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For decreasing the global cost of corrosion, it is essential to understand the intricate mechanisms of corrosion and enhance the corrosion resistance of materials. However, the ambiguity surrounding the dominant mechanism of calcium-magnesium aluminosilicate (CMAS) molten salt corrosion in extreme environments hinders the mix-and-matching of the key rare earth elements for increasing the resistance of monosilicates against corrosion of CMAS. Herein, an approach based on correlated electron microscopy techniques combined with density functional theory calculations is presented to elucidate the complex interplay of competing mechanisms that control the corrosion of CMAS of monosilicates. These findings reveal a competition between thermodynamics and kinetics that relies on the temperatures and corrosion processes. Innovative medium-entropy monosilicates with exceptional corrosion resistance even at 1500 °C are developed. This is achieved by precisely modulating the radii of rare earth ions in monosilicates to strike a delicate balance between the competition in thermodynamics and kinetics. After 50 and 100 h of corrosion, the thinnest reactive layers are measured to be only 28.8 and 35.4 µm, respectively.
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Behaviour is rooted in the organization and activity of an animal's nervous system. As male crickets use their front wings for sound production, the neural circuits underlying singing had been suggested to be housed in the thoracic ganglia. However, systematic lesion experiments of the CNS demonstrated that the abdominal nervous system is essential for their calling song behaviour. As male crickets also generate a courtship and rivalry song, we explored which parts of the abdominal central nervous system control the underlying motor patterns. A combination of systematic lesions to the abdominal nerve cord and video recording of courtship and rivalry behaviour revealed that most components of male courtship and rivalry behaviour were not affected by the lesions, except for the generation of courtship song, rivalry song, and the male's ability to copulate with the female. Any lesion to the abdominal nerve cord abolished copulations. Generation of courtship song initially failed when the connection to abdominal ganglion A6 was severed but in few males recovered after a week. For rivalry song production a central nerve cord extending to abdominal ganglion A4 was sufficient. These findings indicate that in the bispotted cricket the neural organization of courtship song is different from calling and rivalry song, while calling song and rivalry song might share a common network for generating the song patterns.
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Gryllidae , Animales , Copulación , Cortejo , Femenino , Masculino , Conducta Sexual Animal , Vocalización Animal , Alas de AnimalesRESUMEN
The purpose of this work was to fabricate and characterize Ca doped wrinkled porous silica (Ca-WPS), and evaluate their effect on the mineralization and mechanical properties of resin composites as functional fillers. Ca-WPS were prepared by sol-gel method and characterized by scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption measurements. The mineralization properties of the prepared Ca-WPS particles and the resin composites with different amount of Ca-WPS were evaluated by simulated body fluid (SBF) immersion method. The mechanical properties (flexural strength, flexural modulus, compressive strength and microhardness) of the dental resins containing unimodal Ca-WPS fillers and bimodal Ca-WPS fillers with nonporous silica were evaluated by a universal testing machine. Results showed that after immersing in SBF for 5 d, apatite formed on the surface of Ca-WPS and composites containing Ca-WPS fillers, indicating the excellent mineralization property of the prepared Ca-WPS. The mechanical properties of the dental resins increase with the increase of the proportion of unimodal Ca-WPS fillers. The dental resins with bimodal Ca-WPS fillers showed better mechanical properties than the group with only nonporous fillers at the same filler loading (60 wt%). Among all the samples, the dental composites filled with bimodal fillers (mass ratio of Ca-WPS: nonporous silica = 10:50, total filler loading 60 wt%) exhibited the best mechanical performance. The flexural strength, flexural modulus, compressive strength and microhardness of these samples were 26.96%, 42.75%, 16.04% and 54.1% higher than the composites with solid silica particles alone, respectively. Thus, the prepared Ca-WPS could effectively improve the apatite formation and mechanical properties of resin composites.
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Apatitas , Dióxido de Silicio , Resinas Compuestas , Ensayo de Materiales , Porosidad , Propiedades de SuperficieRESUMEN
We recorded the wing movements and sound signals during the production of calling, rivalry, and courtship song in the bispotted field cricket Gryllus bimaculatus. Recordings confirm that salient sound pulses during calling and rivalry song are generated during the closing movements of the wings. Wing movements for calling and rivalry song start from an elevated wing position and are performed with a very similar opening-closing movement, indicating that both types of songs may be generated by the same neuronal network. Wing movements for courtship song start from a low wing position; rapid closing movements generate high-frequency ticks and low-amplitude wing oscillations lead to low-amplitude pulses, generated during the opening and closing movements with a carrier frequency corresponding to the calling song. The two types of wing movements underlying courtship song indicate a different motor control as compared to calling song and may represent an early evolutionary phenotype.
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Gryllidae/fisiología , Movimiento/fisiología , Conducta Sexual Animal/fisiología , Vocalización Animal/fisiología , Animales , Evolución Biológica , Masculino , Técnicas Fotoacústicas/métodos , Alas de Animales/fisiologíaRESUMEN
Although crickets move their front wings for sound production, the abdominal ganglia house the network of the singing central pattern generator. We compared the effects of specific lesions to the connectives of the abdominal ganglion chain on calling song activity in four different species of crickets, generating very different pulse patterns in their calling songs. In all species, singing activity was abolished after the connectives between the metathoracic ganglion complex and the first abdominal ganglion A3 were severed. The song structure was lost and males generated only single sound pulses when connectives between A3 and A4 were cut. Severing connectives between A4 and A5 had no effect in the trilling species, it led to an extension of chirps in a chirping species and to a loss of the phrase structure in two Teleogryllus species. Cutting the connectives between A5 and A6 caused no or minor changes in singing activity. In spite of the species-specific pulse patterns of calling songs, our data indicate a conserved organisation of the calling song motor pattern generating network. The generation of pulses is controlled by ganglia A3 and A4 while A4 and A5 provide the timing information for the chirp and/or phrase structure of the song.
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Generadores de Patrones Centrales/fisiología , Ganglios de Invertebrados/fisiología , Gryllidae/fisiología , Vocalización Animal/fisiología , Animales , MasculinoRESUMEN
OBJECTIVE: The purpose of this work was to explore the enhancement effect of zinc doped mesoporous silica nanoparticles (Zn-MSNs), which could form micromechanical interlocking with resin matrix and sustainably release Zn2+, on the mechanical and antibacterial properties of the dental resin composites. METHODS: Zn-MSNs were prepared by a sol-gel method, and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and N2 adsorption/desorption. The mechanical properties of the dental composites reinforced by Zn-MSNs were measured by a universal mechanical testing machine. Antibacterial activities of dental composites were evaluated by both qualitative and quantitative analysis using Streptococcus mutans (S. mutans). The cytotoxicity of the Zn-MSNs filled dental composites was investigated by osteoblasts (OBs). RESULTS: The synthesized Zn-MSNs possessed good monodispersity with an average particle size of about 138nm. The mechanical properties of the composites gradually increased with the increase of the content of Zn-MSNs. The flexural strength, flexural modulus, compressive strength and micro-hardness of the composites containing 15wt% Zn-MSNs were 31.21%, 50.47%, 53.83% and 26.79% higher than the samples with no Zn-MSNs, respectively. The antibacterial performance was significantly improved by the addition of Zn-MSNs and the antibacterial rate of the composite with 15wt% of Zn-MSNs reached 100%. Cytotoxicity tests revealed that all the composites were biocompatible during OBs incubation. SIGNIFICANCE: The prepared Zn-MSNs can effectively improve the mechanical and antibacterial properties of the dental resin composites.
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Nanopartículas , Dióxido de Silicio , Antibacterianos/farmacología , Resinas Compuestas , Ensayo de Materiales , Docilidad , Propiedades de Superficie , ZincRESUMEN
Electron backscatter diffraction (EBSD) device can provide crystal structure, orientation, and phase content data through analysis of EBSD patterns. The reliability and precision of these data depend on the quality of the band position and zone axes data. This study introduces a new image processing method that can accurately provide the location of Kikuchi bands and poles. In this method, pattern rotation and gray gradient calculation are employed after for the initial detection of Kikuchi lines. Hough transform and Gaussian function are used for the final definition of bands position. Based on the position of Kikuchi bands, the indices of lattice planes and zone axes can be obtained precisely and easily. Angles between zone axes are calculated using locating results. The maximum error for a single-crystal silicon sample is only 8.07%, illustrating the accuracy of this new method.
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Enhancing the properties of thermal barrier coatings (TBCs) by doping with rare earth elements has been a hot topic for a while. La2O3 and Y2O3 co-doped ZrO2 (La-YSZ) TBCs and yttria-stabilized zirconia (YSZ) TBCs were deposited by atmospheric plasma spraying (APS), and the comprehensive effects of La3+ on the microstructure and property were investigated. The thermal conductivity and microstructure were investigated and were compared with YSZ. The recrystallized fraction components of all TBCs were quantified. It is clearly found that the component of "recrystallized" and "deformed" grains for La-YSZ TBCs is much higher than that for YSZ TBCs. This could be due to La3+ doping enlarging the lattice parameter of YSZ and thus increasing the melting index, which in turns leads to the smaller grain size of La-YSZ TBCs. As a result, the thermal conductivities of La-YSZ TBCs were distinctly lower than those of YSZ TBCs.
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Surface modifications play an important role in endowing implant surface with excellent biocompatibility and bioactivity. Among the bioinspired surface modifications, the mussel-inspired polydopamine (PDA) has aroused great interest of researchers. Herein, we fabricated PDA on diverse implant surfaces, including biopolymer, biometal, and bioceramic. Then the effects of PDA coating on cell responsive behaviors in vitro and bone formation capacity in vivo were evaluated in detail. The results showed that PDA coating was fabricated on diverse samples surface successfully, which could significantly improve the hydrophilicity of different material surfaces. Furthermore, the results indicated that PDA coating exerted direct enhancing on the adhesion, proliferation and osteogenic differentiation of bone marrow derived mesenchymal stromal cells (BMSCs) through FAK and p38 signaling pathways. During the process, the focal adhesion protein expression and osteogenic-related genes expression level (e.g., ALP, BMP2, BSP, and OPN) were considerably upregulated. Most importantly, the in vivo study confirmed that PDA coating remarkably accelerated new bone formation and enhanced osseointegration performance. Our study uncovered the biological responses stimulated by PDA coating to make a better understanding of cell/tissue-PDA interactions and affirmed that PDA, a bioinspired polymer, has great potential as a candidate and functional bioactive coating medium in bone regeneration and orthopedic application.
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Bivalvos , Materiales Biocompatibles Revestidos , Implantes Experimentales , Indoles , Oseointegración/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Polímeros , Animales , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Indoles/química , Indoles/farmacología , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Polímeros/química , Polímeros/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND/AIMS: Hyperglycemia has been shown to increase the incidence and metastasis in various types of cancers. However, the correlation between hyperglycemia and lymphatic metastasis in prostate cancer (PCa) remains unclear. Our previous study demonstrated that lysophosphatidic acid (LPA) enhances vascular endothelial growth factor-C (VEGF-C) expression, a lymphangiogenic factor, through activating it receptors LPA1/3 in prostate cancer (PCa) cells. Moreover, hyperglycemia up-regulates autotaxin (ATX) expression, a LPA-generating enzyme. Therefore, we propose that high glucose promotes VEGF-C expression through LPA signaling in PCa cells. METHODS: Pharmacological inhibitors and siRNAs were utilized to investigate the molecular mechanism of high glucose-induced VEGF-C expression. Real-time PCR and Western blot were used to determine the mRNA and protein expressions, respectively. Cellular bioenergetics analysis was performed to determine the glycolysis levels. RESULTS: We demonstrated that the expressions of VEGF-C, ATX, and calreticulin were increased upon high glucose treatments in PC-3 cells. Moreover, high glucose-induced VEGF-C expression was mediated through the LPA1/3, PLC, Akt, ROS and LEDGF-dependent pathways. Additionally, high glucose enhanced the aerobic glycolysis via LPA1/3. CONCLUSION: These results indicated that hyperglycemia leads to LPA synthesis, and subsequent promoting pathological consequence of PCa. These novel findings could potentially provide new strategies for PCa treatments.
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Glucosa/farmacología , Transducción de Señal/efectos de los fármacos , Factor C de Crecimiento Endotelial Vascular/metabolismo , Calreticulina/antagonistas & inhibidores , Calreticulina/genética , Calreticulina/metabolismo , Línea Celular Tumoral , Glucólisis , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Lisofosfolípidos/metabolismo , Masculino , Consumo de Oxígeno/efectos de los fármacos , Fosfoinositido Fosfolipasa C/genética , Fosfoinositido Fosfolipasa C/metabolismo , Hidrolasas Diéster Fosfóricas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Receptores del Ácido Lisofosfatídico/genética , Receptores del Ácido Lisofosfatídico/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Factor C de Crecimiento Endotelial Vascular/genéticaRESUMEN
A major challenge when performing scanning electron microscopy and X-ray analysis on many ceramic materials is their electrical insulation properties, which leads to buildup of the surface charge and reduced contrast in the secondary electron image. A new procedure was established to quantitatively determine the neutral state values, E1 and E2 , of yttrium aluminum garnet (YAG) ceramics using the Duane-Hunt limit (EDHL ) of Bremsstrahlung, in order to eliminate this charge effect. Thirty-eight EDHL values were linearly fitted with the last portion of X-ray spectra acquired under the incident energy, E0 , from 0.35 to 5.0 kV. According to the distribution of EDHL , two piecewise linear fitting was first employed with a breakpoint of 1.0 kV. Consequently, two intersection points of 0.54 and 2.48 kV, which correspond to E1 and E2 for YAG ceramics, were directly determined using a theoretical curve (EDHL = E0 ). As a result, the high-resolution images of the YAG ceramic grain structure were successfully obtained using the calculated E1 and E2 values.
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Recent years have witnessed a breathtaking development of wearable strain sensors. Coupling high sensitivity and stretchability in a strain sensor is greatly desired by emerging wearable applications but remains a big challenge. To tackle this issue, a through-layer buckle wavelength-gradient design is proposed and a facile and universal fabrication strategy is demonstrated to introduce such a gradient into the sensing film with multilayered sensing units. Following this strategy, strain sensors are fabricated using graphene woven fabrics (GWFs) as sensing units, which exhibit highly tunable electromechanical performances. Specifically, the sensor with 10-layer GWFs has a gauge factor (GF) of 2996 at a maximum strain of 242.74% and an average GF of 327. It also exhibits an extremely low minimum detection limit of 0.02% strain, a fast signal response of less than 90 ms, and a high cyclic durability through more than 10 000 cycling test. Such excellent performances qualify it in accurately monitoring full-range human activities, ranging from subtle stimuli (e.g., pulse, respiration, and voice recognition) to vigorous motions (finger bending, walking, jogging, and jumping). The combination of experimental observations and modeling study shows that the predesigned through-layer buckle wavelength gradient leads to a layer-by-layer crack propagation process, which accounts for the underlying working mechanism. Modeling study shows a great potential for further improvement of sensing performances by adjusting fabrication parameters such as layers of sensing units ( n) and step pre-strain (εsp). For one thing, when εsp is fixed, the maximum sensing strain could be adjusted from >240% ( n = 10) to >450% ( n = 15) and >1200% ( n = 20). For the other, when n is fixed, the maximum sensing strain could be adjusted from >240% (εsp = 13.2%) to >400% (εsp = 18%) and >800% (εsp = 25%).
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Both the topographic surface and chemical composition modification can enhance rapid osteogenic differentiation and bone formation. Till now, the synergetic effects of topography and chemistry cues guiding biological responses have been rarely reported. Herein, the ordered micro-patterned topography and classically essential trace element of strontium (Sr) ion doping were selected to imitate topography and chemistry cues, respectively. The ordered micro-patterned topography on Sr ion-doped bioceramics was successfully duplicated using the nylon sieve as the template. Biological response results revealed that the micro-patterned topography design or Sr doping could promote cell attachment, ALP activity, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Most importantly, the samples both with micro-patterned topography and Sr doping showed the highest promotion effects, and could synergistically activate the ERK1/2 and p38 MAPK signaling pathways. The results suggested that the grafts with both specific topography and chemistry cues have synergetic effects on osteogenic activity of BMSCs and provide an effective approach to design functional bone grafts and cell culture substrates.
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Células de la Médula Ósea/citología , Diferenciación Celular , Sistema de Señalización de MAP Quinasas , Células Madre Mesenquimatosas/citología , Osteogénesis , Andamios del Tejido/química , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Adhesión Celular , Células Cultivadas , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Nylons/química , Ratas , Ratas Sprague-Dawley , Estroncio/química , Estroncio/farmacología , Propiedades de Superficie , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Optimal balance between biological activity and mechanical stability should be meticulously considered during scaffold design for bone tissue engineering applications. To fabricate an individualized construct with biomechanical and biological functionality for bone tissue regeneration, a polycaprolactone-collagen (PCL-COL) composite construct was developed through the combination of three-dimensional printing (3-DP) technology and biomimetic collagen matrix incorporation, with a 3-DP PCL framework maintaining the mechanical stability and a porous collagen matrix improving the biological activity. The results indicate that the compressive modulus of the composite constructs increased synergistically (over 40 MPa), providing sufficient mechanical support during new bone formation. On the other hand, the collagen matrix with a micro-porous architecture structurally increased scaffold areas and provided cellular adhesion sites, allowing for the functional construction of a favorable 3D microenvironment for BMSC adhesion, proliferation and extracellular matrix production. Moreover, critical-sized long bone defect (CSD) implantation demonstrated that the optimized composite constructs could promote bone tissue regeneration (5.5-fold) and bone-material osteointegration (4.7-fold), and decrease fibrosis encapsulation, compared to pristine PCL. The results indicate that these biomimetically ornamented PCL-COL constructs exhibit favorable mechanical properties and biological functionality, demonstrating great potential as an effective bone graft substitute for bone defect treatment. Meanwhile, they can also harness the advantages of 3-DP technology and a collagen-based functionalized strategy, facilitating the creation of customized and functional PCL-COL constructs for clinical translation.
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Our previous studies suggest that the fully active form of Peptidylarginine deiminase 4 (PAD4) should be a dimer and not a monomer. This paper provides a plausible mechanism for the control of PAD4 catalysis by molecular interplay between its dimer-interface loop (I-loop) and its substrate-binding loop (S-loop). Mutagenesis studies revealed that two hydrophobic residues, W347 and V469, are critical for substrate binding at the active site; mutating these two residues led to a severe reduction in the catalytic activity. We also identified several hydrophobic amino acid residues (L6, L279 and V283) at the dimer interface. Ultracentrifugation analysis revealed that interruption of the hydrophobicity of this region decreases dimer formation and, consequently, enzyme activity. Molecular dynamic simulations and mutagenesis studies suggested that the dimer interface and the substrate-binding site of PAD4, which consist of the I-loop and the S-loop, respectively, are responsible for substrate binding and dimer stabilization. We identified five residues with crucial roles in PAD4 catalysis and dimerization: Y435 and R441 in the I-loop, D465 and V469 in the S-loop, and W548, which stabilizes the I-loop via van der Waals interactions with C434 and Y435. The molecular interplay between the S-loop and the I-loop is crucial for PAD4 catalysis.
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Histonas/química , Multimerización de Proteína , Desiminasas de la Arginina Proteica/química , Biocatálisis , Dominio Catalítico , Clonación Molecular , Cristalografía por Rayos X , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Histonas/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Simulación de Dinámica Molecular , Mutación , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Arginina Deiminasa Proteína-Tipo 4 , Desiminasas de la Arginina Proteica/genética , Desiminasas de la Arginina Proteica/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidad por SustratoRESUMEN
Hierarchically structured zeolites (HSZs) have gained much academic and industrial interest owing to their multiscale pore structures and consequent excellent performances in varied chemical processes. Although a number of synthetic strategies have been developed in recent years, the scalable production of HSZs single crystals with penetrating and three-dimensionally (3-D) interconnected mesopore systems but without using a mesoscale template is still a great challenge. Herein, based on a steam-assisted crystallization (SAC) method, we report a facile and scalable strategy for the synthesis of single-crystalline ZSM-5 HSZs by using only a small amount of micropore-structure-directing agents (i.e., tetrapropylammonium hydroxide). The synthesized materials exhibited high crystallinity, a large specific surface area of 468â m(2) g(-1) , and a pore volume of 0.43â cm(3) g(-1) without sacrificing the microporosity (≈0.11â cm(3) g(-1) ) in a product batch up to 11.7â g. Further, a kinetically controlled nucleation-growth mechanism is proposed for the successful synthesis of single-crystalline ZSM-5 HSZs with this novel process. As expected, compared with the conventional microporous ZSM-5 and amorphous mesoporous Al-MCM-41 counterparts, the synthesized HSZs exhibited significantly enhanced activity and stability and prolonged lifetime in model reactions, especially when bulky molecules were involved.
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Bioceramics play an important role in bone regeneration. However, it is challenging to design bioceramic scaffolds with suitable ionic components and beneficial osteo/angio-stimulation ability for enhanced bone regeneration. In this study, we successfully synthesized a pure-phase Sr5(PO4)2SiO4 (SPS) bioactive ceramic through a solid-state reaction method and further prepared highly uniform SPS bioceramic scaffolds with controlled macropore sizes and mechanical strength by a 3D-plotting technique, and the biological responses of rabbit bone marrow stromal cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) after culturing with different concentrations of SPS extracts and porous scaffolds were systematically studied. The results showed that the ionic products from SPS bioceramics significantly stimulated the proliferation, alkaline phosphate (ALP) activity and osteogenesis-related gene expression (Runx2, ALP, OCN, OPN) of rBMSCs as well as the proliferation and angiogenesis-related gene expression (VEGF, KDR, eNOS, HIF 1α) of HUVECs. 3D-plotted SPS scaffolds could effectively support the attachment and proliferation of both rBMSCs and HUVECs, and the proliferation rates of the two kinds of cells in SPS scaffolds were distinctively higher than those in ß-tricalcium phosphate (ß-TCP) scaffolds prepared by the same method. In addition, the compressive strength of SPS scaffolds could be well controlled in the range 8-30 MPa when their pore size varied from 100 to 300 µm, which was significantly higher than those of ß-TCP scaffolds with similar pore sizes (â¼1.5 times). Our results demonstrated that 3D-plotted SPS bioceramic scaffolds with such a specific ionic combination and high mechanical strength as well as good degradability possessed the ability to stimulate both osteogenic and angiogenic differentiation of tissue cells, indicating that they might be promising biomaterials for bone tissue engineering.
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Erythrocytes and megakaryocytes (MK) are derived from a common progenitor that undergoes lineage specification. Lysophosphatidic acid (LPA), a lipid growth factor was previously shown to be a regulator for erythropoietic process through activating LPA receptor 3 (LPA3). However, whether LPA affects megakaryopoiesis remains unclear. In this study, we used K562 leukemia cell line as a model to investigate the roles of LPA in MK differentiation. We demonstrated that K562 cells express both LPA2 and LPA3, and the expression levels of LPA2 are higher than LPA3. Treatment with phorbol 12-myristate 13-acetate, a commonly used inducer of megakaryopoiesis, reciprocally regulates the expressions of LPA2 and LPA3. By pharmacological blockers and knockdown experiments, we showed that activation of LPA2 suppresses whereas, LPA3 promotes megakaryocytic differentiation in K562. The LPA2-mediated inhibition is dependent on ß-catenin translocation, whereas reactive oxygen species (ROS) generation is a downstream signal for activation of LPA3. Furthermore, the hematopoietic transcriptional factors GATA-1 and FLI-1, appear to be involved in these regulatory mechanisms. Taken together, our results suggested that LPA2 and LPA3 may function as a molecular switch and play opposing roles during megakaryopoiesis of K562 cells.
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Leucemia Eritroblástica Aguda/metabolismo , Megacariocitos/metabolismo , Receptores del Ácido Lisofosfatídico/metabolismo , Trombopoyesis , Factor de Transcripción GATA1/metabolismo , Humanos , Integrina beta3/metabolismo , Células K562 , Leucemia Eritroblástica Aguda/genética , Megacariocitos/efectos de los fármacos , Proteínas de Microfilamentos/metabolismo , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Receptores del Ácido Lisofosfatídico/genética , Transducción de Señal , Acetato de Tetradecanoilforbol/farmacología , Trombopoyesis/efectos de los fármacos , Factores de Tiempo , Transactivadores , Transfección , beta Catenina/metabolismoRESUMEN
A novel solvothermal-induced self-assembly approach, using colloid sol as precursor, is developed to construct monolithic 3D metal oxide/GS (graphene sheets) aerogels. During the solvothermal process, graphene oxide (GO) is highly reduced to GS and self-assembles into 3D macroscopic hydrogels, accompanying with in situ transformation of colloid sol to metal oxides. As a proof of concept, Fe2 O3 /GS aerogels are synthesized based on Fe(OH)3 sol, in which GS self-assemble into an interconnected macroporous framework and Fe2 O3 nanocrystals (20-50 nm) uniformly deposit on GS. Benefitting from the integration of macroporous structures, large surface area, high electrical conductivity, and good electrode homogeneity, the hybrid electrode manifests a superior rate capability (930, 660 and 520 mAh g(-1) at 500, 2000 and 4000 mA g(-1), respectively) and excellent prolonged cycling stability at high rates (733 mAh g(-1) during 1000 charge/discharge cycles at 2000 mA g(-1)), demonstrating its great potential for application in high performance lithium ion batteries. The work described here provides a versatile pathway to construct various graphene-based hybrid aerogels.
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Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA1 and LPA3 siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.