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The strength-ductility trade-off has long been a Gordian knot in conventional metallic structural materials and it is no exception in multi-principal element alloys. In particular, at ultrahigh yield strengths, plastic instability, that is, necking, happens prematurely, because of which ductility almost entirely disappears. This is due to the growing difficulty in the production and accumulation of dislocations from the very beginning of tensile deformation that renders the conventional dislocation hardening insufficient. Here we propose that premature necking can be harnessed for work hardening in a VCoNi multi-principal element alloy. Lüders banding as an initial tensile response induces the ongoing localized necking at the band front to produce both triaxial stress and strain gradient, which enables the rapid multiplication of dislocations. This leads to forest dislocation hardening, plus extra work hardening due to the interaction of dislocations with the local-chemical-order regions. The dual work hardening combines to restrain and stabilize the premature necking in reverse as well as to facilitate uniform deformation. Consequently, a superior strength-and-ductility synergy is achieved with a ductility of ~20% and yield strength of 2 GPa during room-temperature and cryogenic deformation. These findings offer an instability-control paradigm for synergistic work hardening to conquer the strength-ductility paradox at ultrahigh yield strengths.
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Nanocrystalline metals have many applications in nanodevices, especially nanoscale electronics in aerospace. Their ability to resist fracture under impact produced by environmental stress is the main concern of nanodevice design. By carrying out molecular dynamics simulations under different fast loading rates, this work examines the effect of impact load on the fracture behavior of nanocrystalline bcc iron at an atomistic scale. The results show that a crack propagates with intergranular decohesion in nanocrystalline iron. With the increase in impact load, intergranular decohesion weakens, and plastic behaviors are generated by grain boundary activities. Also, the mechanism dominating plastic deformation changes from the atomic slip at the crack tip to obvious grain boundary activities. The grain boundary activities produced by the increase in impact load lead to an increase in the threshold energy for crack cleavage and enhance nanocrystalline bcc iron resistance to fracture. Nanocrystalline bcc iron can keep a high fracture ductility under a large impact load.
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The catastrophic failure of metal/ceramic interfaces is a complex process involving the energy transfer between accumulated elastic strain energy and many types of energy dissipation. To quantify the contribution of bulk and interface cohesive energy to the interface cleavage fracture without global plastic deformation, we characterized the quasi-static fracture process of both coherent and semi-coherent fcc-metal/MgO(001) interface systems using a spring series model and molecular static simulations. Our results show that the theoretical catastrophe point and spring-back length by the spring series model are basically consistent with the simulation results of the coherent interface systems. For defect interfaces with misfit dislocations, atomistic simulations revealed an obvious interface weakening effect in terms of reduced tensile strength and work of adhesion. As the model thickness increases, the tensile failure behaviors show significant scale effects-thick models tend to catastrophic failure with abrupt stress drop and obvious spring-back phenomenon. This work provides insight into the origin of catastrophic failure at metal/ceramic interfaces, which highlights a pathway by combining the material and structure design to improve the reliability of layered metal-ceramic composites.
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The aim of this study was to explore the value of computed tomography (CT) images based on electronic health (E-health) combined with painless gastrointestinal endoscopy (PGE) in the diagnosis of neurocognitive function in patients with combined anesthesia of propofol and butorphanol tartrate. 126 patients undergoing PGE were selected as the research objects, and all were performed with CT perfusion imaging before and after anesthesia to obtain the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). The Montreal Cognitive Assessment (MoCA) was adopted to evaluate the cognitive function of patients. The results showed that after anesthesia, the levels of CBF and CBV in the left and right thalami, frontal lobe, and temporal lobe of the patients were lower than those before anesthesia, while TTP and MTT were higher than those before anesthesia (P < 0.05). The MoCA score after anesthesia was lower than that before anesthesia (P < 0.05). After anesthesia, the CBF, CBV, TTP, and MTT values of the left and right frontal lobes and left and right temporal lobes were significantly positively correlated with MoCA (P < 0.05). In conclusion, the brain CT image parameters based on E-health can clearly display the blood perfusion in the lesion area of the patient, which was beneficial to the PGE-assisted judgment of cognitive dysfunction in patients with propofol tartrate and butorphanol tartrate anesthesia. Therefore, CT-assisted PGE examination based on E-health had a certain clinical value in evaluating the neurocognitive function of patients.
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Anestesia , Propofol , Humanos , Butorfanol , Circulação Cerebrovascular , Eletrônica , Endoscopia Gastrointestinal , Propofol/efeitos adversos , Tomografia Computadorizada por Raios X/métodosRESUMO
Controlled fracture presents opportunities for the advanced fabrication of thin films. However, programmability analogous to that of Chinese paper cutting is still challenging, where fracture patterns can be created as required without preformed cracks for guidance. Here, we establish a design framework for tearing adhesive thin films from foldable substrates with such programmability. Our analytical model captures the observed crack behavior, demonstrating that the deflection of crack paths can exceed 90^{∘}. Besides, for thick foldable substrates with multiple ridges, we additionally propose a robust method of directional fracture where the cracks are forced to extend along the ridges.
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BACKGROUND: Inappropriate macrophages phenotype transition contributes to the development of ulcerative colitis, and the poly (ethylene glycol)-block-poly (d, l-lactic acid) (PEG-PLA) nanoparticles delivery system can be utilized to improve the cryptotanshinone (CTS)-based therapy. METHODS: We used a single emulsification method to prepare CTS-encapsulated nanoparticles (NPCTS). The therapeutic efficacy of NPCTS was evaluated in dextran sulfate sodium (DSS)-induced colitis mice. Then the proportion of total macrophages and M2-like macrophages were assayed with flow cytometry, and the relative content of pro-inflammatory cytokines in the colon was detected with Western blot. Bone-marrow-derived macrophages (BMDMs) were induced into M1-like macrophages, which were further incubated with NPCTS to repolarize into M2 subtype. RESULTS: Cryptotanshinone could induce the transition of M1 subtype to M2 subtype as indicated by up-regulated expression of arginase 1 (ARG1), interleukin (IL)-10, and CD206. In vivo, orally administrated NPCTS accumulated in the colon-infiltrated macrophages in colitis mice. It further revealed that NPCTS significantly alleviated colitis symptoms as indicated by increased body weight and colon length, decreased tumor necrosis factor (TNF)-α, IL-1ß, and IL-6 content in the colon, and diminished total macrophage proportion (CD45+CD11b+F4/80+) and up-regulated M2 proportion (CD45+CD11b+F4/80+CD206hi). CONCLUSION: Oral administration of NPCTS could ameliorate ulcerative colitis with the conversion of M1-like macrophages to M2-like macrophages.
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The structure of a hard film mounted on a soft viscoelastic substrate exists widely in nature and in industrial production, in which the hard film plays an important role. In this study, in order to accurately describe the indentation behaviors of hard film/soft viscoelastic substrate systems and to separate the mechanical properties of the hard film from the overall indentation response, an analytical relationship between the indentation loads and displacements was derived and presented herein based on plate theory, Hankel transformation, the elastic-viscoelastic correspondence principle, and Boltzmann superposition principle. In addition, finite element simulations and experiments were performed to investigate the effectiveness and applicability of the theoretical model. The results showed that the analytical solution agreed extremely well with the experiments and simulations. By analyzing the analytical solution, it was found that, due to the presence of the hard film, the viscous behaviors of the hard film/soft viscoelastic substrate system depended not only on the viscous properties of the soft substrate but also on the elastic properties of the soft substrate. Surprisingly, the relaxation time of the hard film/soft viscoelastic substrate system became longer than that of the soft substrate, but the ratio of the decay modulus to the equilibrium modulus was lower than that of the soft substrate. The above findings remind us that it is impossible to simply judge whether the hard film inhibits or promotes the soft substrate viscous behaviors. Our research can help readers gain insights into the indentation response characteristics of hard film/soft viscoelastic substrate systems, and it provide a theoretical basis for the measurement of the mechanical properties of a hard film mounted on a soft viscoelastic substrate.
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Long noncoding RNA (lncRNA) H19 has been suggested to serve important roles in the progression of gastric cancer (GC); however, the mechanism involved is largely unknown. The present study aimed to investigate the mechanism underlying the effect of H19 on human epidermal growth factor receptor (HER2) expression. Let7c belongs to the let7 family, which has been reported to be downregulated in cancers and considered to serve as a tumor suppressor. Let7c has been negatively associated with the expression of human epidermal growth factor receptor 2 (HER2). Reverse transcriptionquantitative polymerase chain reaction was used to examine the expression levels of H19 and let7c in GC tissues and cell lines. HER2 protein expression levels were examined using immunohistochemistry and western blot analyses. The effect of H19 on let7c and HER2 expression was analyzed following transfection of small interfering RNA targeting H19 in GC cells. The results indicated that the expression levels of H19 lncRNA in GC tissue samples were significantly higher when compared with that in matched benign adjacent tissue samples (P<0.001). H19silenced GC cells exhibited significantly increased let7c expression and decreased HER2 protein expression levels. Assessment of tumor diameter and pathological tumor stage suggested that increased H19 expression was associated with a poorer prognosis in patients with GC. The results of the present study suggest that H19 may function as a competing endogenous RNA to regulate HER2 expression by sequestering let7c in GC cells. The present study has aided the understanding of the mechanism of H19 lncRNA in GC, and has provided evidence for the application of lncRNAbased diagnostic and therapeutic strategies for GC.
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Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , RNA Interferente Pequeno , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patologia , Carga TumoralRESUMO
Monolayer two-dimensional (2D) crystals exhibit a host of intriguing properties, but the most exciting applications may come from stacking them into multilayer structures. Interlayer and interfacial shear interactions could play a crucial role in the performance and reliability of these applications, but little is known about the key parameters controlling shear deformation across the layers and interfaces between 2D materials. Herein, we report the first measurement of the interlayer shear stress of bilayer graphene based on pressurized microscale bubble loading devices. We demonstrate continuous growth of an interlayer shear zone outside the bubble edge and extract an interlayer shear stress of 40 kPa based on a membrane analysis for bilayer graphene bubbles. Meanwhile, a much higher interfacial shear stress of 1.64 MPa was determined for monolayer graphene on a silicon oxide substrate. Our results not only provide insights into the interfacial shear responses of the thinnest structures possible, but also establish an experimental method for characterizing the fundamental interlayer shear properties of the emerging 2D materials for potential applications in multilayer systems.
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The present study aimed to determine the effect of recombinant DNA vaccine-based human epidermal growth factor receptor-2 (HER2) and Interleukin 12 (IL-12) on the development of colonic carcinoma in mice and the potential immune mechanisms involved. Recombinant plasmids pVAX1-HER2, pVAX1-IL-12 and pVAX1-HER2-IL-12 were constructed, and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model with a HER2-expressing tumor was designed. Mice vaccinated with the HER2-IL-12 plasmid generated the strongest inhibition efficacy on the growth of HER2-expressing tumors and prolonged mouse survival. These observations emphasized the potential of IL-12 as an adjuvant for DNA vaccines and of vaccines based on HER2 and IL-12 as a promising treatment for colonic carcinoma.
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In this study, we report the polymer-based graphene foams through combination of bottom-up assembly and simple triaxially buckled structure design. The resulting polymer-based graphene foams not only effectively transfer the functional properties of graphene, but also exhibit novel negative Poisson's ratio (NPR) behaviors due to the presence of buckled structure. Our results show that after the introduction of buckled structure, improvement in stretchability, toughness, flexibility, energy absorbing ability, hydrophobicity, conductivity, piezoresistive sensitivity and crack resistance could be achieved simultaneously. The combination of mechanical properties, multifunctional performance and unusual deformation behavior would lead to the use of our polymer-based graphene foams for a variety of novel applications in future such as stretchable capacitors or conductors, sensors and oil/water separators and so on.
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The aim of this study is to discuss whether the methylation levels of Runx3 could be used as the early biomarker for predicting the prognosis in chronic atrophic gastritis (CAG) patients. A total of 200 subjects including 60 controls without CAG (Group 1), 70 patients with mild CAG (Group 2), and 70 patients with moderate and severe CAG (Group 3) were recruited for this cross-sectional investigation in the Department of Gastroenterology in Daqing Oilfield General Hospital from July 2013 to May 2014. The MlALDI-TOF-MS was used to measure the methylation levels of Runx3 in all of the subjects. Real-time quantitative reverse transcription polymerase chain reaction and western blotting were chosen to determine the expression levels of Runx3. The correlations between methylation levels of Runx3 among these CAG patients and their prognosis were shown by logistic regression models. The results demonstrated that the methylation levels of CpG13, CpG14, and CpG15 in Runx3 were higher in Group 3 than those in Groups 1 and 2 (Pâ<0.05), whereas the mRNA and protein expression levels of Runx3 were lower in Group 3 than those in Groups 1 and 2 (Pâ<0.05). There were significantly negative correlations between the methylation levels of Runx3 with its expression and the healing prognosis of CAG patients. In brief, this study proved that the hypermethylation modifications of CpG13, CpG14, and CpG15 in the promoter region of Runx3 could result in the down regulation of Runx3 expression to affect the prognosis of CAG. So the methylation levels of these CpG sites in Runx3 in the peripheral blood can be used as the biomarker for predicting the healing prognosis of CAG patients.
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Subunidade alfa 3 de Fator de Ligação ao Core/genética , Ilhas de CpG/genética , Metilação de DNA , Gastrite Atrófica/genética , RNA Mensageiro/sangue , Adulto , Biomarcadores , Estudos de Casos e Controles , Doença Crônica , Subunidade alfa 3 de Fator de Ligação ao Core/sangue , Estudos Transversais , Feminino , Gastrite Atrófica/patologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de DoençaRESUMO
Efficient assembly of carbon nanotube (CNT) based cellular solids with appropriate structure is the key to fully realize the potential of individual nanotubes in macroscopic architecture. In this work, the macroscopic CNT sponge consisting of randomly interconnected individual carbon nanotubes was grown by CVD, exhibiting a combination of super-elasticity, high strength to weight ratio, fatigue resistance, thermo-mechanical stability and electro-mechanical stability. To deeply understand such extraordinary mechanical performance compared to that of conventional cellular materials and other nanostructured cellular architectures, a thorough study on the response of this CNT-based spongy structure to compression is conducted based on classic elastic theory. The strong inter-tube bonding between neighboring nanotubes is examined, believed to play a critical role in the reversible deformation such as bending and buckling without structural collapse under compression. Based on in-situ scanning electron microscopy observation and nanotube deformation analysis, structural evolution (completely elastic bending-buckling transition) of the carbon nanotubes sponges to deformation is proposed to clarify their mechanical properties and nonlinear electromechanical coupling behavior.
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Conventional metals are routinely hardened by grain refinement or by cold working with the expense of their ductility. Recent nanostructuring strategies have attempted to evade this strength versus ductility trade-off, but the paradox persists. It has never been possible to combine the strength reachable in nanocrystalline metals with the large uniform tensile elongation characteristic of coarse-grained metals. Here a defect engineering strategy on the nanoscale is architected to approach this ultimate combination. For Nickel, spread-out nanoscale domains (average 7 nm in diameter) were produced during electrodeposition, occupying only ~2.4% of the total volume. Yet the resulting Ni achieves a yield strength approaching 1.3 GPa, on par with the strength for nanocrystalline Ni with uniform grains. Simultaneously, the material exhibits a uniform elongation as large as ~30%, at the same level of ductile face-centered-cubic metals. Electron microscopy observations and molecular dynamics simulations demonstrate that the nanoscale domains effectively block dislocations, akin to the role of precipitates for Orowan hardening. In the meantime, the abundant domain boundaries provide dislocation sources and trapping sites of running dislocations for dislocation multiplication, and the ample space in the grain interior allows dislocation storage; a pronounced strain-hardening rate is therefore sustained to enable large uniform elongation.