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Multilayer coatings offer significant advantages in protecting materials' surfaces by shielding the underlying materials hierarchically from damage and wear. The layering morphology and structure of multilayer coatings directly affect their wear resistance capacity. Using a systematic set of experiments and molecular dynamics (MD) simulations, we studied the effect of layering thickness on the macroscale wear response of DLC/WC multinanolayer coatings. Our study revealed the existence of a critical bilayer thickness where maximum scratch hardness and wear resistance can be achieved. Our large-scale MD simulations showed that reducing the WC layer thickness to a certain limit increases the scratch hardness due to the confinement of dislocation motion. However, when the thickness of the WC layers falls below 2 nm, the deformation mechanism transitions from the interface-induced dislocation confinement to the interface-mediated amorphization of WC layers, reducing the scratch hardness of the coating. This finding offers a procedure for optimizing the macroscale wear performance of multinanolayer coatings.
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Physical activity has been considered an important non-medication intervention in preserving mnemonic processes during aging. However, how aerobic exercise promotes such benefits for human health remains unclear. In this study, we aimed to explore the neuroprotective and anti-inflammatory effects of aerobic exercise against lipopolysaccharide (LPS)-induced amnesic C57BL/6J mice and BV-2 microglial cell models. In the in vivo experiment, the aerobic exercise training groups were allowed to run on a motorized treadmill 5 days/week for 4 weeks at a speed of 10 rpm/min, with LPS (0.1 mg/kg) intraperitoneally injected once a week for 4 weeks. We found that aerobic exercise ameliorated memory impairment and cognitive deficits among the amnesic mice. Correspondingly, aerobic exercise significantly increased the protein expressions of FNDC5, which activates target neuroprotective markers BDNF and CREB, and antioxidant markers Nrf2/HO-1, leading to inhibiting microglial-mediated neuroinflammation and reduced the expression of BACE-1 in the hippocampus and cerebral cortex of amnesic mice. We estimated that aerobic exercise inhibited neuroinflammation in part through the action of FNDC5/irisin on microglial cells. Therefore, we explored the anti-inflammatory effects of irisin on LPS-stimulated BV-2 microglial cells. In the in vitro experiment, irisin treatment blocked NF-κB/MAPK/IRF3 signaling activation concomitantly with the significantly lowered levels of the LPS-induced iNOS and COX-2 elevations and promotes the Nrf2/HO-1 expression in the LPS-stimulated BV-2 microglial cells. Together, our findings suggest that aerobic exercise can improve the spatial learning ability and cognitive functions of LPS-treated mice by inhibiting microglia-mediated neuroinflammation through its effect on the expression of BDNF/FNDC5/irisin.
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Disfunción Cognitiva , Lipopolisacáridos , Ratones , Humanos , Animales , Lipopolisacáridos/efectos adversos , Enfermedades Neuroinflamatorias , Fibronectinas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratones Endogámicos C57BL , Disfunción Cognitiva/terapia , Disfunción Cognitiva/tratamiento farmacológico , Estrés Oxidativo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , FN-kappa B/metabolismo , Inflamación/terapia , Inflamación/tratamiento farmacológicoRESUMEN
The tribological properties and preosteoblast behavior of an RF magnetron-sputtered amorphous carbon coating on a Si (100) substrate were evaluated. The graphite target power was varied from 200 to 500 W to obtain various coating structures. The amorphous nature of the coatings was confirmed via Raman analysis. The contact angle also increased from 58º to 103º, which confirmed the transformation of the a-C surface from a hydrophilic to hydrophobic nature with an increasing graphite target power. A minimum wear rate of about 4.73 × 10-8 mm3/N*mm was obtained for an a-C coating deposited at a 300 W target power. The 300 W and 400 W target power coatings possessed good tribological properties, and the 500 W coating possessed better cell viability and adhesion on the substrate. The results suggest that the microstructure, wettability, tribological behavior and biocompatibility of the a-C coating were highly dependent on the target power of the graphite. A Finite Element Analysis (FEA) showed a considerable increase in the Von Mises stress as the mesh size decreased. Considering both the cell viability and tribological properties, the 400 W target power coating was identified to have the best tribological property as well as biocompatibility.
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Poly(methyl methacrylate) (PMMA)-based denture base resins easily develop oral bacterial and fungal biofilms, which may constitute a significant health risk. Conventional bacterial-resistant additives and coatings often cause undesirable changes in the resin. Reduced bacterial resistance over time in the harsh oral environment is a major challenge in resin development. Poly(2-methoxyethyl acrylate) (PMEA) has anti-fouling properties; however, due to the oily/rubbery state of this polymer, and its surface aggregation tendency in a resin mixture, its direct use as a resin additive is limited. This study aimed to optimize the use of PMEA in dental resins. Acrylic resins containing a series of PMEA polymers with various molecular weights (MWs) at different concentrations were prepared, and the mechanical properties, surface gloss, direct transmittance, and cytotoxicity were evaluated, along with the distribution of PMEA in the resin. Resins with low-MW PMEA (2000 g mol-1) (PMEA-1) at low concentrations satisfied the clinical requirements for denture resins, and the PMEA was homogeneously distributed. The anti-fouling performance of the resin was evaluated for protein adsorption, bacterial and fungal attachment, and saliva-derived biofilm formation. The PMEA-1 resin most effectively inhibited biofilm formation (â¼50% reduction in biofilm mass and thickness compared to those of the control). Post-aged resins maintained their mechanical properties and anti-fouling activity, and polished surfaces had the same anti-biofilm behavior. Based on wettability and tribological results, we propose that the PMEA additive creates a non-stick surface to inhibit biofilm formation. This study demonstrated that PMEA additives can provide a stable and biocompatible anti-fouling surface, without sacrificing the mechanical properties and aesthetics of denture resins.
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Incrustaciones Biológicas , Bases para Dentadura , Acrilatos , Incrustaciones Biológicas/prevención & control , Bases para Dentadura/microbiología , Ensayo de Materiales , Peso Molecular , Polímeros , Polimetil Metacrilato , Propiedades de SuperficieRESUMEN
Notwithstanding the success of nanolayered coatings in the reduction of wear at nano-/microscales, the improvement of the wear resistance at the macroscale remains an issue. Moreover, the effects of nanointerfaces in nanolayered coatings on their macrotribological properties are not understood well. This paper reports on the engineering of nanointerfaces in diamond-like C/Cr nanolayered coatings to tailor their characteristics including the degree of intermixing, defects, and Cr growth mode. The result was the fabrication of a coating with subnanometer-thick periodic albeit discrete Cr interlayers. This was achieved using our patented deposition technique. This coating contained less interfacial defects compared to classic nanolayered coatings with continuous nanolayers and presented record-breaking wear rates at the macroscale. Finite Element analysis was performed and micropatterning strategy was used to reduce the wear rate further. Last, we report on discovery of a dimensionless parameter that can be used to predict the wear resistance of carbon-based nanolayered coatings.
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Collective cell migration plays a critical role in physiological and pathological processes such as development, wound healing, and metastasis. Numerous studies have demonstrated how various types of chemical, mechanical, and electrical cues dictate the collective migratory behaviors of cells. Although an acoustic cue can be advantageous because of its noninvasiveness and biocompatibility, cell migration in response to acoustic stimulation remains poorly understood. In this study, we developed a device that is able to apply surface acoustic waves to a cell culture substrate and investigated the effect of propagating acoustic waves on collective cell migration. The migration distance estimated at various wave intensities revealed that unidirectional cell migration was enhanced at a critical wave intensity and that it was suppressed as the intensity was further increased. The increased migration might be attributable to cell orientation alignment along the direction of the propagating wave, as characterized by nucleus shape. Thicker actin bundles indicative of a high traction force were observed in cells subjected to propagating acoustic waves at the critical intensity. Our device and technique can be useful for regulating cellular functions associated with cell migration.
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We investigated the tribological behavior of commercialized, fully synthetic engine oil upon the incorporation of reduced graphene oxide in seven different concentrations between 0.01 and 0.2 wt %. Stability of the prepared samples was assessed by turbidimetry and dynamic light scattering measurements, and their tribological properties through a reciprocating tribometer, using a steel ball on special cut steel blocks. The addition of 0.02 wt % of reduced graphene oxide led to an improvement of the tribological behavior compared to the pristine engine oil, by significantly lowering the friction coefficient by 5% in the boundary lubrication regime. Both the surfaces and the reduced graphene oxide additive were thoroughly characterized by microscopic and optical spectroscopy techniques. We also verified that a protective layer was formed between the worn surfaces, due to the presence of reduced graphene oxide. Carbon accumulation and various additive elements such as Ca, Zn, S and P were detected on the rubbing surfaces of both the ball and the block through energy-dispersive X-ray spectroscopy. Finally, it was shown that the wear scar diameter on the surface of the steel ball was lower by 3%, upon testing the engine oil sample containing reduced graphene oxide at concentration 0.02 wt %, compared to the control sample.
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This study prognoses the remaining useful life of a turbofan engine using a deep learning model, which is essential for the health management of an engine. The proposed deep learning model affords a significantly improved accuracy by organizing networks with a one-dimensional convolutional neural network, long short-term memory, and bidirectional long short-term memory. In particular, this paper investigates two practical and crucial issues in applying the deep learning model for system prognosis. The first is the requirement of numerous sensors for different components, i.e., the curse of dimensionality. Second, the deep neural network cannot identify the problematic component of the turbofan engine due to its "black box" property. This study thus employs dimensionality reduction and Shapley additive explanation (SHAP) techniques. Dimensionality reduction in the model reduces the complexity and prevents overfitting, while maintaining high accuracy. SHAP analyzes and visualizes the black box to identify the sensors. The experimental results demonstrate the high accuracy and efficiency of the proposed model with dimensionality reduction and show that SHAP enhances the explainability in a conventional deep learning model for system prognosis.
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In order to improve the biological activity of hydroxyapatite (HA), a multi-substituted HA (SHA) nanopowder with the chemical composition of Ca9.5Mg0.25Sr0.25(PO4)5.5(SiO4)0.5(OH)1.2F0.8 was synthesized using the microwave-assisted method. X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) revealed that all ions were substituted in the HA crystal lattice. The HA and SHA nanoparticles had a semi-spherical morphology with the average size of 90 and 80 nm, respectively. In-vitro bioactivity assessments showed that after the 28-day immersion of the samples in the simulated body fluid, the morphology of the precipitated apatites on the surface of the HA sample still consisted of spherical particles with a cauliflower-like structure. However, in the SHA sample, the morphology of the precipitated apatites was changed to a nanorod-like one similar to the bone-like apatite, which may be attributed the presence of Sr in the precipitated apatites. The results showed that the release of the substituted ions not only had no adverse effect on the cell viability and cell attachment, but also enhanced the alkaline phosphatase activity of MG63 osteoblast like cells in the SHA group, as compared to the HA and control groups. The results indicated that the simultaneous substitution of Si, Mg, Sr, and F in HA nanoparticles could effectively promote bioactivity, cell proliferation and differentiation. This novel HA composition could be, therefore, well used for implant coating, bone tissue engineering and other orthopedic applications.
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Durapatita , Microondas , Apatitas , Microscopía Electrónica de Rastreo , Osteoblastos , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
The development of a lightweight, low-power, user-interactive three-dimensional (3D) touchless display in which a human stimulus can be detected and simultaneously visualized in noncontact mode is of great interest. Here, we present a user-interactive 3D touchless sensing display based on multiorder reflection structural colors (SCs) of a thin, solid-state block copolymer (BCP) photonic crystal (PC). Full-visible-range SCs are developed in a BCP PC consisting of alternating lamellae, one of which contains a chemically cross-linked, interpenetrated hydrogel network. The absorption of a nonvolatile ionic liquid into the domains of the interpenetrated network allows for further manipulation of SC by using multiple-order photonic reflections, giving rise to unprecedented visible SCs arising from reflective color mixing. Furthermore, by using a hygroscopic ionic liquid ink, a printable 3D touchless interactive display is created where 3D position of a human finger is efficiently visualized in different SCs as a function of finger-to-display distance.
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It is essential for 3D-printed intra-oral appliances to be able to withstand the mechanical and microbial insult existent in the harsh environment of the oral cavity. Poly(methyl methacrylate) (PMMA)-based appliances are widely used in dentistry. Hence, the present study aimed to evaluate the role of nanodiamonds (NDs) as fillers to enhance the resistance to friction and wear. Using a solution-based mixing technique, 0.1 wt% ND was incorporated into the PMMA, and specimens were 3D-printed for tribological and bacterial analysis. The control specimens without ND fillers were tested against specimens with both amine-functionalized NDs (A-ND) and pure non-functionalized NDs (ND). The surface hardness test revealed a statistically significant increase in the Vickers micro-hardness (p < 0.001) in the nanocomposite groups. There was a significant reduction in the coefficient of friction (COF) (p < 0.01) in both the ND and A-ND nanocomposites compared to the stainless steel (SS) counter surfaces. However, for titanium (Ti)-based specimens, the COF of the control group was similar to that of A-ND but lower than that of ND. The wear resistance evaluation revealed that both the ND and A-ND groups displayed enhanced resistance to surface loss in comparison to the controls for both SS and Ti counter-surfaces (p < 0.001). Furthermore, both A-ND and ND exhibited significantly enhanced resistance to the formation of Streptococcus mutans biofilms after 48 h (p < 0.01) compared to the control group. Hence, we concluded that the addition of 0.1 wt% ND in the PMMA-based resin for 3D printing resulted in significant improvement in properties such as COF, wear resistance, and resistance to S. mutans, without any notable impact associated with the functionalization of the NDs.
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Nanodiamantes , Polimetil Metacrilato , Antibacterianos/farmacología , Ensayo de Materiales , Impresión Tridimensional , Propiedades de SuperficieRESUMEN
Physical changes in arranged silver nanowires were monitored during progressive heating inside a transmission electron microscope. Using the in-situ experimental method, overall variation of silver nanowires and movement of the silver atoms could be assessed. The physical morphology of silver nanowires was rapidly transformed above 350 °C as they fused with each other, which led to extrusion of the silver atoms. Around 550 °C, silver nanowires were almost fused into one, filling a relatively large void between silver nanowires. However, above 575 °C, the united silver nanowire was completely cut off, starting from the region that was suspected to have defects. For the first time, the fusion of arranged silver nanowires and the configurational changes of silver atoms during heating were visualized, and the migration between silver atoms and the damage mechanism of silver nanowires were assessed. Moreover, the relationship of physical morphology and electrical property of silver nanowires according to the temperature were investigated using the ex-situ experimental method. As silver nanowires started to split at 300 °C, the electrical conductivity deteriorated greatly. Beyond 350 °C, the electrical conductivity was completely lost while silver nanowires disintegrated rapidly, and silver nanowires completely disappeared at 450 °C.
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C60 fullerene has been utilized in various applications, including low friction and wear coatings, due to its unique molecular structure. In this work, molecular dynamics simulations were conducted to assess the nano-mechanical behaviour of a single C60 fullerene and its crystallized structure. A single C60 model and a model of a face-centred cubic structured C60 crystal with a one-unit-cell thickness were prepared for compression and unloading simulations based on the adaptive intermolecular reactive empirical bond-order potential for carbon. Force-displacement curves and molecule-averaged virial stresses were obtained during the simulation. The models applied during the compression and unloading processes were visualized to confirm the deformation behaviour. Both the single and crystal C60 models showed a perfectly reversible deformation before the point of force decrease that occurred during compression. In particular, the face-centred cubic structure of the crystal C60 model was severely altered during compression before the individual C60 molecules experienced permanent deformation. The maximum values of the normal virial stress in the compression direction before the permanent deformation of the molecules were almost same for both the single and crystallized models.
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This paper presents a wearable hand module which was made of five fiber Bragg grating (FBG) strain sensor and algorithms to achieve high accuracy even when worn on different hand sizes of users. For real-time calculation with high accuracy, FBG strain sensors move continuously according to the size of the hand and the bending of the joint. Representatively, four algorithms were proposed; point strain (PTS), area summation (AREA), proportional summation (PS), and PS/interference (PS/I or PS/I_α). For more accurate and efficient assessments, 3D printed hand replica with different finger sizes was adopted and quantitative evaluations were performed for index~little fingers (77 to 117 mm) and thumb (68~78 mm). For index~little fingers, the optimized algorithms were PS and PS/I_α. For thumb, the optimized algorithms were PS/I_α and AREA. The average error angle of the wearable hand module was observed to be 0.47 ± 2.51° and mean absolute error (MAE) was achieved at 1.63 ± 1.97°. These results showed that more accurate hand modules than other glove modules applied to different hand sizes can be manufactured using FBG strain sensors which move continuously and algorithms for tracking this movable FBG sensors.
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Técnicas Biosensibles , Dedos/anatomía & histología , Mano/anatomía & histología , Dispositivos Electrónicos Vestibles , Algoritmos , Humanos , Impresión TridimensionalRESUMEN
In this work, highly lubricous hyaluronic acid-silica (HA-SiO2) nanohybrid coatings were fabricated through a sequential process consisting of a sol-gel followed by electrophoretic deposition (EPD). SiO2 nanoparticles were uniformly distributed in the coating layers, and the coating thickness was identified as approximately 1-2⯵m regardless of the amount of SiO2. Incorporation of SiO2 into the HA polymer matrix enhanced the mechanical stability of the nanohybrid coatings, indicating greater interfacial bonding strength compared to HA coating layers alone. In addition, due to improved stability, the nanohybrid coatings showed excellent biolubrication properties, which were evaluated with a tribological experiment. These results indicate that the nanohybrid coatings have great potential to be used in biomedical applications that require superior biolubrication properties.
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Tecnología Biomédica , Ácido Hialurónico/química , Hidrogeles/química , Nanopartículas/química , Dióxido de Silicio/química , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Mechanically robust, biocompatible and corrosion resistant Ag doped NiTi (NiTi/Ag) coatings were formed on implant grade commercially pure titanium substrates by R.F. magnetron sputtering. Five samples with varying silver content (0, 1, 3, 7, and 10â¯at.%) were prepared by controlling the power applied to Ag and NiTi targets. The intensity of X-ray photoelectron spectra peaks corresponding to Ni2p, Ti2p, Ag3d components were found proportional to respective coating compositions. The soft Ag crystallites were decreased the roughness and crystallinity of NiTi/Ag. Among all compositions, NiTi/Ag coating with 3â¯at.% Ag exhibited lowest friction coefficient (0.1) and wear rate (0.69â¯×â¯10-07â¯mm3/Nâ¯∗â¯mm). Electrochemical corrosion measurements indicated that Ag incorporation increased the corrosion resistance of NiTi. Increase in Ag content shifted Ecorr values in the anodic direction, and reduced the current density by one-order-of-magnitude. When cultured on NiTi/Ag coating with 3â¯at.% Ag, human dermal fibroblast neonatal cells demonstrated highest cell viability. The fluorescence micrographic image of the immunostained cells showed a well grown actin filament network. Overall, NiTi/Ag coated titanium substrates were found to be a promising orthopedic implant material.
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Aleaciones/farmacología , Materiales Biocompatibles Revestidos/farmacología , Ensayo de Materiales/métodos , Ondas de Radio , Plata/farmacología , Titanio/farmacología , Corrosión , Dermis/citología , Impedancia Eléctrica , Técnicas Electroquímicas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fricción , Humanos , Microscopía de Fuerza Atómica , Espectroscopía de Fotoelectrones , Propiedades de SuperficieRESUMEN
In this study, SiN x/BN periodical nanolayered coatings (PNCs) are developed. PNCs were deposited at the room temperature on plastic and glass substrates. They demonstrate the excellent mechanical durability of inorganic materials and optical transparency and flexibility of organic ones. The 150 nm thick PNC shows optical transparency, sapphire-like hardness, high wear protection, and flexibility. Such a coating with a superior combination of optical and mechanical properties has not been reported previously.
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BACKGROUND: The risk for obesity-related diseases increases with the prevalence of obesity. In obesity, adipokines secreted from adipose tissue induce inflammation, causing adverse effects. Recently, adipokines such as apelin, visfatin, and chemerin have been studied. Long-term resistance training improves health in middle-aged women by improving metabolic risk factors, body composition, and muscle strength. However, there is still a lack of evidence on the association of apelin concentration with different exercise types in middle-aged obese women This study aimed to investigate the effects of 8 weeks of aerobic and resistance exercises on apelin-12 and apelin-36 levels and thereby verify the effects of different exercise types in obese, middle-aged women. METHODS: Participants were middle-aged women aged 50-61 years, with no experience of systematic exercise in the last 6 months, and met the WHO obesity criteria for the Asia-Pacific region of waist circumference ≥ 80 cm and body fat percentage ≥ 30%. Subjects were selected and allocated to the aerobic exercise, resistance exercise, or no exercise group by block randomization. Body weight, body fat, and body mass index were measured by bioelectrical impedance analysis. Analysis of variance, the t-test, and Tukey's post-hoc test were performed. RESULTS: A total of 24 participants were selected with eight participants in each group. Both aerobic and resistance exercises were effective in altering the physical composition, showing significant decreases in weight, waist circumference, BMI, and body fat. The aerobic and resistance exercise group showed a significant, positive change in apelin-12 levels. CONCLUSIONS: In obese individuals, aerobic and resistance exercise were effective in improving obesity and reducing blood apelin-12 concentration, which is closely correlated with indicators of metabolic syndrome. Future research should focus on comparing the response of apelin to exercise in obese subjects treated with only dietary control and the response in the obese subjects of different ages and sex. TRIAL REGISTRATION: No. 1040917-201,506-BR-153-04 , Clinical Research Information Service (CRIS), Republic of Korea (05 October 2018, retrospectively registered).
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Apelina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Obesidad/metabolismo , Obesidad/terapia , Entrenamiento de Fuerza , Composición Corporal , Índice de Masa Corporal , Peso Corporal , Ejercicio Físico/fisiología , Terapia por Ejercicio , Femenino , Humanos , Masculino , Síndrome Metabólico , Persona de Mediana Edad , República de Corea , Estudios RetrospectivosRESUMEN
Material loss and plastic deformation induced by frictional interactions at moving mechanical interfaces continue to be major issues responsible for efficiency and performance degradation of systems. Establishment of fully elastic interactions in the contact region without compromising the structural rigidity and integrity of materials represents a promising solution. In this study, we report on improving the elasticity, damping properties, ductility and wear resistance of diamond-like carbon (DLC) coatings through introducing an immobilized C60 cluster layer. The C60 clusters were immobilized using cysteamine (HS(CH2)2NH2) self-assembled monolayers (SAMs) attached to a pre-sputtered Au layer. A Ni adhesive layer was deposited onto plasma cleaned Si (100) substrates prior to Au, SAM-C60, and DLC deposition. Precise dynamic ultra nano-indentation tests indicated a drastic improvement in elasticity and damping capacity of the C60-DLC hybrid (Ni-Au-SAM/C60-DLC) multilayer coating compared to those of the C60-free (Ni-Au-DLC) multilayer. The behavior of the coatings under reciprocating contact conditions was evaluated. Quantification of the resistance of the coatings against wear and permanent deformation revealed a significant improvement in the wear rate from â¼3.38 × 10-8 to â¼5.14 × 10-10 mm3 N-1 mm-1 upon incorporation of the immobilized C60 clusters. The corresponding mechanisms were assessed through experiments and finite element (FE) simulations.
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Biophysical properties are intimately connected to metastatic functions and aggressiveness in cancers. Especially, cellular stiffness is regarded as a biomarker for the understanding of metastatic potential and drug sensitivity. Here, protease-mediated changes of cortical stiffness are identified due to the deformation of cytoskeleton alignment at a cortex. For the past few decades, membrane type 1-matrix metalloproteinase (MT1-MMP) has been well known as a kernel protease enriched in podosomes during metastasis for extracellular matrix degradation. However, the biophysical significance of MT1-MMP expressing cancer cells is still unknown. Therefore, the nanomechanics of cancer cells is analyzed by a nanoindentation using a microsphere-attached cantilever of atomic force microscopy (AFM). In conclusion, the results suggest that MT1-MMP has contributed as a key regulator in cytoskeletal deformation related with cancer metastasis. Particularly, the AFM-based nanoindentation system for the monitoring of cortical nanomechanics will be crucial to understand molecular networks in cancers.