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A human can intuitively perceive and comprehend complicated tactile information because the cutaneous receptors distributed in the fingertip skin receive different tactile stimuli simultaneously and the tactile signals are immediately transmitted to the brain. Although many research groups have attempted to mimic the structure and function of human skin, it remains a challenge to implement human-like tactile perception process inside one system. In this study, we developed a real-time and multimodal tactile system that mimics the function of cutaneous receptors and the transduction of tactile stimuli from receptors to the brain, by using multiple sensors, a signal processing and transmission circuit module, and a signal analysis module. The proposed system is capable of simultaneously acquiring four types of decoupled tactile information with a compact system, thereby enabling differentiation between various tactile stimuli, texture characteristics, and consecutive complex motions. This skin-like three-dimensional integrated design provides further opportunities in multimodal tactile sensing systems.

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Sulforaphane (SFN) is a naturally occurring isothiocyanate that is abundant in many cruciferous vegetables, such as broccoli and cauliflower, and it has been observed to exert numerous biological activities. In the present study, we investigate the effect of SFN on eNOS, a key regulatory enzyme of vascular homeostasis and underlying intracellular pathways, in human endothelial EA.hy926 cells. The results indicate that SFN treatment significantly increases NO production and eNOS phosphorylation in a time- and dose-dependent fashion and also augments Akt phosphorylation in a time- and dose-dependent manner. Meanwhile, pretreatment with LY294002 (a specific PI3K inhibitor) suppresses the phosphorylation of eNOS and NO production. Furthermore, SFN time- and dose-dependently induces the phosphorylation of Src kinase, a further upstream regulator of PI3K, while PP2 pretreatment (a specific Src inhibitor) eliminates the increase in phosphorylated Akt, eNOS and the production of NO derived from eNOS. Overall, the present study uncovers a novel effect of SFN to stimulate eNOS activity in EA.hy926 cells by regulating NO bioavailability. These findings provide clear evidence that SFN regulates eNOS activity and NO bioavailability, suggesting a promising therapeutic candidate to prevent endothelial dysfunction, atherosclerosis and other cardiovascular diseases.

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Hierarchical structures in nature provide unique functions for living organisms that can inspire technology. Nanoscale hierarchical structured surfaces are essential to realize the dual functions of non-wetting and transparency for applications such as cover glasses and windows; however, these structures are challenging to fabricate. In this study, nano-hierarchical structured glass surfaces were fabricated using multi-step colloidal lithography and etching to obtain tunable morphology. Nanostructured surfaces of mono-pillar structures of diameter 120 and 350 nm and hierarchical-pillar structures of their combinations exhibited superhydrophobicity after perfluoropolyether coating. In particular, the hierarchical nanosurfaces showed excellent non-wetting properties with the apparent, advancing, and receding water contact angles exceeding 177° and contact angle hysteresis below 1°. Water bouncing behaviors - contact time, spreading diameter, and shape of the bouncing motion were also evaluated according to the Weber number to examine the robustness of superhydrophobicity. Hierarchical nanosurfaces showed larger spreading diameters than mono-nanosurfaces with 14 bounces, indicating minimal energy loss from friction, as can be explained by the effective slip length. Furthermore, the nano-hierarchical structures exhibited better transmittance for wide angles of incidence up to 70° than mono-nanostructures owing to their reduced scattering area and multi-periodicity.

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Sulforaphane, a natural phytochemical compound found in various cruciferous vegetables, has been discovered to present anti-cancer properties. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in gastric cancer metastasis. However, the role of sulforaphane in MMP-9 expression in gastric cancer is not yet defined. Nicotine, a psychoactive alkaloid found in tobacco, is associated with the development of gastric cancer. Here, we found that sulforaphane suppresses the nicotine-mediated induction of MMP-9 in human gastric cancer cells. We discovered that reactive oxygen species (ROS) and MAPKs (p38 MAPK, Erk1/2) are involved in nicotine-induced MMP-9 expression. AP-1 and NF-κB are the critical transcription factors in MMP-9 expression. ROS/MAPK (p38 MAPK, Erk1/2) and ROS functioned as upstream signaling of AP-1 and NF-κB, respectively. Sulforaphane suppresses the nicotine-induced MMP-9 by inhibiting ROS-mediated MAPK (p38 MAPK, Erk1/2)/AP-1 and ROS-mediated NF-κB signaling axes, which in turn inhibit cell invasion in human gastric cancer AGS cells. Therefore, the current study provides valuable evidence for developing sulforaphane as a new anti-invasion strategy for human gastric cancer therapy.

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In this study, a parasitic capacitance-free tactile sensor with a floating electrode that is capable of identifying actual physical contact pressure by distinguishing from parasitic effects and applicable to sensor arrays is presented. Although capacitive pressure sensors are known for their excellent pressure sensing capabilities in wide range with high sensitivity, they tend to suffer from a parasitic capacitance noise and unwanted proximity effects. Electromagnetic interference shielding was conventionally used to prevent this noise; however, it was not entirely successful in multicell array sensors. Parasitic capacitance-free method involves the use of a floating electrode, which functions as a contact trigger by causing sudden changes in capacitance only when the actual physical contact pressure has been applied or removed. The proposed method is robust, consistent, and precise. Experimental results show a wide range of pressure response up to 2.4 MPa with a sensitivity of 0.179 MPa-1 (up to 0.74 MPa) and negligible hysteresis.

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In order to realize a transition from conventional to stretchable electronics, it is necessary to make a universal stretchable circuit board in which passive/active components can be robustly integrated. We developed a stretchable printed circuit board (s-PCB) platform that enables easy and reliable integration of various electronic components by utilizing a modulus-gradient polymeric substrate, liquid metal amalgam (LMA) circuit traces, and Ag nanowire (AgNW) contact pads. Due to the LMA-AgNW biphasic structure of interconnection, the LMA is hermetically sealed by a homogeneous interface, realizing complete leak-free characteristics. Furthermore, integration reliability is successfully achieved by local strain control of the stretchable substrate with a selective glass fiber reinforcement (GFR). A strain localization derived by GFR makes almost 50,000% of strain difference within the board, and the amount of deformation applied to the constituent elements can be engineered. We finally demonstrated that the proposed integrated platform can be utilized as a universal s-PCB capable of integrating rigid/conventional electronic components and soft material-based functional elements with negligible signal distortion under various mechanical deformations.

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Micro-RNA-21 (miR-21) is a vital regulator of colorectal cancer (CRC) progression and has emerged as a potential therapeutic target in CRC treatment. Our study using real-time PCR assay found that a secondary bile acid, lithocholic acid (LCA), stimulated the expression of miR21 in the CRC cell lines. Promoter activity assay showed that LCA strongly stimulated miR21 promoter activity in HCT116 cells in a time- and dose-dependent manner. Studies of chemical inhibitors and miR21 promoter mutants indicated that Erk1/2 signaling, AP-1 transcription factor, and STAT3 are major signals involved in the mechanism of LCA-induced miR21 in HCT116 cells. The elevation of miR21 expression was upstream of the phosphatase and tensin homolog (PTEN) inhibition, and CRC cell proliferation enhancement that was shown to be possibly mediated by PI3K/AKT signaling activation. This study is the first to report that LCA affects miR21 expression in CRC cells, providing us with a better understanding of the cancer-promoting mechanism of bile acids that have been described as the very first promoters of CRC progression.

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Cochlear implants (CIs) have become the standard treatment for severe-to-profound sensorineural hearing loss. Conventional CIs have some challenges, such as the use of extracorporeal devices, and high power consumption for frequency analysis. To overcome these, artificial basilar membranes (ABMs) made of piezoelectric materials have been studied. This study aimed to verify the conceptual idea of a totally implantable ABM system. A prototype of the totally implantable system composed of the ABM developed in previous research, an electronic module (EM) for the amplification of electrical output from the ABM, and electrode was developed. We investigated the feasibility of the ABM system and obtained meaningful auditory brainstem responses of deafened guinea pigs by implanting the electrode of the ABM system. Also, an optimal method of coupling the ABM system to the human ossicle for transducing sound waves into electrical signals using the middle ear vibration was studied and the electrical signal output according to the sound stimuli was measured successfully. Although the overall power output from the ABM system is still less than the conventional CIs and further improvements to the ABM system are needed, we found a possibility of the developed ABM system as a totally implantable CIs in the future.

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Slippery liquid-infused porous surfaces (SLIPSs) have been actively studied to improve the limitations of superhydrophobic (SHP) surfaces, especially the defects of the nonwetting chemical coating layer and the weak mechanical robustness of surface micro/nanostructures. However, the SLIPSs also have several drawbacks including volatilization and leakage of lubricant caused by long-term usage. In this study, we suggest the use of icephobic, highly transparent, and self-healing solid slippery surface to overcome the limitations of both surfaces (SLIPS and SHP) by combining specific biomimetic morphology and intrinsic properties of paraffin wax. A moth-eye mimicking nanopillar structure was prepared instead of a porous structure and was coated with solid paraffin wax for water repellence. Moth-eye structures enable high surface transparency based on antireflective effect, and the paraffin layer can recover from damage due to sunlight exposure. Furthermore, the paraffin coating on the nanopillars provides an air trap, resulting in a low heat transfer rate, increasing freezing time and reducing adhesion strength between the ice droplet and the surface. The heat transfer model was also calculated to elucidate the effects of the nanopillar height and paraffin layer thickness. The antireflection and freezing time of the surfaces are enhanced with increase in nanopillar height. The paraffin layer slightly deteriorates the transmittance but enhances the icephobicity. The solar cell efficiency using a biomimetic solid slippery surface is higher than that of bare glass due to the antireflective effect. This integrated biomimetic solid slippery surface is multifunctional due to its self-cleaning, anti-icing, antireflection, and self-healing properties and may replace SLIPS and SHP surfaces.

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Durability and multifunctionality are very important factors for human skinlike tactile sensors for measuring physical stimuli if they provide reasonable pressure measurement range and sensitivity. Here, we propose a step tactile sensor with a simple processing unit, showing high repeatability and mechanical stability without drifting caused by thermal and geometrical noise. The proposed sensor, similar to a switch mechanism, detects the applied pressure discretely and has a wide pressure range of 2 kPa to 1.2 MPa according to its geometry. The developed tactile sensor can be designed and fabricated in various morphologies to detect a wide range of tactile stimuli, which help in customizing the sensor as per user demand for practical applications such as a prosthesis arm or hand. It is also easy to extend the sensor size to cover a large area owing to the simple fabrication process by using a 3D printer. Furthermore, with the addition of a flexible exterior layer of leuco dyes and the polydimethylsiloxane mixture, the color of a step tactile sensor not only resembles that of human skin color but also changes its color depending on the temperature changes as human skin does. Thus, the function of a pressure and temperature indicator in a flexible step sensor finds practical applications in various fields, including but not limited to prosthetic applications for the customized and comfortable usage.

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Mechanoreceptors in a fingertip convert external tactile stimulations into electrical signals, which are transmitted by the nervous system through synaptic transmitters and then perceived by the brain with high accuracy and reliability. Inspired by the human synapse system, this paper reports a robust tactile sensing system consisting of a remote touch tip and a magnetic synapse. External pressure on the remote touch tip is transferred in the form of air pressure to the magnetic synapse, where its variation is converted into electrical signals. The developed system has high sensitivity and a wide dynamic range. The remote sensing system demonstrated tactile capabilities over wide pressure range with a minimum detectable pressure of 6 Pa. In addition, it could measure tactile stimulation up to 1,000 Hz without distortion and hysteresis, owing to the separation of the touching and sensing parts. The excellent performance of the system in terms of surface texture discrimination, heartbeat measurement from the human wrist, and satisfactory detection quality in water indicates that it has considerable potential for various mechanosensory applications in different environments.

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Several studies have demonstrated a correlation between the expression of early growth response gene-1 (EGR-1) and the progression of gastric cancers at advanced stages. However, the effects of EGR-1 expression on human gastric cancer progression, particularly on precancerous lesions, have not been investigated. In this study, we evaluate EGR-1 expression levels in target mucosa from patients with early gastric cancer and precancerous lesions, and assess whether EGR-1 expression affects the oncogenic phenotypes of human gastric cancer cells. EGR-1 protein levels were measured in tissues from subjects with normal mucosa (n=6), low-grade dysplasia (n=6), high-grade dysplasia (n=4) and adenocarcinoma (n=3) using enzyme-linked immunosorbent assay and immunohistochemistry analyses. We also investigated the role of EGR-1 in tumor cell behavior by transiently expressing a dominant active EGR-1 variant in cultured cells. A positive correlation was observed between EGR-1 expression and gastric carcinogenesis (P=0.016). Furthermore, there was an increase in nuclear and cytoplasmic expression of EGR-1 in accordance with the histological grade (P for trends=0.003 and 0.003, respectively), and a positive association between the sum of the nuclear and cytoplasmic EGR-1 expression values and the histological grade (P=0.003). In addition, transient overexpression of EGR-1 enhanced cell proliferation, stimulated cell migration, and promoted the phosphorylation of p38 MAPK and AKT in gastric cancer cells in vitro. Our findings demonstrate that EGR-1 may contribute to the early stages of gastric carcinogenesis via the alteration of tumor cell behaviors.

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High sensitive flexible and wearable devices which can detect delicate touches have attracted considerable attentions from researchers for various promising applications. This research was aimed at enhancing the sensitivity of a MWCNT/PDMS piezoresistive tactile sensor through modification of its surface texture in the form of micropillars on MWCNT/PDMS film and subsequent low energy Ar⁺ ion beam treatment of the micropillars. The introduction of straight micropillars on the MWCNT/PDMS surface increased the sensitivity under gentle touch. Low energy ion beam treatment was performed to induce a stiff layer on the exposed surface of the micropillar structured MWCNT/PDMS film. The low energy ion bombardment stabilized the electrical properties of the MWCNT/PDMS surface and tuned the curvature of micropillars according to the treatment conditions. The straight micropillars which were treated by Ar⁺ ion with an incident angle of 0° demonstrated the enhanced sensitivity under normal pressure and the curved micropillars which were treated with Ar⁺ ion with an incident angle of 60° differentiated the direction of an applied shear pressure. The ion beam treatment on micropillar structured MWCNT/PDMS tactile sensors can thus be applied to reliable sensing under gentle touch with directional discrimination.

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Flexible tactile sensors capable of detecting the magnitude and direction of the applied force together are of great interest for application in human-interactive robots, prosthetics, and bionic arms/feet. Human skin contains excellent tactile sensing elements, mechanoreceptors, which detect their assigned tactile stimuli and transduce them into electrical signals. The transduced signals are transmitted through separated nerve fibers to the central nerve system without complicated signal processing. Inspired by the function and organization of human skin, we present a piezoresistive type tactile sensor capable of discriminating the direction and magnitude of stimulations without further signal processing. Our tactile sensor is based on a flexible core and four sidewall structures of elastomer, where highly sensitive interlocking piezoresistive type sensing elements are embedded. We demonstrate the discriminating normal pressure and shear force simultaneously without interference between the applied forces. The developed sensor can detect down to 128 Pa in normal pressure and 0.08 N in shear force, respectively. The developed sensor can be applied in the prosthetic arms requiring the restoration of tactile sensation to discriminate the feeling of normal and shear force like human skin.

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This paper presents the development of a piezoelectric artificial cochlea (PAC) device capable of analyzing vibratory signal inputs and converting them into electrical signal outputs without an external power source by mimicking the function of human cochlea within an audible frequency range. The PAC consists of an artificial basilar membrane (ABM) part and an implantable packaged part. The packaged part provides a liquid environment through which incoming vibrations are transmitted to the membrane part. The membrane part responds to the transmitted signal, and the local area of the ABM part vibrates differently depending on its local resonant frequency. The membrane was designed to have a logarithmically varying width from 0.97 mm to 8.0 mm along the 28 mm length. By incorporating a micro-actuator in an experimental platform for the package part that mimics the function of a stapes bone in the middle ear, we created a similar experimental environment to cochlea where the human basilar membrane vibrates. The mechanical and electrical responses of fabricated PAC were measured with a laser Doppler vibrometer and a data acquisition system, and were compared with simulation results. Finally, the fabricated PAC in a biocompatible package was developed and its mechanical and electrical characteristics were measured. The experimental results shows successful frequency separation of incoming mechanical signal from micro-actuator into frequency bandwidth within the 0.4 kHz-5 kHz range.

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Stretchable electronic skins with multidirectional force-sensing capabilities are of great importance in robotics, prosthetics, and rehabilitation devices. Inspired by the interlocked microstructures found in epidermal-dermal ridges in human skin, piezoresistive interlocked microdome arrays are employed for stress-direction-sensitive, stretchable electronic skins. Here we show that these arrays possess highly sensitive detection capability of various mechanical stimuli including normal, shear, stretching, bending, and twisting forces. Furthermore, the unique geometry of interlocked microdome arrays enables the differentiation of various mechanical stimuli because the arrays exhibit different levels of deformation depending on the direction of applied forces, thus providing different sensory output patterns. In addition, we show that the electronic skins attached on human skin in the arm and wrist areas are able to distinguish various mechanical stimuli applied in different directions and can selectively monitor different intensities and directions of air flows and vibrations.

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The development of flexible electronic skins with high sensitivities and multimodal sensing capabilities is of great interest for applications ranging from human healthcare monitoring to robotic skins to prosthetic limbs. Although piezoresistive composite elastomers have shown great promise in this area of research, typically poor sensitivities and low response times, as well as signal drifts with temperature, have prevented further development of these materials in electronic skin applications. Here, we introduce and demonstrate a design of flexible electronic skins based on composite elastomer films that contain interlocked microdome arrays and display giant tunneling piezoresistance. Our design substantially increases the change in contact area upon loading and enables an extreme resistance-switching behavior (ROFF/RON of ∼10(5)). This translates into high sensitivity to pressure (-15.1 kPa(-1), ∼0.2 Pa minimum detection) and rapid response/relaxation times (∼0.04 s), with a minimal dependence on temperature variation. We show that our sensors can sensitively monitor human breathing flows and voice vibrations, highlighting their potential use in wearable human-health monitoring systems.

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In this research, we have developed a multi-channel piezoelectric acoustic sensor (McPAS) that mimics the function of the natural basilar membrane capable of separating incoming acoustic signals mechanically by their frequency and generating corresponding electrical signals. The McPAS operates without an external energy source and signal processing unit with a vibrating piezoelectric thin film membrane. The shape of the vibrating membrane was chosen to be trapezoidal such that different locations of membrane have different local resonance frequencies. The length of the membrane is 28 mm and the width of the membrane varies from 1 mm to 8 mm. Multiphysics finite element analysis (FEA) was carried out to predict and design the mechanical behaviors and piezoelectric response of the McPAS model. The designed McPAS was fabricated with a MEMS fabrication process based on the simulated results. The fabricated device was tested with a mouth simulator to measure its mechanical and piezoelectrical frequency response with a laser Doppler vibrometer and acoustic signal analyzer. The experimental results show that the as fabricated McPAS can successfully separate incoming acoustic signals within the 2.5 kHz-13.5 kHz range and the maximum electrical signal output upon acoustic signal input of 94 dBSPL was 6.33 mVpp. The performance of the fabricated McPAS coincided well with the designed parameters.

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AIMS AND BACKGROUND: The aims of the current study were to evaluate whether recepteur d'origine nantais (RON) affects tumor cell behavior and oncogenic signaling pathways in colorectal cancer, and to examine the relationship of its expression with various clinicopathological parameters and patient survival. METHODS: Immunohistochemistry, Western blot and RT-PCR were used to detect the expression of the RON gene in human colorectal cancer tissue. To study the biological role of RON in tumor cell behavior and cellular signaling pathways, we used small interfering RNA (siRNA) to knock down RON gene expression in human colorectal cancer cell lines. RESULTS: Knockdown of RON inhibited the induction of the invasive growth phenotype and the activation of oncogenic signaling pathways including Akt, MAPK and ß-catenin. RON overexpression was associated with tumor size, lymphovascular invasion, depth of invasion, lymph node metastasis, distant metastasis, tumor stage and poor survival. CONCLUSIONS: These results suggest that RON overexpression may help in predicting poor clinical outcomes in colorectal cancer.

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