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Lipidated ATG8/LC3 proteins are recruited to single membrane compartments as well as autophagosomes, supporting their functions. Although recent studies have shown that Golgi-LC3 lipidation follows Golgi damage, its molecular mechanism and function under Golgi stress remain unknown. Here, by combining DLK1 overexpression as a new strategy for induction of Golgi-specific LC3 lipidation, and the application of Golgi-damaging reagents, we unravel the mechanism and role of Golgi-LC3 lipidation. Upon DLK1 overexpression, LC3 is lipidated on the Golgi apparatus in an ATG12-ATG5-ATG16L1 complex-dependent manner; a post-Golgi trafficking blockade is the primary cause of this lipidation. During Golgi stress, ATG16L1 is recruited through its interaction with V-ATPase for Golgi-LC3 lipidation. After post-Golgi trafficking inhibition, TFE3, a key regulator of the Golgi stress response, is translocated to the nucleus. Defects in LC3 lipidation disrupt this translocation, leading to an attenuation of the Golgi stress response. Together, our results reveal the mechanism and unexplored function of Golgi-LC3 lipidation in the Golgi stress response.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Aparato de Golgi , Proteínas Asociadas a Microtúbulos , Aparato de Golgi/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Humanos , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Células HeLa , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Estrés FisiológicoRESUMEN
Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 (ATP binding cassette subfamily B member 1) overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.
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Adenosina Trifosfatasas , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Ratas , Ratones , Animales , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Línea Celular , Cromatina , Mamíferos/genética , Antagonistas de Receptores Androgénicos , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Animales , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunología , Humanos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ratones Endogámicos C57BL , Femenino , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Línea Celular Tumoral , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Inmunoterapia/métodosRESUMEN
In smart cities, a large amount of optical camera equipment is deployed and used. Closed-circuit television (CCTV), unmanned aerial vehicles (UAVs), and smartphones are some examples of such equipment. However, additional information about these devices, such as 3D position, orientation information, and principal distance, is not provided. To solve this problem, the structured mobile mapping system point cloud was used in this study to investigate methods of estimating the principal point, position, and orientation of optical sensors without initial given values. The principal distance was calculated using two direct linear transformation (DLT) models and a perspective projection model. Methods for estimating position and orientation were discussed, and their stability was tested using real-world sensors. When the perspective projection model was used, the camera position and orientation were best estimated. The original DLT model had a significant error in the orientation estimation. The correlation between the DLT model parameters was thought to have influenced the estimation result. When the perspective projection model was used, the position and orientation errors were 0.80 m and 2.55°, respectively. However, when using a fixed-wing UAV, the estimated result was not properly produced owing to ground control point placement problems.
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Teléfono Inteligente , Dispositivos Aéreos No Tripulados , Ciudades , Modelos LinealesRESUMEN
This paper proposes a novel phase-resolved partial discharge (PRPD) sensor embedded in a MV-class bushing for high-accuracy insulation analysis. The design, fabrication, and evaluation of a PRPD sensor embedded in a MV-class bushing aimed to achieve the detection of partial discharge (PD) pulses that are phase-synchronized with the applied primary HV signal. A prototype PRPD sensor was composed of a flexible printed circuit board (PCB) with dual-sensing electrodes, utilizing a capacitive voltage divider (CVD) for voltage measurement, the D-dot principle for PD detection, and a signal transducer with passive elements. A PD simulator was prepared to emulate typical PD defects, i.e., a metal protrusion. The voltage measurement precision of the prototype PRPD sensor was satisfied with the accuracy class of 0.2 specified in IEC 61869-11, as the maximum corrected voltage error ratios and corrected phase errors in 80%, 100%, and 120% of the rated voltage (13.2 kilovolts (kV)) were less than 0.2% and 10 min, respectively. In addition, the prototype PRPD sensor had good linearity and high sensitivity for PD detection compared with a conventional electrical detection method. According to performance evaluation tests, the prototype PRPD sensor embedded in the MV-class bushing can measure PRPD patterns phase-synchronized with the primary voltage without any additional synchronization equipment or system. Therefore, the prototype PRPD sensor holds potential as a substitute for conventional commercial PD sensors. Consequently, this advancement could lead to the enhancement of power system monitoring and maintenance, contributing to the digitalization and minimization of power apparatus.
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Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa, the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.
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Antibacterianos , Pseudomonas aeruginosa , Animales , Humanos , Farmacorresistencia Microbiana/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Through the formation of an electron donor-acceptor (EDA) complex, strain-release aminopyridylation of [1.1.1]propellane with N-aminopyridinium salts as bifunctional reagents enabled the direct installation of amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in the absence of an external photocatalyst. The robustness of this method to synthesize 1,3-aminopyridylated BCPs under mild and metal-free conditions is highlighted by the late-stage modification of structurally complex biorelevant molecules. Moreover, the strategy was extended to P-centered and CF3 radicals for the unprecedented incorporation of such functional groups with pyridine across the BCP core in a three-component coupling. This practical method lays the foundation for the straightforward construction of new valuable C4-pyridine-functionalized BCP chemical entities, thus significantly expanding the range of accessibility of BCP-type bioisosteres for applications in drug discovery.
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The semi-enclosed estuary is very susceptible to changes in the physical and environmental characteristics of the inflow from the land. Therefore, continuous and comprehensive monitoring of such changes is necessary for managing the estuary. Nevertheless, the procedure or framework has not been proposed appropriately to determine how many instruments are necessary and where they need to be monitored and standardized to detect critical changes. The present work proposes a systematical strategy for the deployments of the monitoring array by using the combination of graphical optimization with the objective mapping technique. In order to reflect the spatiotemporal characteristics of the bay, the representative variables and eigenvectors were determined by the Empirical Orthogonal Function (EOF), and the cosine angle among them calculated and used as a design index of optimization. At the recommended locations, the sampled representative variables were interpolated to reconstruct their spatiotemporal distribution and compared with the true distribution. The analysis confirmed that the selected locations, even with a minimal number of points, can be used for on-site monitoring. In addition, the present framework suggests how to determine installable regions for real-time monitoring stations, which reflect the global and local characteristics of the semi-enclosed estuary.
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This paper proposes a technique to estimate the distance between an object and a rolling shutter camera using a single image. The implementation of this technique uses the principle of the rolling shutter effect (RSE), a distortion within the rolling-shutter-type camera. The proposed technique has a mathematical strength compared to other single photo-based distance estimation methods that do not consider the geometric arrangement. The relationship between the distance and RSE angle was derived using the camera parameters (focal length, shutter speed, image size, etc.). Mathematical equations were derived for three different scenarios. The mathematical model was verified through experiments using a Nikon D750 and Nikkor 50 mm lens mounted on a car with varying speeds, object distances, and camera parameters. The results show that the mathematical model provides an accurate distance estimation of an object. The distance estimation error using the RSE due to the change in speed remained stable at approximately 10 cm. However, when the distance between the object and camera was more than 10 m, the estimated distance was sensitive to the RSE and the error increased dramatically.
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A general strategy for visible-light-enabled site-selective trifluoromethylative pyridylation of unactivated alkenes has been developed using pyridines and triflic anhydride (Tf2 O). Intriguingly, the N-triflylpyridinium salts, generated in situ from pyridines and Tf2 O, serve as effective modular bifunctional reagents to install both CF3 and pyridyl groups to various olefins while controlling C4-selectivity in radical addition to the pyridine core. This synthetic route exhibited broad substrate scope under metal-free and mild photocatalytic conditions, granting efficient access to valuable C4-alkylated pyridines and quinolines without requiring prefunctionalization of the reaction site.
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Sensors and electronic devices based on semiconductors in their two-dimensional forms have many advantages. In this paper, we studied micro-Hall sensors based on two-dimensional molybdenum diselenide for the first time. The micro-Hall sensor based on a Ti/MoSe2/Ti structure clearly showed a linear dependence of the Hall voltage as a function of the magnetic field, with a magnetic sensitivity of â¼16 V/AT. The magnetic sensitivity was higher in the Au/MoSe2/Au structure, with a maximum value of â¼120 V/AT at a bias current of 100 mA; the minimum detectable magnetic field was found to be 1.45 µT/Hz1/2 at the same current value, making our new micro-Hall sensor a very good candidate for magnetic sensing applications.
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Three Apiaceae species Ledebouriella seseloides, Peucedanum japonicum, and Glehnia littoralis are used as Asian herbal medicines, with the confusingly similar common name "Bang-poong". We characterized the complete chloroplast (cp) genomes and 45S nuclear ribosomal DNA (45S nrDNA) sequences of two accessions for each species. The complete cp genomes of G. littoralis, L. seseloides, and P. japonicum were 147,467, 147,830, and 164,633 bp, respectively. Compared to the other species, the P. japonicum cp genome had a huge inverted repeat expansion and a segmental inversion. The 45S nrDNA cistron sequences of the three species were almost identical in size and structure. Despite the structural variation in the P. japonicum cp genome, phylogenetic analysis revealed that G. littoralis diverged 5-6 million years ago (Mya), while P. japonicum diverged from L. seseloides only 2-3 Mya. Abundant copy number variations including tandem repeats, insertion/deletions, and single nucleotide polymorphisms, were found at the interspecies level. Intraspecies-level polymorphism was also found for L. seseloides and G. littoralis. We developed nine PCR barcode markers to authenticate all three species. This study characterizes the genomic differences between L. seseloides, P. japonicum, and G. littoralis; provides a method of species identification; and sheds light on the evolutionary history of these three species.
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Apiaceae/clasificación , Apiaceae/genética , Código de Barras del ADN Taxonómico , Reordenamiento Génico , Genoma del Cloroplasto , Plantas Medicinales/clasificación , Plantas Medicinales/genética , Cloroplastos/genética , Variaciones en el Número de Copia de ADN , Genómica/métodos , Mutación , Sistemas de Lectura Abierta , Filogenia , ARN Ribosómico/genética , Análisis de Secuencia de ADN , Secuencias Repetidas en TándemRESUMEN
BACKGROUND: The ginseng (Panax ginseng C.A. Meyer) is a perennial herbaceous plant that has been used in traditional oriental medicine for thousands of years. Ginsenosides, which have significant pharmacological effects on human health, are the foremost bioactive constituents in this plant. Having realized the importance of this plant to humans, an integrated omics resource becomes indispensable to facilitate genomic research, molecular breeding and pharmacological study of this herb. DESCRIPTION: The first draft genome sequences of P. ginseng cultivar "Chunpoong" were reported recently. Here, using the draft genome, transcriptome, and functional annotation datasets of P. ginseng, we have constructed the Ginseng Genome Database http://ginsengdb.snu.ac.kr /, the first open-access platform to provide comprehensive genomic resources of P. ginseng. The current version of this database provides the most up-to-date draft genome sequence (of approximately 3000 Mbp of scaffold sequences) along with the structural and functional annotations for 59,352 genes and digital expression of genes based on transcriptome data from different tissues, growth stages and treatments. In addition, tools for visualization and the genomic data from various analyses are provided. All data in the database were manually curated and integrated within a user-friendly query page. CONCLUSION: This database provides valuable resources for a range of research fields related to P. ginseng and other species belonging to the Apiales order as well as for plant research communities in general. Ginseng genome database can be accessed at http://ginsengdb.snu.ac.kr /.
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Genoma de Planta/genética , Panax/genética , Panax/metabolismo , Bases de Datos Genéticas , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Ontología de Genes , Ginsenósidos/metabolismoRESUMEN
Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane-type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome-scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics-assisted breeding or metabolic engineering.
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Genoma de Planta/genética , Panax/genética , Adaptación Biológica/genética , Evolución Biológica , Diploidia , Genes del Cloroplasto/genética , Genes de Plantas/genética , Ginsenósidos/biosíntesis , Panax/metabolismo , TetraploidíaRESUMEN
Supercapacitors are promising energy storage devices due to their high power density, long cycling life, and short charging time. NiO is one of the alternative inorganic materials that could be used to replace the conventional RuO2 electrodes in these supercapacitors. In the present study, NiO thin film was prepared by radio frequency magnetron sputtering using a NiO alloy target. This process offeres several advantages such as the superior adhesion of the resulting thin films and the easy control of the deposition rate. Rapid thermal annealing (RTA) at different annealing temperatures was used to control the properties of the NiO thin films intended for supercapacitor applications. The lattice imperfections and interstitials/vacancies in the NiO thin films were influenced by the annealing temperature, and subsequently affected the bandgaps, optical transmittance, carrier concentration, and resistivity. Consequently, the the supercapacitive behavior was influenced by the surface area and the variation on the homogeneity of the crystallites in the NiO thin films with a change in the annealing temperature.
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STATEMENT OF PROBLEM: Rapid prototyping, including stereolithography (SLA), is a more recent technique for fabricating metal frameworks than the conventional lost-wax technique. However, investigations of the marginal discrepancies and internal spacing of cobalt-chromium (Co-Cr) metal copings fabricated using SLA are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the clinical acceptability of the marginal discrepancies and internal spacing of Co-Cr metal copings fabricated using the SLA technique. MATERIAL AND METHODS: A resin tooth of a maxillary right first premolar was prepared with a deep chamfer margin for a metal-ceramic crown. Titanium master dies were milled after scanning the prepared tooth (n=45). In conventional lost wax group (group LW), the conventional lost-wax technique was used to fabricate Co-Cr metal copings (n=15). In milling group (group MC), a computer-aided design (CAD) system was used to design the metal copings, which were milled from Co-Cr alloy (n=15). The CAD system was also used to design the metal copings in a 3D-printed group (group SL), and Co-Cr metal copings were cast from resin patterns fabricated using the SLA device (n=15). Marginal discrepancies and internal spaces were measured using an optical microscope at ×100 magnification at 11 reference points. The values were analyzed statistically with 1-way analysis of variance (α=.05). RESULTS: The mean (±SD) overall space was 63.2 ±16.6 µm for group LW, 70.2 ±15.5 µm for group SL, and 130.3 ±13.8 µm for group MC. The overall spaces differed significantly between group MC and the other 2 groups (P<.05). The marginal discrepancy and internal spaces were significantly larger in group MC than in groups LW and SL. (P<.05). Occlusal spaces differed significantly among the 3 study groups (P<.05). CONCLUSIONS: Co-Cr metal copings fabricated using an SLA technique showed clinically acceptable marginal discrepancies and internal spaces. These spaces did not differ significantly from those obtained with the conventional lost-wax technique.
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Aleaciones de Cromo/química , Diseño Asistido por Computadora , Coronas , Diseño de Prótesis Dental/métodos , Ajuste de Prótesis , Estereolitografía , Diente Premolar , Adaptación Marginal Dental , Materiales Dentales/química , Humanos , Técnicas In VitroRESUMEN
The hydrogen evolution reaction using semiconductor photocatalysts has been significantly improved by cocatalyst loading. However, there are still many speculations regarding the actual role of the cocatalyst. Now a photocatalytic hydrogen evolution reaction pathway is reported on a cocatalyst site using TiO2 nanosheets doped with Rh at Ti sites as one-atom cocatalysts. A hydride species adsorbed on the one-atom Rh dopant cocatalyst site was confirmed experimentally as the intermediate state for hydrogen evolution, which was consistent with the results of density functional theory (DFT) calculations. In this system, the role of the cocatalyst in photocatalytic hydrogen evolution is related to the withdrawal of photo-excited electrons and stabilization of the hydride intermediate species; the presence of oxygen vacancies induced by Rh facilitate the withdrawal of electrons and stabilization of the hydride.
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BACKGROUND: Expression of caveolin-1 (Cav-1) is frequently altered in many human cancers and both tumor suppression and promotion functions of Cav-1 have been suggested based on its expression status. However, it remains unanswered how Cav-1 provokes opposite effects in different cancers or different phases of tumor progression. METHODS: To explore the implication of Cav-1 alteration in gastric tumorigenesis, the expression and mutational status of Cav-1 and its effects on tumor cell growth were characterized. RESULTS: A substantial fraction of primary tumors and cell lines displayed abnormally low or high Cav-1 mRNA expression, indicating the bidirectional alteration of Cav-1 in gastric cancers. While allelic imbalance and mutational alterations of the Cav-1 gene were rarely detected, aberrant promoter hyper- or hypo-methylation showed a tight correlation with bidirectional alteration of its expression. Abnormally low and high Cav-1 expression was more frequently observed in early and advanced cancers, respectively, suggesting the oncogenic switch of its function in tumor progression. Cell cycle progression, DNA synthesis, and colony forming ability were markedly decreased by Cav-1 transfection in low-expressing tumor cells but by its depletion in high-expressing cells. Interestingly, Cav-1 exerted opposite effects on MEK-ERK signaling in these two cell types through the reciprocal regulation of the RAF-ERK negative feedback loop. A feedback inhibition of RAF by ERK was stimulated by restoration of Cav-1 expression in low-expressing cells but by it depletion in high-expressing cells. As predicted, the opposite effects of Cav-1 on both tumor cell growth and inhibitory RAF phosphorylation were abolished if ERK is depleted. CONCLUSION: Bidirectional alteration of Cav-1 is linked to its opposite effects on gastric tumor cell growth, which stem from the reciprocal control on the RAF-ERK negative feedback loop.
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Caveolina 1/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Caveolina 1/metabolismo , Metilación de ADN , Progresión de la Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Modelos Biológicos , Mutación , Polimorfismo Genético , Regiones Promotoras Genéticas , Neoplasias Gástricas/metabolismo , Quinasas raf/genética , Quinasas raf/metabolismoRESUMEN
Rational design and massive production of bifunctional catalysts with fast oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics are critical to the realization of highly efficient lithium-oxygen (Li-O2) batteries. Here, we first exploit two types of double-walled RuO2 and Mn2O3 composite fibers, i.e., (i) phase separated RuO2/Mn2O3 fiber-in-tube (RM-FIT) and (ii) multicomposite RuO2/Mn2O3 tube-in-tube (RM-TIT), by controlling ramping rate during electrospinning process. Both RM-FIT and RM-TIT exhibited excellent bifunctional electrocatalytic activities in alkaline media. The air electrodes using RM-FIT and RM-TIT showed enhanced overpotential characteristics and stable cyclability over 100 cycles in the Li-O2 cells, demonstrating high potential as efficient OER and ORR catalysts.
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This clinical report describes the management of a patient who had an excessively tight reconstructed lip because of oral cancer surgery and postoperative radiotherapy. The presented technique used an intraoral scanner for a preliminary impression and computer-aided design and computer-aided manufacturing (CAD-CAM) technology for preliminary laboratory procedures. This digital impression technique may reduce patient discomfort.