Characterizing the Coefficient of Friction Between a Capsule Robot and the Colon.

OBJECTIVE: A capsule robot (CR) with an onboard active locomotion mechanism, has been developed as a promising alternative to colonoscopy due to its minimally-invasive advantage. Predicting the traction force and locomotion resistance of the CR, which are both the friction force, is significantly important for the CR development and control. However, a comprehensive study concerning the coefficient of friction (COF) in the colon, which is necessary for prediction, is not available in literature. This paper is dedicated to determining a quantitative COF equation in terms of the contact pressure, hoop strain, and sliding velocity. METHODS: The COFs of three commonly-used materials of the CR (i.e., PDMS, white and transparent ABS plastic), are measured under 144 different friction cases (6 contact pressures×4 hoop strains×6 sliding velocities). By analyzing the measurements, the influence law of the three factors on the COFs of the three materials is revealed, and based on which, a general COF equation involving eight fitted constants is determined. RESULTS: The determination coefficients of the COF equation for the three materials are up to 0.9822, 0.9286, and 0.9696, respectively. The COF equation is used to predict the traction force and locomotion resistance of a crawler CR, and the predicting results fit well with the measured ones. CONCLUSION: The COF equation can provide a correct COF for friction force prediction. SIGNIFICANCE: It is promising to enable a better force and locomotion control for the CR in the colon.

Laser-upgraded coal tar for smart pavements in road and bridge monitoring applications.

The implementation of an intelligent road network system requires many sensors for acquiring data from roads, bridges, and vehicles, thereby enabling comprehensive monitoring and regulation of road networks. Given this large number of required sensors, the sensors must be cost-effective, dependable, and environmentally friendly. Here, we show a laser upgrading strategy for coal tar, a low-value byproduct of coal distillation, to manufacture flexible strain-gauge sensors with maximum gauge factors of 15.20 and 254.17 for tension and compression respectively. Furthermore, we completely designed the supporting processes of sensor placement, data acquisition, processing, wireless communication, and information decoding to demonstrate the application of our sensors in traffic and bridge vibration monitoring. Our novel strategy of using lasers to upgrade coal tar for use as a sensor not only achieves the goal of turning waste into a resource but also provides an approach to satisfy large-scale application requirements for enabling intelligent road networks.

TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Increased DEF6 expression is correlated with metastasis and poor prognosis in human osteosarcoma.

Metastasis is the primary cause of high mortality in patients with osteosarcoma (OS). However, the molecular mechanisms underlying the regulation of metastatic disease are yet to be determined. Differentially expressed in FDCP 6 homolog (DEF6) has been demonstrated to be correlated with the metastatic behavior of several cancers, such as breast, ovarian and colorectal cancers. However, the role of DEF6 in OS remains unknown. Accordingly, the current study aimed to investigate the relationship between DEF6 expression and the malignant behavior of OS. The results revealed that high levels of DEF6 in OS tissues were associated with advanced clinical stage and metastases. Furthermore, immunohistochemistry results predicted a poor prognosis in 58 human OS specimens. Additionally, DEF6 expression was reported to be upregulated in human OS cell lines compared with a normal osteoblast cell line. small interfering RNA transfection, cell proliferation and colony formation assays, wound healing assays and Transwell assays were performed. DEF6 was not identified to be a major driver of OS cell proliferation, but it significantly contributed to metastatic potential in vitro. In addition, bioinformatics, western blotting and immunohistochemistry results indicated that MMP9 expression was positively correlated with DEF6 expression in human OS. To summarize, the results revealed that increased levels of DEF6 were associated with metastasis and poor prognosis in human OS and that DEF6 expression is positively correlated with MMP9 expression. The results indicated that DEF6 may serve as a potential antimetastatic target for OS.

Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma.

Background and Purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens. Materials and Methods: Paired tumor samples were collected from 10 patients with non-small cell lung cancer (NSCLC) or lung metastatic carcinoma within a week before and after SBRT. DNA and RNA of tumor tissues was extracted from the paired samples. Whole-exome and RNA sequencing assays were performed by next-generation sequencing. Gene mutation, genomic expression, T-cell receptor (TCR) repertoire, and profiling of tumor-infiltrating immune cells were analyzed through bioinformatics analysis in paired tumor samples. CD8+ T-cell infiltration and PD-L1 expressions were detected by immunostaining in tumor tissues. Results: The diversity of TCR repertoire and PD-L1 expression increased significantly in the TME, and the most enriched term of the gene ontology analysis was the immune response gene after receiving SBRT. SBRT induced neo-mutation of genes in tumor cells but did not increase tumor mutation burden in tumor tissues. TME displayed complex immune cell changes and infiltration and expression of immune-regulating factors such as C-X-C motif chemokine (CXCL) 10, CXCL16, interferons (IFNs), and IFN receptors. CD8+ T-cells in tumor tissues did not improve significantly after SBRT while the infiltrating TH1 and TH2 cells decreased remarkably. Conclusion: SBRT improved the TCR repertoire diversity and PD-L1 expression in the TME and induced neo-mutation of genes in tumor cells but did not increase CD8+ T-cell infiltration and IFN expression in the tumor tissue within a week.

High expression of ID1 facilitates metastasis in human osteosarcoma by regulating the sensitivity of anoikis via PI3K/AKT depended suppression of the intrinsic apoptotic signaling pathway.

A lack of understanding of the molecular basis underlying the regulation of metastatic disease and its effective therapy are the primary causes of high mortality in osteosarcoma. Thus, new insights into metastases and novel effective targets for metastatic osteosarcoma are urgently required. Anoikis resistance is considered a hallmark of cancer cells with metastatic ability. However, the molecular mechanism of anoikis is poorly understood in osteosarcoma. We applied immunohistochemistry to investigate the correlation between inhibitor of differentiation or DNA binding 1 (ID1) and clinicopathological features, and investigated the correlation between ID1 and the metastatic behavior of osteosarcoma cells, in vitro and in vivo. The results revealed that ID1 is overexpressed in human osteosarcoma tissues, is positively associated with lung metastases, and is a potential biomarker of poor prognosis. Overexpression of ID1 could increase anoikis insensitivity of osteosarcoma cells to facilitate metastasis through the PI3K/AKT-dependent mitochondrial apoptosis pathway. Knockdown of ID1 partly reversed the high potential of metastasis in anoikis-resistant osteosarcoma cells. Our findings revealed, that ID1 is a candidate molecular target for metastatic potential osteosarcoma by highlighting the role of anoikis resistance. In addition ID1 might be a potential predictor of poor prognosis in patients with osteosarcoma.

A Room-Temperature CNT/Fe3O4 Based Passive Wireless Gas Sensor.

A carbon nanotube/Fe3O4 thin film-based wireless passive gas sensor with better performance is proposed. The sensitive test mechanism of LC (Inductance and capacitance resonant) wireless sensors is analyzed and the reason for choosing Fe3O4 as a gas sensing material is explained. The design and fabrication process of the sensor and the testing method are introduced. Experimental results reveal that the proposed carbon nanotube (CNT)/Fe3O4 based sensor performs well on sensing ammonia (NH3) at room temperature. The sensor exhibits not only an excellent response, good selectivity, and fast response and recovery times at room temperature, but is also characterized by good repeatability and low cost. The results for the wireless gas sensor's performance for different NH3 gas concentrations are presented. The developed device is promising for the establishment of wireless gas sensors in harsh environments.

An LC Passive Wireless Gas Sensor Based on PANI/CNT Composite.

This paper proposes a wireless passive gas sensor based on the principle of LC mutual coupling. After the acidification of the carbon nanotube (CNT), the in-situ polymerization of the aminobenzene monomers was conducted on the surface of the acidified CNT to form a sensitive material composed of a polyaniline/carbon nanotube (PANI/CNT) composite. The Advanced Design System (ADS) software was used for simulating and analyzing the designed structure, which obtained the various parameters of the structure. A lead-free aluminum paste was printed on an alumina ceramic substrate via the screen printing technique to form an inductor coil, before the gas sensitive material was applied to prepare a wireless passive gas sensor, consisting of a single-turn inductor and interdigitated electrodes on the base structure. Finally, an experimental platform was built to test the performance of the sensor. The sensitivity of the gas sensor is about 0.04 MHz/ppm in an atmosphere with a NH3 concentration of 300 ppm. The sensor was shown to have good repeatability and high stability over a long time period.

TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis.

BACKGROUND: Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear. METHODS: We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing. RESULTS: We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models. CONCLUSIONS: Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

A simplified sheathless cell separation approach using combined gravitational-sedimentation-based prefocusing and dielectrophoretic separation.

Prefocusing of the cell mixture is necessary for achieving a high-efficiency and continuous dielectrophoretic (DEP) cell separation. However, prefocusing through sheath flow requires a complex and tedious peripheral system for multi-channel fluid control, hindering the integration of DEP separation systems with other microfluidic functionalities for comprehensive clinical and biological tasks. This paper presented a simplified sheathless cell separation approach that combines gravitational-sedimentation-based sheathless prefocusing and DEP separation methods. Through gravitational sedimentation in a tubing, which was inserted into the inlet of a microfluidic chip with an adjustable steering angle, the cells were focused into a stream at the upstream region of a microchannel prior to separation. Then, a DEP force was applied at the downstream region of the microchannel for the active separation of the cells. Through this combined strategy, the peripheral system for the sheath flow was no longer required, and thus the integration of cell separation system with additional microfluidic functionalities was facilitated. The proposed sheathless scheme focused the mixture of cells with different sizes and dielectric properties into a stream in a wide range of flow rates without changing the design of the microfluidic chip. The DEP method is a label-free approach that can continuously separate cells on the basis of the sizes or dielectric properties of the cells and thus capable of greatly flexible cell separation. The efficiency of the proposed approach was experimentally assessed according to its performance in the separation of human acute monocytic leukemia THP-1 cells from yeast cells with respect to different sizes and THP-1 cells from human acute myelomonocytic leukemia OCI-AML3 cells with respect to different dielectric properties. The experimental results revealed that the separation efficiency of the method can surpass 90% and thus effective in separating cells on the basis of either size or dielectric property.

Microwave Backscatter-Based Wireless Temperature Sensor Fabricated by an Alumina-Backed Au Slot Radiation Patch.

A wireless and passive temperature sensor operating up to 800 °C is proposed. The sensor is based on microwave backscatter RFID (radio frequency identification) technology. A thin-film planar structure and simple working principle make the sensor easy to operate under high temperature. In this paper, the proposed high temperature sensor was designed, fabricated, and characterized. Here the 99% alumina ceramic with a dimension of 40 mm × 40 mm × 1 mm was prepared in micromechanics for fabrication of the sensor substrate. The metallization of the Au slot patch was realized in magnetron sputtering with a slot width of 2 mm and a slot length of 32 mm. The measured resonant frequency of the sensor at 25 °C is 2.31 GHz. It was concluded that the resonant frequency decreases with the increase in the temperature in range of 25-800 °C. It was shown that the average sensor sensitivity is 101.94 kHz/°C.

Characterization of biomechanical properties of cells through dielectrophoresis-based cell stretching and actin cytoskeleton modeling.

BACKGROUND: Cytoskeleton is a highly dynamic network that helps to maintain the rigidity of a cell, and the mechanical properties of a cell are closely related to many cellular functions. This paper presents a new method to probe and characterize cell mechanical properties through dielectrophoresis (DEP)-based cell stretching manipulation and actin cytoskeleton modeling. METHODS: Leukemia NB4 cells were used as cell line, and changes in their biological properties were examined after chemotherapy treatment with doxorubicin (DOX). DEP-integrated microfluidic chip was utilized as a low-cost and efficient tool to study the deformability of cells. DEP forces used in cell stretching were first evaluated through computer simulation, and the results were compared with modeling equations and with the results of optical stretching (OT) experiments. Structural parameters were then extracted by fitting the experimental data into the actin cytoskeleton model, and the underlying mechanical properties of the cells were subsequently characterized. RESULTS: The DEP forces generated under different voltage inputs were calculated and the results from different approaches demonstrate good approximations to the force estimation. Both DEP and OT stretching experiments confirmed that DOX-treated NB4 cells were stiffer than the untreated cells. The structural parameters extracted from the model and the confocal images indicated significant change in actin network after DOX treatment. CONCLUSION: The proposed DEP method combined with actin cytoskeleton modeling is a simple engineering tool to characterize the mechanical properties of cells.

Acetone Sensing Properties of a Gas Sensor Composed of Carbon Nanotubes Doped With Iron Oxide Nanopowder.

Iron oxide (Fe2O3) nanopowder was prepared by a precipitation method and then mixed with different proportions of carbon nanotubes. The composite materials were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. A fabricated heater-type gas sensor was compared with a pure Fe2O3 gas sensor under the influence of acetone. The effects of the amount of doping, the sintering temperature, and the operating temperature on the response of the sensor and the response recovery time were analyzed. Experiments show that doping of carbon nanotubes with iron oxide effectively improves the response of the resulting gas sensors to acetone gas. It also reduces the operating temperature and shortens the response recovery time of the sensor. The response of the sensor in an acetone gas concentration of 80 ppm was enhanced, with good repeatability.

High-Temperature Dielectric Properties of Aluminum Nitride Ceramic for Wireless Passive Sensing Applications.

The accurate characterization of the temperature-dependent permittivity of aluminum nitride (AlN) ceramic is quite critical to the application of wireless passive sensors for harsh environments. Since the change of the temperature-dependent permittivity will vary the ceramic-based capacitance, which can be converted into the change of the resonant frequency, an LC resonator, based on AlN ceramic, is prepared by the thick film technology. The dielectric properties of AlN ceramic are measured by the wireless coupling method, and discussed within the temperature range of 12 °C (room temperature) to 600 °C. The results show that the extracted relative permittivity of ceramic at room temperature is 2.3% higher than the nominal value of 9, and increases from 9.21 to 10.79, and the quality factor Q is decreased from 29.77 at room temperature to 3.61 at 600 °C within the temperature range.

Erythrocytosis and pulmonary hypertension in a mouse model of human HIF2A gain of function mutation.

The central pathway for oxygen-dependent control of red cell mass is the prolyl hydroxylase domain protein (PHD):hypoxia inducible factor (HIF) pathway. PHD site specifically prolyl hydroxylates the transcription factor HIF-α, thereby targeting the latter for degradation. Under hypoxia, this modification is attenuated, allowing stabilized HIF-α to activate target genes, including that for erythropoietin (EPO). Studies employing genetically modified mice point to Hif-2α, one of two main Hif-α isoforms, as being the critical regulator of Epo in the adult mouse. More recently, erythrocytosis patients with heterozygous point mutations in the HIF2A gene have been identified; whether these mutations were polymorphisms unrelated to the phenotype could not be ruled out. In the present report, we characterize a mouse line bearing a G536W missense mutation in the Hif2a gene that corresponds to the first such human mutation identified (G537W). We obtained mice bearing both heterozygous and homozygous mutations at this locus. We find that these mice display, in a mutation dose-dependent manner, erythrocytosis and pulmonary hypertension with a high degree of penetrance. These findings firmly establish missense mutations in HIF-2α as a cause of erythrocytosis, highlight the importance of this HIF-α isoform in erythropoiesis, and point to physiologic consequences of HIF-2α dysregulation.

Development of an optical gas leak sensor for detecting ethylene, dimethyl ether and methane.

In this paper, we present an approach to develop an optical gas leak sensor that can be used to measure ethylene, dimethyl ether, and methane. The sensor is designed based on the principles of IR absorption spectrum detection, and comprises two crossed elliptical surfaces with a folded reflection-type optical path. We first analyze the optical path and the use of this structure to design a miniature gas sensor. The proposed sensor includes two detectors (one to acquire the reference signal and the other for the response signal), the light source, and the filter, all of which are integrated in a miniature gold-plated chamber. We also designed a signal detection device to extract the sensor signal and a microprocessor to calculate and control the entire process. The produced sensor prototype had an accuracy of ±0.05%. Experiments which simulate the transportation of hazardous chemicals demonstrated that the developed sensor exhibited a good dynamic response and adequately met technical requirements.

Nanopore-based detection of circulating microRNAs in lung cancer patients.

MicroRNAs are short RNA molecules that regulate gene expression, and have been investigated as potential biomarkers because their expression levels are correlated with various diseases. However, detecting microRNAs in the bloodstream remains difficult because current methods are not sufficiently selective or sensitive. Here, we show that a nanopore sensor based on the α-haemolysin protein can selectively detect microRNAs at the single molecular level in plasma samples from lung cancer patients without the need for labels or amplification of the microRNA. The sensor, which uses a programmable oligonucleotide probe to generate a target-specific signature signal, can quantify subpicomolar levels of cancer-associated microRNAs and can distinguish single-nucleotide differences between microRNA family members. This approach is potentially useful for quantitative microRNA detection, the discovery of disease markers and non-invasive early diagnosis of cancer.