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Recently, as technology has advanced, the use of in-vehicle infotainment systems has increased, providing many functions. However, if the driver's attention is diverted to control these systems, it can cause a fatal accident, and thus human-vehicle interaction is becoming more important. Therefore, in this paper, we propose a human-vehicle interaction system to reduce driver distraction during driving. We used voice and continuous-wave radar sensors that require low complexity for application to vehicle environments as resource-constrained platforms. The proposed system applies sensor fusion techniques to improve the limit of single-sensor monitoring. In addition, we used a binarized convolutional neural network algorithm, which significantly reduces the computational workload of the convolutional neural network in command classification. As a result of performance evaluation in noisy and cluttered environments, the proposed system showed a recognition accuracy of 96.4%, an improvement of 7.6% compared to a single voice sensor-based system, and 9.0% compared to a single radar sensor-based system.
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Conducción de Automóvil , Voz , Algoritmos , Humanos , Redes Neurales de la Computación , RadarRESUMEN
BACKGROUND: Therapeutic interventions in the insulin-like growth factor receptor (IGF-1R) pathway were expected to provide clinical benefits; however, IGF-1R tyrosine kinase inhibitors (TKIs) have shown limited antitumor efficacy, and the mechanisms conveying resistance to these agents remain elusive. METHODS: The expression and activation of the IGF-1R and Src were assessed via the analysis of a publicly available dataset, as well as immunohistochemistry, Western blotting, RT-PCR, and in vitro kinase assays. The efficacy of IGF-1R TKIs alone or in combination with Src inhibitors was analyzed using MTT assays, colony formation assays, flow cytometric analysis, and xenograft tumor models. RESULTS: The co-activation of IGF-1R and Src was observed in multiple human NSCLC cell lines as well as in a tissue microarray (n = 353). The IGF-1R and Src proteins mutually phosphorylate on their autophosphorylation sites. In high-pSrc-expressing NSCLC cells, linsitinib treatment initially inactivated the IGF-1R pathway but led a Src-dependent reactivation of downstream effectors. In low-pSrc-expressing NSCLC cells, linsitinib treatment decreased the turnover of the IGF-1R and Src proteins, ultimately amplifying the reciprocal co-activation of IGF-1R and Src. Co-targeting IGF-1R and Src significantly suppressed the proliferation and tumor growth of both high-pSrc-expressing and low-pSrc-expressing NSCLC cells in vitro and in vivo and the growth of patient-derived tissues in vivo. CONCLUSIONS: Reciprocal activation between Src and IGF-1R occurs in NSCLC. Src causes IGF-1R TKI resistance by acting as a key downstream modulator of the cross-talk between multiple membrane receptors. Targeting Src is a clinically applicable strategy to overcome resistance to IGF-1R TKIs.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Molecular Dirigida , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Familia-src Quinasas/metabolismo , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Imidazoles/farmacología , Neoplasias Pulmonares/patología , Ratones , Modelos Biológicos , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estabilidad Proteica/efectos de los fármacos , Pirazinas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Recent studies have shown that glucosamine inhibits the proliferation of various human cancer cell lines and downregulates the activity of COX-2, HIF-1α, p70S6K, and transglutaminase 2. Because the IGF-1R/Akt pathway is a common upstream regulator of p70S6K, HIF-1α, and COX-2, we hypothesized that glucosamine inhibits cancer cell proliferation through this pathway. METHODS: We used various in vitro assays including flow cytometry assays, small interfering RNA (siRNA) transfection, western blot analysis, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, reverse transcription-polymerase chain reaction, and in vivo xenograft mouse model to confirm anticancer activities of glucosamine and to investigate the molecular mechanism. RESULTS: We found that glucosamine inhibited the growth of human non-small cell lung cancer (NSCLC) cells and negatively regulated the expression of IGF-1R and phosphorylation of Akt. Glucosamine decreased the stability of IGF-1R and induced its proteasomal degradation by increasing the levels of abnormal glycosylation on IGF-1R. Moreover, picropodophyllin, a selective inhibitor of IGF-1R, and the IGF-1R blocking antibody IMC-A12 induced significant cell growth inhibition in glucosamine-sensitive, but not glucosamine-resistant cell lines. Using in vivo xenograft model, we confirmed that glucosamine prohibits primary tumor growth through reducing IGF-1R signalling and increasing ER-stress. CONCLUSIONS: Taken together, our results suggest that targeting the IGF-1R/Akt pathway with glucosamine may be an effective therapeutic strategy for treating some type of cancer.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Glucosamina/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/genética , Receptor IGF Tipo 1/metabolismo , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Estrés del Retículo Endoplásmico/efectos de los fármacos , Glicosilación , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Terapia Molecular Dirigida , Fosforilación , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica , Interferencia de ARN , Receptor IGF Tipo 1/genética , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Effects of autoxidation and light irradiation on the oxidative stability were evaluated in rice oil from two brown rice flours including 'Baromi2' and 'Samkwang'. 'Baromi2' is a newly developed variety for rice flour production while 'Samkwang' is a typical rice variety as a control. Degree of oxidation and volatile profiles were evaluated in rice oil stored at 60 °C or under fluorescent light at 25 °C. The oil yields of 'Baromi2' and 'Samkang' were 2.63 and 1.78%, respectively whereas rice oil from 'Baromi2' had lower degree of unsaturation than 'Samkang'. Rice oil from 'Samkwang' possessed higher volatile compounds and more oxidized products during autoxidation whereas rice oil from 'Baromi2' had more oxidation products under light irradiation. Hexanal and 2-heptenal were major headspace volatile from heated rice oil while 2-heptenal and 1-octene-3-ol were main volatiles from light irradiated rice oil, which implies the involvement of singlet oxygen in rice oil during photooxidation.
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The oxidation of copper and its surface oxides are gaining increasing attention due to the enhanced CO2 reduction reaction (CO2RR) activity exhibited by partially oxidized copper among the copper-based catalysts. The "8" surface oxide on Cu(111) is seen as a promising structure for further study due to its resemblance to the highly active Cu2O(110) surface in the C-C coupling of the CO2RR, setting it apart from other O/Cu(111) surface oxides resembling Cu2O(111). However, recent X-ray photoelectron spectroscopy analysis challenges the currently accepted atomic structure of the "8" surface oxide, prompting a need for reevaluation. This study highlights the limitations of conventional methods when addressing such challenges, leading us to adopt global optimization search techniques. After a rigorous process to ensure robustness, the unbiased global minimum of the "8" surface oxide is identified. Interestingly, this configuration differs significantly from other surface oxides and also from previous "8" models while retaining similarities to the Cu2O(110) surface.
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In the recent era of green and sustainable energy, the demand for effective and efficient energy harvesting has dramatically increased. Piezoelectric energy harvesting, which converts mechanical energy into electrical energy, is considered a viable strategy to achieve this goal. Janus-type nanomaterial, a noncentrosymmetric material with different elemental species in the upper and lower atomic layers, has gained interest due to its exotic properties compared to conventional bulk and symmetric materials. In this work, we systematically design and investigate a new class of Janus nanomaterials with enhanced intrinsic polarization via the successive ionic exchange method. Multiple layers of stability standards, including both thermodynamic and dynamic stabilities, are employed in the high-throughput screening procedure of novel Janus-type nanomaterials. The newly proposed Janus-type nanomaterials exhibit more than 10 times higher piezoelectric response compared to that of reported low-dimensional materials and even comparable to that of bulk materials.
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The near-infrared (NIR) sensor technology is crucial for various applications such as autonomous driving and biometric tracking. Silicon photodetectors (SiPDs) are widely used in NIR applications; however, their scalability is limited by their crystalline properties. Organic photodetectors (OPDs) have attracted attention for NIR applications owing to their scalability, low-temperature processing, and notably low dark current density (JD), which is similar to that of SiPDs. However, the still high JD (at NIR band) and few measurements of noise equivalent powers (NEPs) pose challenges for accurate performance comparisons. This study addresses these issues by quantitatively characterizing the performance matrix and JD generation mechanism using electron-blocking layers (EBLs) in OPDs. The energy offset at an EBL/photosensitive layer interface determines the thermal activation energy and directly affects JD. A newly synthesized EBL (3PAFBr) substantially enhances the interfacial energy barrier by forming a homogeneous contact owing to the improved anchoring ability of 3PAFBr. As a result, the OPD with 3PAFBr yields a noise current of 852 aA (JD = 12.3 fA cmâ»2 at V â -0.1 V) and several femtowatt-scale NEPs. As far as it is known, this is an ultralow of JD in NIR OPDs. This emphasizes the necessity for quantitative performance characterization.
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CXCL14 is a chemokine family member that is involved in various cellular responses in addition to immune cell activation. Although constitutive CXCL14 expression in normal epithelial cells may help protect against infection by activating immune systems, its expression in cancer cells has raised controversy regarding its possible role in tumorigenesis. However, the underlying mechanisms for this disparity remain unknown. Investigation of cellular CXCL14 binding properties might increase our understanding of the peptide's roles in tumorigenesis. In the present study, we found that CXCL14 binds to various cell types. Interestingly, binding to NCI-H460 cells was prevented by heparan sulfate and N-acetyl neuraminic acid. Next, we examined effect of CXCL14 binding in NCI-H460 and NCI-H23. CXCL14 enhanced proliferation and migration in NCI-H460 but had no effect on NCI-H23. A reporter gene assay with various transcription factor response elements revealed that only nuclear factor-κB (NF-κB) signaling was activated by CXCL14 in NCI-H460 cells, which was blocked by BAPTA-AM, TPCA-1, and brefeldin A. Exogenous expression of some glycoproteins such as syndecan-4, podoplanin, and CD43 in these cells enhanced CXCL14 binding and NF-κB activity. Collectively, these results demonstrate that CXCL14 binding to glycoproteins harboring heparan sulfate proteoglycans and sialic acids leads proliferation and migration of some cancer cells.
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Movimiento Celular/efectos de los fármacos , Quimiocinas CXC/farmacología , Glicoproteínas/metabolismo , Heparitina Sulfato/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ácido N-Acetilneuramínico/metabolismo , Señalización del Calcio/efectos de los fármacos , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Endocitosis/efectos de los fármacos , Células HEK293 , Humanos , FN-kappa B/metabolismo , Unión Proteica/efectos de los fármacos , Receptores Fc/metabolismoRESUMEN
Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGF-independent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non-small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3-treated non-small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3-induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. Future studies are needed for development of IGFBP-3 as a new line of antiangiogengic cancer drug.
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Inhibidores de la Angiogénesis/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Neovascularización Patológica/tratamiento farmacológico , Regiones Promotoras Genéticas/efectos de los fármacos , Transcripción Genética/efectos de los fármacos , Proteína Elk-1 con Dominio ets/metabolismo , Inhibidores de la Angiogénesis/metabolismo , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Carcinoma/irrigación sanguínea , Carcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Células Cultivadas/citología , Células Cultivadas/efectos de los fármacos , Embrión de Pollo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Femenino , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/patología , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/uso terapéutico , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Organismos Libres de Patógenos Específicos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Some of ginsenosides, root extracts from Panax ginseng, exert cytotoxicity against cancer cells through disruption of membrane subdomains called lipid rafts. Protopanaxadiol (PPD) exhibits the highest cytotoxic effect among 8 ginsenosides which we evaluated for anti-cancer activity. We investigated if PPD disrupts lipid rafts in its cytotoxic effects and also the possible mechanisms. METHODS: Eight ginsenosides were evaluated using different cancer cells and cell viability assays. The potent ginsenoside, PPD was investigated for its roles in lipid raft disruption and downstream pathways to apoptosis of cancer cells. Anti-cancer effects of PPD was also investigated in vivo using mouse xenograft model. RESULTS: PPD consistently exerts its potent cytotoxicity in 2 cell survival assays using 5 different cancer cell lines. PPD disrupts lipid rafts in different ways from methyl-ß-cyclodextrin (MßCD) depleting cholesterol out of the subdomains, since lipid raft proteins were differentially modulated by the saponin. During disruption of lipid rafts, PPD activated neutral sphingomyelinase 2 (nSMase 2) hydrolyzing membrane sphingomyelins into pro-apoptotic intracellular ceramides. Furthermore, PPD demonstrated its anti-cancer activities against K562 tumor cells in mouse xenograft model, confirming its potential as an adjunct or chemotherapeutic agent by itself in vivo. CONCLUSIONS: This study demonstrates that neutral sphingomyelinase 2 is responsible for the cytotoxicity of PPD through production of apoptotic ceramides from membrane sphingomyelins. Thus neutral sphingomyelinase 2 and its relevant mechanisms may potentially be employed in cancer chemotherapies.
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Citotoxinas/administración & dosificación , Ginsenósidos/administración & dosificación , Neoplasias/tratamiento farmacológico , Panax/química , Sapogeninas/administración & dosificación , Esfingomielina Fosfodiesterasa/metabolismo , Animales , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Neoplasias/enzimología , Neoplasias/genética , Esfingomielina Fosfodiesterasa/genéticaRESUMEN
Colorectal cancer (CRC) is common cancer worldwide, and the 5year relative survival rate of CRC patients with distant metastasis is as low as 14%. Therefore, identifying markers of CRC is important for the early detection of CRC and applying appropriate treatment strategies. The lymphocyte antigen 6 family (LY6 family) is closely related to the behavior of various cancer types. Among the LY6 family, the lymphocyte antigen 6 complex, locus E (LY6E), which is specifically highly expressed in CRC. Hence, the effects of LY6E on cell function in CRC and its role in CRC recurrence and metastasis were investigated. Reverse transcriptionquantitative PCR, western blotting and in vitro functional studies were carried out using four CRC cell lines. Immunohistochemical analysis of 110 CRC tissues was performed to explore the biological functions and expression patterns of LY6E in CRC. LY6E was overexpressed CRC tissues compared with that in adjacent normal tissues. High expression of LY6E in CRC tissues was an independent prognostic factor of worse overall survival (P=0.048). Knockdown of LY6E using small interfering RNA inhibited CRC cell proliferation, migration, invasion, and soft agar colony formation, indicating some of its effects on CRC carcinogenic functions. High expression of LY6E may have oncogenic functions in CRC and be useful as a valuable prognostic marker and potential therapeutic target for CRC.
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Carcinogénesis , Neoplasias Colorrectales , Humanos , Antígenos de Superficie , Western Blotting , Neoplasias Colorrectales/genética , Proteínas Ligadas a GPI , PronósticoRESUMEN
Dielectric scatterers where Mie resonances can be excited in both electric and magnetic modes have emerged as a promising candidate for efficient light trapping (LT) in thin-film solar cells. We present that light absorption in organic solar cells (OSCs) can be significantly enhanced by a front-sided incorporation of a core-shell nanostructure consisting of a high-refractive-index dielectric nanosphere array conformally coated with a low-refractive-index dielectric layer. Strong forward light scattering of the all-dielectric LT structure enables the absorption in an organic semiconductor to be remarkably boosted over a broad range of wavelengths, which is attributed to interference of a simultaneous excitation of the electric and magnetic dipole resonant modes. The OSC with the LT structure shows the short-circuit current density (Jsc) of 28.23 mA/cm2, which is 10% higher than that of a flat OSC. We also explore how the LT structure affects scattering cross-sections, spectral multipole resonances, and far-field radiation patterns. The approach described in this work could offer the possibility for the improvement of characteristic performances of various applications, such as other thin-film solar cells, photodiodes, light-emitting diodes, and absorbers.
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Bioelectronic devices that offer real-time measurements, biological signal processing, and continuous monitoring while maintaining stable performance are in high demand. The materials used in organic electrochemical transistors (OECTs) demonstrate high transconductance (GM) and excellent biocompatibility, making them suitable for bioelectronics in a biological environment. However, ion migration in OECTs induces a delayed response time and low cut-off frequency, and the adverse biological environment causes OECT durability problems. Herein, we present OECTs with a faster response time and improved durability, made possible by using a nanofiber mat channel of a conventional OECT structure. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/polyacrylamide (PAAm) nanofiber mat channel OECTs are fabricated and subjected to various durability tests for the first time based on continuous measurements and mechanical stability assessments. The results indicate that the nanofiber mat channel OECTs have a faster response time and longer life spans compared to those of film channel OECTs. The improvements can be attributed to the increased surface area and fibrous structure of the nanofiber mat channel. Furthermore, the hydrogel helps to maintain the structure of the nanofiber, facilitates material exchange, and eliminates the need for a crosslinker.
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Angiogenesis, the process by which new blood vessels are recruited to existing ones, is essential for tumor development. Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), which modulates bioavailability of IGF, has been studied for its potential role in angiogenesis during tissue regeneration and cancer development. In this study, we assessed the role of IGFBP-3 in tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC) and human umbilical vein endothelial cells (HUVECs) using adenoviral (Ad-BP3) and recombinant (rBP3) IGFBP-3. Using an in vivo orthotopic tongue tumor model, we confirmed that both Ad-BP3 and rBP3 suppress the growth of UMSCC38 HNSCC cells in vivo. Ad-BP3 inhibited vascularization in tongue tumors and chorio-allantoic membrane, and suppressed angiogenesis-stimulating activities in UMSCC38 cells. In HUVECs, Ad-BP3 decreased migration, invasion, and tube formation. rBP3 also suppressed production of vascular endothelial growth factor (VEGF) in HUVECs and UMSCC38 cells. IGFBP-3-GGG, a mutant IGFBP-3 with loss of IGF binding capacity, suppressed VEGF production. In addition, we found that IGFBP-3 suppressed VEGF expression, even in mouse embryonic fibroblasts from an IGF-1R-null mouse. Finally, we demonstrated that IGFBP-3-GGG inhibits tumor angiogenesis and growth to the same degree as wild-type IGFBP-3. Taken together, these results support the hypothesis that IGFBP-3 has anti-angiogenic activity in HNSCC, at least in part due to IGF-independent suppression of VEGF production from vascular endothelial cells and cancer cells.
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Carcinoma de Células Escamosas/irrigación sanguínea , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/patología , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neovascularización Patológica/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adenoviridae/genética , Animales , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Línea Celular Tumoral , Movimiento Celular , Células Cultivadas , Embrión de Pollo , Femenino , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Neoplasias de Cabeza y Cuello/terapia , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Inmunohistoquímica , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Ratones , Ratones Noqueados , Ratones Desnudos , Mutación , Neovascularización Patológica/terapia , Neovascularización Fisiológica/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carga Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
To expand the unchartered materials space of lead-free ferroelectrics for smart digital technologies, tuning their compositional complexity via multicomponent alloying allows access to enhanced polar properties. The role of isovalent A-site in binary potassium niobate alloys, (K,A)NbO3 using first-principles calculations is investigated. Specifically, various alloy compositions of (K,A)NbO3 are considered and their mixing thermodynamics and associated polar properties are examined. To establish structure-property design rules for high-performance ferroelectrics, the sure independence screening sparsifying operator (SISSO) method is employed to extract key features to explain the A-site driven polarization in (K,A)NbO3 . Using a new metric of agreement via feature-assisted regression and classification, the SISSO model is further extended to predict A-site driven polarization in multicomponent systems as a function of alloy composition, reducing the prediction errors to less than 1%. With the machine learning model outlined in this work, a polarity-composition map is established to aid the development of new multicomponent lead-free polar oxides which can offer up to 25% boosting in A-site driven polarization and achieving more than 150% of the total polarization in pristine KNbO3 . This study offers a design-based rational route to develop lead-free multicomponent ferroelectric oxides for niche information technologies.
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Epidermal growth factor receptor (EGFR) is one of the most promising targets for cancer therapy. Here, we show the in vitro and in vivo anticancer effects and associated mechanisms of KO-202125, one of the synthesized aristolactam analogs, as a novel EGFR inhibitor, in EGFR-overexpressing cancer cell lines. KO-202125 showed more effective growth inhibition and apoptosis induction than gefitinib, a representative EGFR inhibitor, in various EGFR-overexpressing human cancers including estrogen receptor (ER)-negative MDA-MB-231 human breast cancer cells. Epidermal growth factor receptor phosphorylation at Tyr1068 was reduced and, consequently, the association of EGFR with p85 was decreased by KO-202125 treatment in MDA-MB-231 cell lines. This led to inactivation of the PI3K/Akt pathway, and consequently suppression of activation of the Wnt pathway and enhancement of the nuclear import of p27Kip1. KO-202125 treatment in nude mice injected with MDA-MB-231 cells showed inhibition of tumor growth without toxicity. Collectively, our results showed the possibility of KO-202125 as an effective therapy agent of EGFR-overexpressing cancer cells through reduced EGFR activity and downregulation of the Akt pathway.
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Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Isoindoles/farmacología , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/análisis , Ratones , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Receptores de Estrógenos/análisis , Transducción de Señal/efectos de los fármacos , Proteínas Wnt/fisiología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND AIMS: Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT-MSC) represent a novel tool for delivering therapeutic genes to tumor cells. Interferon (IFN)-ß is a cytokine with pleiotropic cellular functions, including anti-proliferative, immunomodulatory and anti-angiogenic activities. The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN-ß and to evaluate the anti-tumor effect of cAT-MSC-IFN-ß combined with cisplatin in mouse melanoma model. METHODS: cAT-MSC engineered to express mouse IFN-ß were generated using a lentiviral vector (cAT-MSC-IFN-ß) and the secreted IFN-ß-induced inhibition of tumor cell growth and apoptosis on B16F10 cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6 mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days later the engineered cAT-MSC were injected subcutaneously every 3 days to death. Tumor volume and survival times were measured. RESULTS: The combination treatment of cAT-MSC-IFN-ß with cisplatin was more effective in inhibiting the growth of melanoma and resulted in significantly extended survival time than both an unengineered cAT-MSC-cisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSC-IFN-ß were migrated to tumor sites. CONCLUSIONS: Our data suggest that canine AT-MSC could serve as a powerful cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions. Maximal anti-tumor effects were seen when this therapy was combined with a DNA-damaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN-ß in treating canine and human cancer patients.
Asunto(s)
Cisplatino/administración & dosificación , Interferón beta/metabolismo , Melanoma Experimental/terapia , Células Madre Mesenquimatosas/metabolismo , Trasplante de Células Madre , Tejido Adiposo/citología , Animales , Procesos de Crecimiento Celular/efectos de los fármacos , Movimiento Celular , Modelos Animales de Enfermedad , Perros , Sistemas de Liberación de Medicamentos , Ingeniería Genética , Terapia Genética , Humanos , Interferón beta/genética , Interferón beta/inmunología , Melanoma Experimental/genética , Melanoma Experimental/patología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos C57BL , Carga TumoralRESUMEN
Organic neuromorphic computing/sensing platforms are a promising concept for local monitoring and processing of biological signals in real time. Neuromorphic devices and sensors with low conductance for low power consumption and high conductance for low-impedance sensing are desired. However, it has been a struggle to find materials and fabrication methods that satisfy both of these properties simultaneously in a single substrate. Here, nanofiber channels with a self-formed ion-blocking layer are fabricated to create organic electrochemical transistors (OECTs) that can be tailored to achieve low-power neuromorphic computing and fast-response sensing by transferring different amounts of electrospun nanofibers to each device. With their nanofiber architecture, the OECTs exhibit a low switching energy of 113 fJ and operate within a wide bandwidth (cut-off frequency of 13.5 kHz), opening a new paradigm for energy-efficient neuromorphic computing/sensing platforms in a biological environment without the leakage of personal information.
Asunto(s)
Técnicas Biosensibles/instrumentación , Técnicas Electroquímicas/métodos , Nanofibras/química , Polímeros/química , Sinapsis/fisiología , Transistores Electrónicos/normas , Redes Neurales de la ComputaciónRESUMEN
Protein quantification techniques such as immunoassays have been improved considerably, but they have several limitations, including time-consuming procedures, low sensitivity, and extrinsic detection. Because direct surface-enhanced Raman spectroscopy (SERS) can detect intrinsic signals of proteins, it can be used as an effective detection method. However, owing to the complexity and reliability of SERS signals, SERS is rarely adopted for quantification without a purified target protein. This study reports an efficient and effective direct SERS-based immunoassay (SERSIA) technique for protein quantification and imaging. SERSIA relies on the uniform coating of gold nanoparticles (GNPs) on a target-protein-immobilized substrate by simple centrifugation. As centrifugation induces close contact between the GNPs and target proteins, the intrinsic signals of the target protein can be detected. For quantification, the protein levels in a cell lysate are estimated using similarity analysis between antibody-only and protein-conjugated samples. This method reliably estimates the protein level at a sub-picomolar detection limit. Furthermore, this method enables quantitative imaging of immobilized protein at a micrometer range. Because this technique is fast, sensitive, and requires only one type of antibody, this approach can be a useful method to detect proteins in biological samples.
RESUMEN
Selective chemical control of multiple reactions is incredibly important for the fabrication of sophisticated nanostructures for functional applications. A representative example is the synthesis of plasmonic nanomaterial-silver chloride (AgCl) conjugates, where metal ions should be selectively reduced into metallic nanostructures for plasmon-enhanced catalytic activity, while the reducible AgCl nanomaterials remain intact despite the presence of a chemical reductant. In addition to the selectively controlled reduction, the plasmonic nanostructures should be appropriately designed for the high stability and photoefficiency of catalysts. In this study, we demonstrate how AgCl nanocubes and nanospheres could be comprehensively wrapped by plasmonic three-dimensional nanomesh structures consisting of gold, silver, and palladium by the selective reduction of their ionic precursors while the AgCl nanostructures remain intact. Complete trimetallic wrapping provided the absorption of visible light, while the porosity of the nanomesh structures exposed the photocatalytic AgCl surface to catalyze desired reactions. Platinum in place of palladium was examined to demonstrate the versatility of the wrapping scheme, resulting in an extraordinary catalytic activity. Importantly, the detailed chemical mechanism behind the trimetallic wrapping of the AgCl nanostructures was systematically investigated to understand the roles of each reaction component in controlling the chemical selectivity. The synthesized AgCl-trimetal nanoconjugates excellently exhibit both metal-based and plasmon-enhanced catalytic properties for the removal of environmentally harmful Cr6+. Moreover, their applications as surface-enhanced Raman-scattering (SERS) probes for the in situ monitoring of catalytic reduction in real-time and as single-nanoparticle SERS probes for molecular detection are thoroughly demonstrated.