints for potential therapeutic targets in breast cancer.
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Neoplasias da Mama/patologia , Estradiol/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/fisiologia , Neoplasias Hormônio-Dependentes/patologia , Coativador 3 de Receptor Nuclear/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/fisiologia , Animais , Ciclo Celular/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Imunoprecipitação , Fator de Crescimento Insulin-Like I/farmacologia , Células MCF-7 , Camundongos , Proteínas de Neoplasias/genética , Coativador 3 de Receptor Nuclear/genética , Fosforilação , Presenilina-2/biossíntese , Presenilina-2/genética , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/fisiologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , TransfecçãoRESUMO
SIGNIFICANCE: Some studies reported that optic disc tilt and rotation might be risk factors for the susceptibility of high myopic eyes to develop glaucoma. However, data regarding optic disc manifestations in high myopia participants are few. It is crucial to characterize the features of optic disc manifestations among high myopes. PURPOSE: To describe optic disc characteristics of Chinese highly myopic eyes and to investigate associated factors. METHODS: This cross-sectional, observational study included 890 Chinese with bilateral high myopia (defined as ≤-6.00 diopters spherical power) in 2012. All subjects underwent cycloplegic autorefraction, ocular biometry, and fundus photography. The optic disc tilt ratio, degree of rotation, and ß-zone peripapillary atrophy area were measured from the 45°optic disc-centered fundus photographs. Optic disc tilt was defined as optic disc tilt ratio, the ratio of maximum to minimum diameter of optic disc, exceeding 1.3. The definition of optic disc rotation was using optic disc rotation degree, the angle from long diameter and the vertical meridian, of >15°. RESULTS: Among 890 participants, 2 were excluded by ungradable optic disc-centered fundus photographs. In the 888 studied right eyes, the mean spherical power was -9.36 ± 3.46 diopters with a mean axial length of 27.51 ± 1.63 mm. The proportion of optic disc tilting, rotation, and ß-zone peripapillary atrophy were 81.2%, 48.3%, and 92.8%, respectively. The mean ratio of optic disc tilting and rotation degree was 1.78 ± 0.53 and 21.08 ± 19.91°; the mean area of ß-zone peripapillary atrophy/optic disc head was 1.11 ± 1.22. A multiple linear regression showed that older age (P < .001), female (P = .02), and more myopic spherical equivalent (P = .005) were related to the greater optic disc tilting ratio. CONCLUSIONS: Beta-zone peripapillary atrophy, optic disc tilting, and rotation are very common in highly myopic eyes in Chinese population. Older age, female, and more myopic spherical equivalent are risk factors of higher degree of optic disc tilting.
Assuntos
Anormalidades do Olho/diagnóstico , Miopia Degenerativa/diagnóstico , Atrofia Óptica/diagnóstico , Disco Óptico/anormalidades , Adolescente , Adulto , Povo Asiático/etnologia , Biometria/métodos , Criança , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Anormalidades do Olho/etnologia , Feminino , Fundo de Olho , Humanos , Masculino , Miopia Degenerativa/etnologia , Atrofia Óptica/etnologia , Fotografação , Refração Ocular , Adulto JovemRESUMO
BACKGROUND This study aimed to explore the correlation between FGFR1 and clinical features, including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). FGFR1 gene amplification has been found in non-small cell lung cancer (NSCLC). However, the prognostic value of FGFR1 and the correlation between FGFR1 and clinical features are still controversial. MATERIAL AND METHODS A total of 92 patients with NSCLC who underwent R0 resection between July 2006 and July 2008 were enrolled in the study. The expression of FGFR1, VEGFR2, and CD34 was detected by immunohistochemistry. The correlations between the aforementioned markers and the patients' clinical features were analyzed by the chi-square test. The impact factors of prognosis were evaluated by Cox regression analyses. RESULTS The expression ratios of FGFR1 and VEGFR2 were 26.1% and 43.4%, respectively. The intensity of FGFR1 expression was related to VEGFR2 and histopathology. To some extent, the average microvessel density (MVD) had correlation to the expression of FGFR1 and VGEFR2. The pathological stages III-IV and high expression of FGFR1 were found to be independent prognostic factors. CONCLUSIONS The expression intensity of FGFR1 and VEGFR2 was associated with MVD, and the expression of FGFR1 is one of the independent prognostic indicators for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Neoplasias Pulmonares/enzimologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Antígenos CD34/metabolismo , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Microvasos/enzimologia , Microvasos/patologia , Pessoa de Meia-Idade , Neovascularização Patológica/enzimologia , Neovascularização Patológica/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Glucosamine (GlcN) and microbial transglutaminase (Tgase) are used separately or together to improve the emulsifying properties of whey protein isolate (WPI). However, little is known about how the emulsifying properties change when GlcN residues are incorporated into WPI cross-linked by Tgase. We used Tgase as a biocatalyst to cross-link WPI in the presence of GlcN in a liquid system for 12 h at a moderate temperature (25°C). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses indicated that protein polymerization and GlcN conjugation occurred simultaneously, phenomena also supported by the loss of free amines (9.4-20.5%). Addition of 5 U Tgase/g protein improved the emulsifying properties of moderately cross-linked WPI polymers. The Tgase-treated WPI polymers had a larger particle size (â¼2.6-fold) than native WPI, which may have reduced coalescence and flocculation in an oil-in-water emulsion system. However, the incorporation of GlcN residues into WPI, predominantly via enzymatic glycation, partly inhibited the cross-links between the WPI molecules catalyzed by Tgase, reducing the size of the WPI polymers 0.81- to 0.86-fold). Consequently, WPI+GlcN conjugates provided less stability to the emulsion. Moreover, high NaCl concentration (0.2 M) decreased the emulsifying properties of the WPI+GlcN conjugates by neutralizing negative electric charges in the glycoconjugates. However, the improved emulsifying properties of WPI cross-linked by Tgase may be useful in food processing at higher NaCl concentrations due to the formation of the thicker steric barrier at the oil-water interface.
Assuntos
Proteínas do Leite/metabolismo , Proteínas do Soro do Leite , Animais , Emulsões/química , Glucosamina , Transglutaminases/metabolismoRESUMO
BACKGROUND: Different techniques have been applied to alter myofibril protein (MP) structure, which further promotes protein-protein interactions and influencing the MP gelling characteristics. Influence of BslA from natto food (protein concentration, 30 mg mL-1 ; at 0.001, 0.005, 0.01, 0.05 and 0.1 g kg-1 ) on the characteristics of MP gel of chicken breast was investigated. RESULTS: Results show that cooking loss significantly (P < 0.05) decreased with increased percentage of BslA. Hardness of MP gel did not significantly change at 0.01 g kg-1 BslA. Differential scanning calorimetry disclosed that MP was modified by the addition of BslA. Moreover, BslA produced a high value of storage modulus (G') and low value of phase angle (tan δ) during heating, especially at 0.01 g kg-1 . Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis proved the formation of higher-molecular-weight polymers by developing non-disulfide covalent bonds between MP at 0.01 g kg-1 BslA. Surface hydrophobicity of the MP gel was decreased with increased percentage of BslA. Scanning electron microscopy confirmed the increasing number of uniform cavities of MP gel with the increased percentage of BslA. CONCLUSION: Addition of 0.01 g kg-1 BslA significantly improved the water holding capacity and rheological properties of MP by developing non-disulfide covalent bonds. © 2017 Society of Chemical Industry.