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Neural electrodes have been widely used to monitor neurological disorders and have a major impact on neuroscience, whereas traditional electrodes are limited to their inherent high impedance, which makes them insensitive to weak signals during recording neural signals. Herein, we developed a neural electrode based on the graphene/Ag van der Waals heterostructure for improving the detection sensitivity and signal-to-noise ratio (SNR). The impedance of the graphene/Ag electrode is reduced to 161.4 ± 13.4 MΩ μm

Background Although the aberrant activation of NOTCH1 pathway causes a malignant progression of renal cell carcinoma (RCC), the precise molecular mechanisms behind the potential action of pro-oncogenic NOTCH1/HES1 axis remain elusive. Here, we examined the role of tumor suppressive miR-138–2 in the regulation of NOTCH1-HES1-mediated promotion of RCC. Methods This study employed bioinformatics, xenotransplant mouse models, ChIP assay, luciferase reporter assay, functional experiments, real-time PCR and Western blot analysis to explore the mechanisms of miR-138–2 in the regulation of NOTCH1-HES1-mediated promotion of RCC, and further explored miR-138–2-containing combination treatment strategies. Results There existed a positive correlation between down-regulation of miR-138 and the aberrant augmentation of NOTCH1/HES1 regulatory axis. Mechanistically, HES1 directly bound to miR-138–2 promoter region and thereby attenuated the transcription of miR-138-5p as well as miR-138–2-3p. Further analysis revealed that miR-138-5p as well as miR-138–2-3p synergistically impairs pro-oncogenic NOTCH1 pathway through the direct targeting of APH1A, MAML1 and NOTCH1. Conclusions Collectively, our current study strongly suggests that miR-138–2 acts as a novel epigenetic regulator of pro-oncogenic NOTCH1 pathway, and that the potential feedback regulatory loop composed of HES1, miR-138–2 and NOTCH1 contributes to the malignant development of RCC. From the clinical point of view, this feedback regulatory loop might be a promising therapeutic target to treat the patients with RCC.

Background The RNA-binding protein (RBP) played an important role in tumors. FSCN1 functioned as an oncogene in bladder carcinoma (BLCA). FSCN1 has not been reported as an RBP in BLCA. The mechanism by which FSCN1 promoted BLCA invasion and metastasis has remained unclear. Methods The FSCN1-bound RNAs in BLCA cell lines were identified using RIP-sequencing. The regulatory relationship between FSCN1 and METTL3 or TLN1 was verified by RNA immunoprecipitation (RIP), RNA pulldown assay, co-immunoprecipitation (Co-IP), western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence. The metastatic abilities of the BCLA cells were evaluated by in vitro wound healing and transwell assays, as well as in vivo models. Results TLN1 protein levels were higher in BLCA tissues compared to the paired para-tumor tissues, whereas its mRNA expression was lower in the tumors. Mechanistically, FSCN1 bound to and upregulated METTL3, which in turn repressed TLN1 mRNA expression through the latter’s 3'UTR. In addition, FSCN1 bound to the CDS region of TLN1 mRNA and promoted its translation. Knocking down FSCN1, METTL3 and TLN1 individually had an inhibitory effect on the proliferation, invasion, migration and metastasis of BLCA cells. Conclusions FSCN1 functions as an RBP to promote proliferation, invasion and migration of BLCA cells. The FSCN1/METTL3/TLN1 axis is a potential therapeutic target for BLCA.

Background Protein arginine methyltransferases (PRMTs) regulate protein biological activity by modulating arginine methylation in cancer and are increasingly recognized as potential drug targets. Inhibitors targeting PRMTs are currently in the early phases of clinical trials and more candidate drugs are needed. Flavokawain A (FKA), extracted from kava plant, has been recognized as a potential chemotherapy drug in bladder cancer (BC), but its action mechanism remains unclear. Methods We first determined the role of a type II PRMT, PRMT5, in BC tissue samples and performed cytological experiments. We then utilized bioinformatics tools, including computational simulation, virtual screening, molecular docking, and energy analysis, to identify the potential use of PRMT5 inhibitors for BC treatment. In vitro and in vivo co-IP and mutation assays were performed to elucidate the molecular mechanism of PRMT5 inhibitor. Pharmacology experiments like bio-layer interferometry, CETSA, and pull-down assays were further used to provide direct evidence of the complex binding process. Results Among PRMTs, PRMT5 was identified as a therapeutic target for BC. PRMT5 expression in BC was correlated with poor prognosis and manipulating its expression could affect cancer cell growth. Through screening and extensive experimental validation, we recognized that a natural product, FKA, was a small new inhibitor molecule for PRMT5. We noticed that the product could inhibit the action of BC, in vitro and in vivo, by inhibiting PRMT5. We further demonstrated that FKA blocks the symmetric arginine dimethylation of histone H2A and H4 by binding to Y304 and F580 of PRMT5. Conclusions In summary, our research strongly suggests that PRMT5 is a potential epigenetic therapeutic target in bladder cancer, and that FKA can be used as a targeted inhibitor of PRMT5 for the treatment of bladder cancer.

In this paper, a 3D printing system for a thermal battery electrode ink film is set up and investigated based on the on-demand microdroplet ejection technology. The optimal structural dimensions of the spray chamber and metal membrane of the micronozzle are determined via simulation analysis. The workflow and functional requirements of the printing system are set up. The printing system includes a pretreatment system, piezoelectric micronozzle, motion control system, piezoelectric drive system, sealing system, and liquid conveying system. Different printing parameters are compared to obtain optimized printing parameters, which can be attributed to the optimal pattern of the film. The feasibility and controllability of 3D printing methods are verified by printing tests. The size and output speed of the droplets can be controlled by adjusting the amplitude and frequency of the driving waveform acting on the piezoelectric actuator. So, the required shape and thickness of the film can be achieved. An ink film in terms of nozzle diameter = 0.6 mm, printing height = 8 mm, wiring width = 1 mm, input voltage = 3 V and square wave signal frequency = 35 Hz can be achieved. The electrochemical performance of thin-film electrodes is crucial in thermal batteries. The voltage of the thermal battery reaches its peak and tends to flatten out at around 100 s when using this printed film. The electrical performance of the thermal batteries using the printed thin films is found to be stable. This stabilized voltage makes it applicable to thermal batteries.

Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag-S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 μM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.

Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo. The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO2 (Cr/CeO2) nanozyme increases the reduced Ce3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO2. Furthermore, Cr/CeO2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.

Finding cancer-driver genes – the genes whose mutations may transform normal cells into cancerous ones – remains a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth which we namedcancer-keeping genes(CKGs). Intervention in CKGs may rectify aberrant cell growth so that they can be adopted as therapeutic targets for cancer treatment. We developed a novel approach to identifying CKGs by extending the well-established theory of network structural controllability, which aims at finding a control scheme (i.e., a minimal set of non-overlapping control paths covering all nodes) and control nodes (driver genes) that can steer the cell from any state to the designated state. Going beyond driver genes defined by one control scheme, we introducedcontrol-hubgenes located in the middle of a control path ofeverycontrol scheme. Control hubs are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA) as a case study. All the genes on the cell cycle and p53 pathways in BLCA were identified as CKGs, showing the importance of these genes in cancer and demonstrating the power of our new method. Furthermore, sensitive CKGs that could be easily changed by structural perturbation were better suited as therapeutic targets. Six sensitive CKGs (RPS6KA3, FGFR3, N-cadherin (CDH2), EP300, caspase-1, and FN1) were subjected to small-interferencing-RNA knockdown in two BLCA cell lines to validate their cancer-suppressing effects. Knocking down RPS6KA3 in a mouse model of BLCA significantly inhibited the growth of tumor xenografts in mice. Combined, our results demonstrated the value of CKGs as therapeutic targets for cancer therapy.Key pointsFocus on genes that maintain aberrant cell growth, namedcancer-keeping genes(CKGs).Develop a novel approach for finding CKGs by extending the well-estabilished theory of network structural controllability to total network controllability.Apply the new method to bladder cancer and experimentally validated the cancer-suppressing function of six CKGs in two bladder cancer cell lines and that of one CKG in bladder cancer mice.

Neuron interface devices can be used to explore the relationships between neuron firing and synaptic transmission, as well as to diagnose and treat neurological disorders, such as epilepsy and Alzheimer’s disease. It is crucial to exploit neuron devices with high sensitivity, high biocompatibility, multifunctional integration and high-speed data processing. During the past decades, researchers have made significant progress in neural electrodes, artificial sensory neuron devices, and neuromorphic optic neuron devices. The main part of the review is divided into two sections, providing an overview of recently developed neuron interface devices for recording electrophysiological signals, as well as applications in neuromodulation, simulating the human sensory system, and achieving memory and recognition. We mainly discussed the development, characteristics, functional mechanisms, and applications of neuron devices and elucidated several key points for clinical translation. The present review highlights the advances in neuron devices on brain-computer interfaces and neuroscience research.

Atomically precise Au25(SG)18 clusters have shown great promise in near-infrared II cerebrovascular imaging, X-ray imaging, and cancer radiotherapy due to their high atomic number, unique molecular-like electronic structure, and renal clearable properties. Therefore, it is important to study the in vivo toxicity of Au25 clusters. Unfortunately, previous toxicological investigations focused on low injected doses (

Near-infrared-II (NIR-II, 1000-1700 nm) fluorescence imaging is widely used for in vivo biological imaging. With the unique electronic structures and capability of band-gap engineering, two-dimensional (2D) materials can be potential candidates for NIR-II imaging. Herein, a theoretical investigation of the electronic structure and optical properties of iodine (I)-doped monolayer MoTe

Bladder cancer is a common tumor with a high recurrence rate and high fatality rate, and its mechanism of occurrence and development remains unclear. Many proteins and metabolites reprogram at different stages of tumor development to support tumor cell growth. The moonlighting effect happens when a protein performs multiple functions simultaneously in a cell. In this study, we identified a metabolic protein, MTHFD2, which participates in the cell cycle by binding to CDK2 in bladder cancer. MTHFD2 has been shown to affect bladder cancer cell growth, which is independent of its metabolic function. We found that MTHFD2 was involved in cell cycle regulation and could encourage cell cycle progression by activating CDK2 and sequentially affecting E2F1 activation. In addition, moonlighting MTHFD2 might be regulated by the dynamics of the mitochondria. In conclusion, MTHFD2 localizes in the nucleus to perform a distinct function of catalyzing metabolic reactions. Moreover, the nuclear MTHFD2 activates CDK2 and promotes bladder cancer cell growth by modulating the cell cycle., This study showed that MTHFD2's expression is correlated with poor prognosis in bladder cancer. Moreover, it could precipitate with CDK2 in a metabolic manner and activate E2F1 through CDK2 to induce rapid cell growth. Furthermore, MTHFD2 could be transcriptionally regulated by the CDK2‐E2F1 axis and translocated into the nucleus at the G1‐S phase associated with mitochondrial fusion. These results suggest that MTHFD2 participates in the cell cycle using a non‐metabolic function, which should be considered in the development of related therapeutics.

This paper analyzed the effects of setback micro-springs on a MEMS safety and arming (S&A) device. To make up for defects related to current methods of obtaining the elastic coefficients of micro-springs, a computational formula for the elastic coefficients of S-shaped micro-springs was developed in accordance with Castigliano’s second theorem and Hooke’s law and verified for three types of setback micro-springs with different structures through finite element simulations and a self-designed testing system for the elastic coefficients of micro-springs. The testing values and the simulation values were in good agreement with the theoretical values. The results indicate that the precise measurement and calculation of the elastic coefficients of micro-springs in the transverse, longitudinal and vertical directions can be realized with the method presented in this paper. For the S-shaped setback micro-spring, the elastic coefficient in the transverse direction is the smallest and the most prone to fracture and plastic deformation. In the design of MEMS S&A devices, priority should be given to applying the deformation of the micro-spring in the longitudinal and vertical directions.

Conducting polymer actuators have shown wide application prospects in the field of biomedical sensors and micro-/nanorobotics. In order to explore more applications in biomedical sensing and robotics, it is essential to understand the actuator static behavior from an engineering perspective, before incorporating them into a design. In this article, we have established the mathematical model of a trilayer polypyrrole (PPy) cantilever actuator and validated it experimentally. The model helps in enhancing the efficiency and in improving the performance, predictability, and control of the actuator. The thermal expansion analogy, which is similar to volume change of the multilayer PPy actuator due to ion migration, has been considered to develop a mathematical model in COMSOL Multiphysics. To further validate the actuator deformation predicted by the mathematical modeling, a multilayer PPy actuator was fabricated by electrochemical synthesis and the experimentally determined deflection of the actuator was compared to simulation data. Both the theoretical and experimental results depict that the model is effective for predicting the bending behavior of multilayer PPy actuators at different input voltages.

To make up for the deficiencies in the present method of measuring microdetonator output energy, this paper uses PVDF (Polyvinylidene Fluoride) piezoelectric films as sensors and designs a system to test the output pressure of microdetonators with a 2.5 mm diameter. The average measured output pressure was 9.87GPa. In addition, detonation tests were carried out which showed that a microdetonator with a 10 mg charge could reliably detonate a JO-9C(III model) lead explosive with an 8 mg charge in a 0.7 mm air-gap. The detonation simulations for lead explosives using LS-DYNA software were consistent with the detonation test results. There was less than 5% error between the output pressure values and the test values of microdetonators. The results showed that PVDF piezoelectric films have rapid response times, high precision and low production cost in output pressure tests. The simulation model has practical significance for the quantitative evaluation of microdetonator output energy.

The manufacturing process of planar microsprings by the UV-LIGA process was introduced; the mechanism of fabrication error was analyzed from three process stages of exposure, SU-8 swelling, and corrosion; and the corresponding improvement measures were proposed. The line width of two groups of microsprings after the exposure, SU-8 swelling, and debonding was measured, and the elastic coefficients in three coordinate directions were accurately measured. The results show that the factors that affect the line width error are stable. The effects of the exposure diffraction, swelling of SU-8 glue, and debonding corrosion process on the line width size follow the order: corrosion error > swelling error > exposure error. When the line width is small, the aspect ratio of the microspring is large, and the direction of machining error is generally negative. The relative error of the elastic coefficient of microsprings in three coordinate directions is larger. The influence rule of the line width error on the elastic coefficient follows the order: kerrory > kerrorx > kerrorz.

As the transmembrane receptor of Netrin-1, the tumor suppressor gene Unc-5 Netrin Receptor C (UNC5C) can trigger apoptosis. Although its tumor suppressor effects have been demonstrated in solid tumors such as colon cancer, there is still a lack of systematic research on its expression regulation mechanism. To address this need, we analyzed datasets from The Cancer Genome Atlas (TCGA) database, including multi-omics data for 32 types of cancers and 10,967 cases. Analysis of these data revealed a trend of significantly decreased UNC5C expression in 16 types of solid tumors. Additionally, low UNC5C expression is related to poor prognosis of five types of tumors and restoring the expression of UNC5C can effectively inhibit the proliferation potential of renal cancer cells. Promoter DNA methylation, chromatin remodeling-mediated epigenetic regulation, transcriptional inhibition, RNA-binding protein and miRNA-mediated post-transcriptional inhibition, genetic changes caused by deep deletion and truncated mutations, and ubiquitinating enzyme-mediated protein degradation can synergistically cause the down-regulation of UNC5C expression in solid tumors. This study is the first to analyze the comprehensive molecular mechanism of down-regulation of the tumor suppressor gene UNC5C from multiple dimensions using pan-cancer data. Our results suggest that analyses of gene expression regulation relying on computational biological methods may help guide the targeted therapy of tumor suppressor gene reactivation.

Mechanical equipment fault detection is critical in industrial applications. Based on vibration signal processing and analysis, the traditional fault diagnosis method relies on rich professional knowledge and artificial experience. Achieving accurate feature extraction and fault diagnosis is difficult using such an approach. To learn the characteristics of features from data automatically, a deep learning method is used. A qualitative and quantitative method for rolling bearing faults diagnosis based on an improved convolutional deep belief network (CDBN) is proposed in this study. First, the original vibration signal is converted to the frequency signal with the fast Fourier transform to improve shallow inputs. Second, the Adam optimizer is introduced to accelerate model training and convergence speed. Finally, the model structure is optimized. A multi-layer feature fusion learning structure is put forward wherein the characterization capabilities of each layer can be fully used to improve the generalization ability of the model. In the experimental verification, a laboratory self-made bearing vibration signal dataset was used. The dataset included healthy bearings, nine single faults of different types and sizes, and three different types of composite fault signals. The results of load 0 kN and 1 kN both indicate that the proposed model has better diagnostic accuracy, with an average of 98.15% and 96.15%, compared with the traditional stacked autoencoder, artificial neural network, deep belief network, and standard CDBN. With improved diagnostic accuracy, the proposed model realizes reliable and effective qualitative and quantitative diagnosis of bearing faults.

Due to the complexity of industrial intelligent diagnosis, transfer learning-based fault diagnosis has become an evolving focus of the research field. Transfer learning uses knowledge of the source domain to identify faults in the target domain, which is a powerful tool to solve the problem of fault signal domain shift. However, existing methods have a limitation on multiple target domains. In other words, for different domains, respective transfer tasks are necessary. To seek a breakthrough, a adversarial multi-domain adaptation (AMDA) fault diagnosis method is proposed, realizing the fault diagnosis of multiple target domains by using the knowledge of a single source domain. AMDA is divided into three parts, namely, feature extractor, fault classifier and domain classifier. Through multi-domain adversarial learning, feature extractor and domain classifier mine the knowledge shared by multiple domains, and fault classifier can identify fault features distributed in different domains. The proposed AMDA method can surpass some traditional transfer learning fault diagnosis methods. Furthermore, as feature visualization result revealed, AMDA has significant advantages in multi-domain and broad research prospects.

Implantable neural electrodes can record and regulate neural activities with high spatial resolution of single-neuron and high time resolution of sub-millisecond, which are the most extensive window in neuroscience research. However, the mechanical mismatch between conventional stiff electrodes and soft neural tissue can lead to inflammatory responses and degradation of signals in chronic recordings. Although remarkable breakthroughs have been made in sensing and regulation of neural signals, the long-term stability and chronic inflammatory response of the neural electrode-tissue interfaces still needs further development. In this review, we focus on the latest developments for the optimization of neural electrode-tissue interfaces, including electrode materials (graphene fiber-based and CNT fiber-based), electrode structures (flexible electrodes), nano-coatings and hydrogel-based neural interfaces. The parameters of impedance, charge injection limit, signal-to-noise ratio and neuron lost zone are used to evaluate the electrochemical performance of the devices, the recording performance of biosignals and the stability of the neural interfaces, respectively. These optimization methods can effectively improve the long-term stability and the chronic inflammatory response of neural interfaces during the recording and modulation of biosignals.

Atomically precise Au

Background Chemo-resistance of bladder cancer has been considered to be one of the serious issues to be solved. In this study, we revealed pivotal role of miR-424 in the regulation of CDDP sensitivity of bladder cancer cells. Methods The cytotoxicity of cisplatin and effect of miR-424 were assessed by flow cytometry and TUNEL. Transcriptional regulation of miR-424 by HIF-1α was assessed by Chromatin immunoprecipitation (ChIP). Effect of miR-424 on expression of UNC5B, SIRT4 (Sirtuin4) and apoptotic markers was measured by QRT-PCR and/or Western blot. The regulation of miR-424 for UNC5B and SIRT4 were tested by luciferase reporter assay. The 5637-inoculated nude mice xenograft model was used for the in vivo study. The clinical significance of miR-424 was demonstrated mainly through data mining and statistical analysis of TCGA. Results In this study, we have found for the first time that cisplatin (CDDP) induces the expression of miR-424 in a HIF-1α-dependent manner under normoxia, and miR-424 plays a vital role in the regulation of CDDP resistance of bladder cancer cells in vitro. Mechanistically, we have found that UNC5B and SIRT4 are the direct downstream target genes of miR-424. CDDP-mediated suppression of xenograft bladder tumor growth was prohibited by the addition of miR-424, whereas ectopic expression of UNC5B or SIRT4 partially restored miR-424-dependent decrease in CDDP sensitivity of bladder cancer 5637 and T24 cells. Moreover, knockdown of UNC5B or SIRT4 prohibited CDDP-mediated proteolytic cleavage of PARP and also decreased CDDP sensitivity of these cells. Consistently, the higher expression levels of miR-424 were closely associated with the poor clinical outcome of the bladder cancer patients. There existed a clear inverse relationship between the expression levels of miR-424 and pro-apoptotic UNC5B or SIRT4 in bladder cancer tissues. Conclusions Collectively, our current results strongly suggest that miR-424 tightly participates in the acquisition/maintenance of CDDP-resistant phenotype of bladder cancer cells through down-regulation of its targets UNC5B and SIRT4, and thus combination chemotherapy of CDDP plus HIF-1α/miR-424 inhibition might have a significant impact on hypoxic as well as normoxic bladder cancer cells.

Background Small compound oridonin acts as an effective anti-tumor agent used for a wide variety of human malignancies, while the antitumor efficacy and molecular mechanism of oridonin against bladder cancer remains unclear. Methods Four independent cohorts of bladder cancer were employed to assess the correlation between netrin-1 expression and progression and prognosis of bladder cancer. Clinical potential of netrin-1 as a biomarker and oridonin-mediated netrin-1-targeting anti-tumor mechanism were investigated by QRT-PCR, Western blot and ELISA. Regulatory mechanisms of Netrin-1 were investigated by luciferase reporter assay and Western blot. The EJ-inoculated nude mice xenograft model was used for the in vivo study. Results High expression of netrin-1 was significantly correlated with a poor overall survival in three independent bladder cancer cohorts. Urinary netrin-1 level was significantly elevated in bladder cancer patients correlating with tumor invasion and grade. Netrin-1 promoted cell proliferation, tumorsphere-forming, migration and invasion in bladder cancer cells. Oridonin treatment strikingly suppressed these malignant phenotypes and induced cell death in TCC cell lines and murine xenografts. Oridonin markedly decreased netrin-1 through inhibiting NF-κB transcriptional activity and shortening the half-life of NTN1 mRNA via inducing IRE1α, resulting in repression of its downstream signaling. Conclusions Together, these results strongly suggest that netrin-1 promotes the progression of bladder cancer, and acts as a potential urinary biomarker for the diagnosis as well as the prediction of the tumor progression. Oridonin exerts its strong anti-tumor activity against the invasive bladder cancer by suppressing netrin-1 mRNA production and stability.

Additional file 1: Supplementary Table 1. Sequences of oligonucleotide primers used for qPCR in the study. Supplementary Table 2. Clinicopathological characters of the patients with bladder cancer in our dataset.

Mechanical fault diagnosis is an indispensable part of the modern industrial production process. The application scenario of fault diagnosis according to a neural network from theory to practical application is worth exploring. Most existing work focuses on remaining life prediction and fault classification, treating these two steps independently. This study aims at coherent real-time monitoring of bearing status and proposes a gated recurrent unit -based fault monitoring structure to obtain timely response and preliminary classification of sudden faults. In the existing fault classification research, more attention is paid to the classification accuracy of the fault details. The time sequence law followed by the sudden fault and the short-term prediction of that fault are easily overlooked. The proposed method is trained by key-frames of bearing data. These data frames first pass through the feature extraction layer which consists of two layers of 1D convolution. Then, the reset gates and update gates of developed units keep the valid information at the last moment and update the unit state at that instant. A sudden fault will trigger the detection network, and the detected fault frame will be extracted for further classification by the independently trained fault classification network. During the test, a prediction of the moment of failure occurrence is directly obtained. When the status is judged to be faulty, the fault frame is directly extracted and used as the input of the classification network. Experimental results confirm that the network quickly responds to sudden failures under an operating environment, and the classification accuracy rate can stably reach more than 98%.

In this work, the organic light-emitting diodes (OLEDs) based on Alq3 are fabricated. In order to make clear the transport mechanism of carriers in organic light-emitting devices at low temperature, detailed electroluminescence transient response and the current-voltage–luminescence (I–V–L) characteristics under different temperatures in those OLEDs are investigated. It founds that the acceleration of brightness increases with increasing temperature is maximum when the temperature is 200 K and it is mainly affected by the electron transport layer (Alq3). The MoO3 injection layer and the electroluminescent layer have great influence on the delay time when the temperature is 200 K. Once the temperature is greater than 250 K, the delay time is mainly affected by the MoO3 injection layer. On the contrary, the fall time is mainly affected by the electroluminescent material. The Vf is the average growth rate of fall time when the temperature increases 1 K which represents the accumulation rate of carriers. The difference between Vf caused by the MoO3 injection layer is 0.52 us/K and caused by the electroluminescent material Ir(ppy)3 is 0.73 us/K.

This paper studies the aerodynamic characteristics of the composite motion of the wing during the flight of the bionic flapping wing. The dynamic hybrid mesh technique is used to solve the Nave Stokes (N-S) equation, and the changes of the lift resistance generated by the wing under different flapping amplitude, flapping frequency and chord torsion angle parameters are analyzed. By analyzing the aerodynamic efficiency of the wing, the optimal motion parameters of the flapping wing are obtained, which provides a theoretical basis for the design of the flapping bionic aircraft.

Mobile medical devices provide great promise for self-health monitoring and preventive medicine. Especially, photodetectors (PDs) based on two-dimensional (2D) materials have attracted the wide interest in biomedicine and healthcare. In this review, we summarized the research progress of PDs based on 2D materials, and described the important applications of these devices in the wearable and implantable devices. We also analyzed their various properties such as sensitivity, mechanical flexibility, robustness and biocompatibility of the wearable and implantable devices. The typical biomedical application, such as UV-radiation monitor, pulse oximeters and retinal prosthesis were reviewed. We also discussed some of the technical challenges in wearable and implantable device and possible solutions. The state of art, non-invasive devices show great promising for real-time pathological monitor, health management and tracking.

The fabrication of high-aspect-ratio metal micro device on metal substrate is largely limited by its poor interfacial adhesion strength between metal substrate and thick SU-8 photoresist mould. In this paper, ultrasonic treatment is introduced to improve the interfacial adhesion strength between metal substrate and a high-aspect-ratio inertial switch SU-8 mould. Firstly, a device for ultrasonic treatment was developed, ultrasonic vibration is applied to SU-8 film after post exposure baking in order to improve the interfacial adhesion strength. Compared with the traditional one, SU-8 photoresist mould treated by ultrasonic vibration can effectively improve the interfacial adhesion strength. After 90 min cavitation erosion test, SU-8 film treated by ultrasonic vibration remains 34.4% relative to nothing left of the SU-8 film without ultrasonic treatment. Besides, the mechanisms of ultrasonic treatment on improving interfacial adhesion strength are investigated. Finally, an inertial switch is successfully fabricated on metallic substrate with the ultrasonic treated SU-8 photoresist mould.

Hexokinase (HK) plays a key role in various biological processes such as glycolysis of tumor cells. However, there is still a lack of systematic understanding of the contribution of HK family genes in different types of cancer. In the present study, we systematically analyzed the molecular changes and clinical correlations of HK family genes in 33 types of cancer extracted from more than 10,000 subjects. As a result, there were extensive genetic changes in HK family genes and the expression levels of HK family were significantly correlated with the activity of cancer marker-related pathways. In addition, HK family genes may be useful in predicting prognosis and therapeutic efficacy. Moreover, HK1,HK2 and HK3 may become potential oncogenes across a variety of cancer types. Furthermore, the oncogenic functions of HK1 in bladder cancer have been confirmed in vitro. Collectively, our results provide valuable resources to guide the mechanism and therapeutic analysis concerning the role of HK family genes in cancer.

Micro inertial switches are widely used in airbags, accessories and military weapons. SU-8 photoresist and electroforming based UV-LIGA process is an effective way to fabricate inertial switches. However, during the fabrication, the high stress in the SU-8 layers often causes them to detach from the substrate, which results in fabrication failure. To solve the detachment problem of SU-8 layers, a novel method was presented in this paper to release the internal stress in SU-8 layers by decreasing the area of electroforming layers. ANSYS simulation study was performed to verify the stress reduction effect of this method. The simulation and experiment results showed that stress in SU-8 layers can be reduced effectively. By using this method, a multi-scale inertial switch with ultra-high aspect ratio 17:1 was fabricated successfully. The overall size of the inertial switch is 14 × 11 × 0.6 mm. The inertial switch is fabricated by multi-layer UV-LIGA process. Fabrication error of the process is estimated in this paper. The stress reduction method and error estimate method presented in this paper can provide help to the fabrication of micro metal devices with large area and high aspect ratio.

Micro-cantilever has shown wide application prospect in the field of micro-sensors, actuators, gyroscope, and so on. There are abundant research studies on simple cantilever beam models, but there are few on S-shaped folding cantilever with complex structure, although it is widely used. In order to study the deformation failure of S-shaped folding cantilever, the force analysis of S-shaped folding cantilever was carried out in this article, and the stress values of different positions under the external load of the cantilever were deduced. The finite element model about S-shaped folding cantilever was built based on software ANSYS. The theoretical calculation was compared with the finite element calculation, and the results showed that the max stress is 681 MPa based on the derived theoretical formula, the max stress is 673 MPa based on the ANSYS, the error is 1.18%, which can prove formula is accurate. To further validate the stress predicted by the mathematical modeling, a micro-force testing platform was built to test the cantilever. Since the stress value cannot be measured directly in the test, the force corresponding to the stress was taken as standard and compared it with the simulation. The tested external force was corresponding the yield limit. The results showed that the experimental force was 0.06462 N before the plastic deformation occurred, the theoretical outcome was 0.065231 N corresponding the yield limit, the error was 0.94%. Both simulation and experimental results depict that the theoretical model is effective for predicting the stress of the S-shaped folded cantilever. The theoretical model helps to enhance the efficiency, and improve the performance, predictability, and control of the S-shaped folding cantilever.

Numerical simulations of the unsteady aerodynamic characteristics of the flapping wing composite motion are performed. To avoid negative grid sizes arising with the use of a dynamic grid and leading to divergences in the simulation and to errors in the results, an overlapping nested grid is used for the flow field background, wing, and fuselage structure. The analysis is based on the Navier–Stokes equations (N-S) and the pressure–velocity coupling method, while spatial dispersion is handled using the second-order finite volume and the adaptive step size solving strategy. The lift and resistance generated by the wing for different combinations of flow velocity, flutter frequency and amplitude, and torsion angle are determined, and the aerodynamic efficiency and flow fields are compared to find the flapping parameters that give the best aerodynamic efficiency. The simulation results show that the aerodynamic lift of a flapping wing can be greatly increased by increasing the flapping frequency, while, for a fixed frequency, the lift can be further increased by increasing the flapping amplitude, although by only a small amount. Increasing the torsion angle in the flapping of the wing can also increase the lift, but the aerodynamic efficiency will be reduced if this angle is too large. Thus, an appropriate selection of flapping wing motion parameters can effectively increase the flight lift and improve the aerodynamic efficiency.

In this paper, a novel MEMS-based switch is designed and characterized for the purpose of sensing the low g acceleration and output on-off signa1. The switch consists of an annular proof-mass suspended by helix spring that is fixed to the pedestal which located in center and connected with the bottom glass cover. The characteristic of the helix spring decides that the switch can sense the weak signal. The dynamic modeling of the design is obtained using finite element method (FEM) in the commercial code ANSYS. To verify the sensitivity and the reliability of the switch, the impact process is simulated, and the response time is calculated. The results show that the response time is short enough, the helix spring presents elastic deformation, and the switch can be used time after time. The modal analysis of the switch is carried out using finite element method in the case of constrained model, the inherent frequencies and mode shapes of the first 4 order modes are obtained respectively, and the analysis result gives a reference for switch design and us.

For single non-uniform surface compound eyes cannot achieve zoom imaging, resulting in poor imaging and other issues, a new type of aspherical artificial compound eye structure with variable focal length is proposed in this paper. The structure divides the surface compound eye into three fan-shaped areas, and different focal lengths of the micro-lens in different area make the artificial compound eye zoom in a certain range. The focal length and size of the micro-lens are determined by the area and the location of the micro-lens. The optimization of aspherical array of the micro-lens is calculated and the spherical aberration in each area is reduced to one percent of the initial value. Through simulation analysis, the designed artificial compound eye structure can realize the focal length adjustment, and effectively reduce the problem of the poor imaging quality of the curved compound eye edge. As a result, the aspherical artificial compound eye sample with the number of eyes of n=61 and the diameter of the base of 8.66mm was prepared using the molding method. The mutual relationship between the eyes of the child was calibrated and a mathematical model for the simultaneous identification of multiple sub eyes was established. An artificial compound eye positioning experimental system with the error value less than 10% was set up through a number of micro-lens capture target point settlement coordinates.

The Omni-directional impact MEMS switch was designed and characterized for the purpose of impact sensing. In order to turn on the circle reliably, the connect time should be long enough, the structure of flexible electrode was designed to extend the holding time. The structure consists of electrode A and B, electrode A is the sensing mass simultaneously, the sensing mass is suspended by helix cantilever that is fixed to the pedestal, the outer ring is the electrode B, which is suspended by helix cantilever that is fixed to the outer frame. Between the two electrodes, there is a gap, the gap separates electrode A and B, thereby keeping the switch in the open state. The distortion during the impact process extended the contact time. The dynamics of the switch is simulated, the simulation results show that the response time of the switch is 0.135ms, it is short enough, and the contact time which is also called holding time is about 20, the extended time make the switch turn on more reliably. These results satisfy the required specifications for the ammunition systems. DOI: http://dx.doi.org/10.11591/telkomnika.v11i5.2473

This article summarizes research on a novel, two-direction impact acceleration switch. To sense the change of two direction impact acceleration, A MEMS impact acceleration switch with two sensitive directions was designed. In this design, four serpentine springs were used to fix and suspend the movable electrode (sensing mass). The motion of the sensing mass was investigated by theoretical analysis and finite element analysis (FEA). To investigate whether the serpentine springs’ intensity was enough, the switch of the 1500g threshold acceleration in y direction and the 800g threshold acceleration in x direction was designed, simulated with Covent or Ware respectively. The simulation showed that the threshold accelerations basically fulfill the expectancy. To ensure the unintentional vibration inputs would not drive the sensor mass to the fixed electrode, the mode of the switch was analyzed and its natural frequency and the corresponding mode shapes were obtained from the calculation.

In this paper, a novel MEMS inertial switch is designed and characterised for the purpose of crash sensing for ammunition systems in which high-speed response is required for triggering the detonator. In order to keep the same sensitivity in different direction, the structure of an annular proof-mass suspended by four serpentine flexures is designed. The motion of the inertial switch is analysed by dynamic simulation, the simulation results show that the response time is 0.142 ms and the contact time of the switch is about 5 us under the 700 g threshold acceleration. It illustrates that the response time is short enough and the impact time satisfy the ask. The von-mises stress of the structure is calculate, the maximum stress occurs in the serpentine flexures, the value is 60.61 MPa, much less than the yield strength of the silicon, the switch can be used time after time. The static behaviour of the serpentine flexures is researched, and the width of the serpentine flexure is determined as the most important factor to the threshold acceleration. With the width of the serpentine flexure increasing, the threshold of the switch will increase, and the response time of the inertial switch will decrease.