LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality worldwide. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in human cancers, including ESCC. However, the detailed mechanisms of lncRNAs in the regulation of ESCC progression remain incompletely understood. LUESCC was upregulated in ESCC tissues compared with adjacent normal tissues, which was associated with gender, deep invasion, lymph node metastasis, and poor prognosis of ESCC patients. LUESCC was mainly localized in the cytoplasm of ESCC cells. Knockdown of LUESCC inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistic investigation indicated that LUESCC functions as a ceRNA by sponging miR-6785-5p to enhance NRSN2 expression, which is critical for the malignant behaviors of ESCC. Furthermore, ASO targeting LUESCC substantially suppressed ESCC both in vitro and in vivo. Collectively, these data demonstrate that LUESCC may exerts its oncogenic role by sponging miR-6785-5p to promote NRSN2 expression in ESCC, providing a potential diagnostic marker and therapeutic target for ESCC patients.

CircHIPK3 regulates fatty acid metabolism through miR-637/FASN axis to promote esophageal squamous cell carcinoma.

The oncogenic role of circRNA in cancers including esophageal cancer (EC) has been well studied. However, whether and how circRNAs are involved in cancer cell metabolic processes remains largely unknown. Here, we reported that circRNA, circHIPK3, is highly expressed in ESCC cell lines and tissues. Knockdown of circHIPK3 significantly restrained cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, circHIPK3 was found to act as a ceRNA by sponging miR-637 to regulate FASN expression and fatty acid metabolism in ESCC cells. Anti-sense oligonucleotide (ASO) targeting circHIPK3 substantially inhibited ESCC both in vitro and in vivo. Therefore, these results uncover a modulatory axis constituting of circHIPK3/miR-637/FASN may be a potential biomarker and therapeutic target for ESCC in the clinic.

miR-1301-3p promotes invasion and migration and EMT progression in esophageal cancer by downregulating NBL1 expression.

BACKGROUND: Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. MicroRNA-1301-3p (miR-1301-3p) plays vital roles in a majority of malignancies. The aim of this study was to investigate the role of miR-1301-3p/NBL1 axis on ESCA cell invasion, migration, epithelial-mesenchymal transition (EMT) process, as well as its association with prognosis of ESCA patients. METHODS: The expression levels of miR-1301-3p and NBL1 were predicted by bioinformatics and further verified by RT-qPCR assays. Kaplan-Meier (K-M) plotter analysis and univariate and multivariate Cox analyses were used to evaluate the relationship between miR-1301-3p and clinicopathological variables and prognosis. The role of miR-1301-3p on cell invasion, migration was detected by transwell invasion, and wound healing assays, respectively. The EMT-related proteins were detected by western blot. The target genes and the target binding sites were predicted by bioinformatics and further determined by RT-qPCR assay. RESULTS: MiR-1301-3p was remarkably upregulated in ESCA tissues and cells, and its high expression was associated with poor prognosis of ESCA. Overexpression of miR-1301-3p promoted ESCA cell invasion, migration and mediated EMT process in vitro, whereas knockdown of miR-1301-3p showed the opposite effects. Moreover, NBL1 was predicted as a target gene of miR-1301-3p. NBL1 was lowly expressed in ESCA cells and significantly decreased after upregulation of miR-1301-3p. Meanwhile, we found that low expression of NBL1 was significantly associated with poor prognosis of ESCA patients. CONCLUSION: MiR-1301-3p is a potential biomarker for predicting the prognosis of ESCA patients. It may promote ESCA invasion, migration and EMT progression by regulating NBL1 expression.

Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation.

Excessive melanin deposition may lead to a series of skin disorders. The production of melanin is carried out by melanocytes, in which the enzyme tyrosinase performs a key role. In this work, we identified a series of novel tyrosinase inhibitor hybrids with a dihydrochalcone skeleton and resorcinol structure, which can inhibit tyrosinase activity and reduce the melanin content in the skin. Compound 11c possessed the most potent activity against tyrosinase, showing IC50 values at nanomolar concentration ranges, along with significant antioxidant activity and low cytotoxicity. Furthermore, in vitro permeation tests, supported by HPLC analysis and 3D OrbiSIMS imaging visualization, revealed the excellent permeation of 11c. More importantly, compound 11c reduced the melanin content on UV-induced skin pigmentation in a guinea pig model in vivo. These results suggest that compound 11c may serve as a promising potent tyrosinase inhibitor for the development of a potential therapy to treat skin hyperpigmentation.

Crack detection for concrete bridges with imaged based deep learning.

Within the framework of intelligent bridge detection, a number of crack detection methods based on image processing techniques have been implemented. In this study, a combined novel approach with deep learning of a single shot multibox detector (SSD) and the eight neighborhood algorithm is proposed and applied to bridge crack image identification to provide an automatic method for crack detection. First, a large number of concrete crack images collected from the site were segmented and preprocessed for the establishment of a crack image dataset. Deep learning of the SSD algorithm was introduced on the training set to establish the detection model, where the model parameters were adjusted by the validation set. Sliding window technology was integrated to identify the cracks in the test set. The effects of the sliding window size and dataset size on the crack detection results were discussed. Moreover, the eight neighborhood algorithm was adopted for further crack detection correction. The results show that the configuration achieves good crack detection by the deep learning of the SSD algorithm with high precision and recall. The introduction of the eight neighborhood correction algorithm further improves the detection results by eliminating some misjudged results. Finally, the developed algorithm was placed into a portable device, with which cracks were effectively identified. The introduced method shows significantly better performance in crack detection, and the system installed on the portable device provides a way to broaden its application in the automatic crack detection of concrete bridges.

Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown. METHODS: Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment. RESULTS: Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo. CONCLUSIONS: An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.

Identification of new potent anticancer derivatives through simplifying the core structure and modification on their 14- hydroxyl group from oridonin.

The natural product oridonin has the potential to be a broad-spectrum antineoplastic agent. To develop oridonin analogues with high potency, a series of novel oridonin analogues were designed and synthesized by removing the multiple hydroxyl groups of parent compound. The representative analogues 14, 19, and 26 exhibited potent anticancer effects against K562, MDA-MB-231, SMMC-7721, and MCF-7 cells. Further structural modification on their 14-OH generated more potent derivatives 16n, 21d, and 28d respectively, in which the IC50 value of compound 16n was 50-fold more potent than parent oridonin in K562 cells. Furthermore, compound 16n significantly induced the cell cycle arrest of K562 cells at the G2 phase and increased the fraction of apoptotic cells. Importantly, compounds 16n, 21d, and 28d exhibited good antitumor activities in H22 allograft mice in vivo. These results suggest that compounds 16n, 21d, and 28d deserve further development as promising candidates for the treatment of cancers.

Long-Range Displacement Meters Based on Chipped Circular Patch Antenna.

This paper presents a passive wireless long-range displacement sensor that is based on the circular patch antenna, and the detecting range of the sensor can be customized. The sensor consists of a chipped circular antenna with two opened rectangular windows, a substrate, and a ground plate with a sloping channel. No bonding between the antenna and the ground plate allows for the chipped antenna to slide along the sloping channel. The channel will drive the current flow on the plate once the chip is activated, increasing the effective electrical length and, consequently, decreasing the resonant frequency of the circular antenna. The sensing mechanism equates the measuring displacement to the relative movement of the antenna with respect to the ground that achieves the measurement of long-range displacement and, thus, the proposed sensor can avoid stress damage to the antenna due to excessive deformation. Three different range sensors were simulated in the the Ansoft high frequency structure simulator (HFSS). The results show that the resonance frequency of the antenna has a linear relationship with the varying chute depth beneath the chip. Three sensors were fabricated, and the experimental results also validated that the sensitivity of the sensor can be adjusted.

Knockdown of miR-183 Enhances the Cisplatin-Induced Apoptosis in Esophageal Cancer Through Increase of FOXO1 Expression.

BACKGROUND: As an important member of platinum-based chemotherapeutic drugs, cisplatin is effective and is commonly used in the treatment of esophageal cancer. However, repeated use of cisplatin usually causes severe side-effects on patients. Novel approaches should be explored to increase the sensitivity of cancer cells to cisplatin. METHODS: The expression level of miR-183 in esophageal cancer tissues and cell lines was measured by quantitative reverse transcriptase real-time PCR (qRT-PCR). The sensitivity of EC cell lines to cisplatin was evaluated by CCK-8 assay and flow cytometry. Luciferase reporter assay was used to confirm the association between miR-183 and FOXO1. The apoptosis pathway of EC cells was tested by Western blot assay. RESULTS: The expression level of miR-183 was increased in esophageal cancer patients' tumor tissues and esophageal cancer cell lines. However, knockdown of miR-183 was found to enhance the effect of cisplatin on inducing the apoptotic cell death of esophageal cancer cells. In the mechanism research, we proved that FOXO1 was the target of miR-183 in esophageal cancer cells. Inhibition of miR-183 increased the expression of FOXO1 to promote the expression of Bim and Noxa. As Bim and Noxa acted as key pro-apoptotic proteins in mitochondrial apoptosis, inhibition of miR-183 enhanced the cisplatin-induced apoptosis pathway in esophageal cancer. CONCLUSION: Knockdown of miR-183 enhanced the cisplatin-induced apoptosis in esophageal cancer through an increase of FOXO1 expression.

A Capacitively-Fed Inverted-F Antenna for Displacement Detection in Structural Health Monitoring.

This paper presents a capacitive displacement sensor based on a capacitively fed inverted-F antenna (CFIFA) for displacement detection. The sensor is composed of a grounded L-shape patch and a rectangular upper patch, forming a capacitor between them. The asymmetric dipole model is adopted to explain the frequency shift and current distribution of the proposed antenna sensor at its first-order resonance. The numerical simulation of the CFIFA using the Ansoft high-frequency structure simulator (HFSS) software is carried out to optimize the dimensional parameters, allowing the antenna to perform better. Two sets of CFIFAs are fabricated and tested for verification. Results show that the CFIFA has a good linear relationship between its first resonant frequency and the relative displacement, and is capable of a long range of displacement measuring.

Numerical and Experimental Verification of a Multiple-Variable Spatiotemporal Regression Model for Grout Defect Identification in a Precast Structure.

Due to the increased service life, environmental corrosion, unreasonable construction, and other issues, local defects inevitably exist in civil structures, which affect the structural performance and can lead to structural failure. However, research on grout defect identification of precast reinforced concrete frame structures with rebars spliced by sleeves faces great challenges owing to the complexity of the problem. This study presents a multiple-variable spatiotemporal regression model algorithm to identify local defects based on structural vibration responses collected using a sensor network. First, numerical simulations were carried out on precast beam-column connection models by comparing the identification results based on a single-variable regression model, two-variable spatial regression model, and two-variable spatiotemporal regression model; furthermore, a multiple-variable spatiotemporal regression model was proposed and robustness analysis of the damage indicator was carried out. Then, to explore the validity of the proposed method, a nondestructive vibration experiment was considered on a half-scaled, two-floor, precast concrete frame structure with column rebars spliced by defective grout sleeves. The results show that local defects were successfully identified based on a multiple-variable spatiotemporal regression model.

hsa_circRNA_100873 upregulation is associated with increased lymphatic metastasis of esophageal squamous cell carcinoma.

Circular RNAs (circRNAs) are a type of endogenous non-coding RNA with multiple binding sites that specifically bind to microRNAs (miRNAs) and serve an important role in cellular regulatory networks. Patients exhibit varying levels of lymphatic metastasis in a clinical setting. The present study investigated the association between circRNAs and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC). The tissue samples were divided into three groups, including early tumor stage associated with advanced nodal stage (T1 group), advanced tumor stage associated with early nodal stage (T2 group) and healthy esophageal epithelial tissues as the control group (C group). Gene chip analysis identified circRNAs, and those with possible regulatory functions were validated by reverse transcription-quantitative polymerase chain reaction analysis (RT-qPCR). circRNAs containing miRNA response element (MRE) sequences were obtained, and circRNA/miRNA prediction software was used to predict miRNAs that may interact with circRNA. A total of 12,275 circRNAs were detected, including 861 with statistically significant differences. A comparison between the T1 and C groups identified 152 upregulated circRNAs and 431 downregulated ones, while a comparison between the T2 and C groups identified 187 upregulated and 481 downregulated circRNAs. A T1/T2 group comparison revealed that four circRNAs were upregulated and seven were downregulated (fold change >1.5; P<0.05). The RT-qPCR data and gene chip analysis consistently identified hsa_circRNA_100873 as differentially expressed among the examined groups. A total of five potential MREs and complementary sequences were selected for hsa_circRNA_100873. The results of the present study indicated that multiple differentially expressed circRNAs are involved in the pathogenesis of ESCC, and that upregulation of hsa_circRNA_100873 may be associated with increased lymphatic metastases in ESCC.

A Passive Wireless Crack Sensor Based on Patch Antenna with Overlapping Sub-Patch.

Monolithic patch antennas for deformation measurements are designed to be stressed. To avoid the issues of incomplete strain transfer ratio and insufficient bonding strength of stressed antennas, this paper presents a passive wireless crack sensor based on an unstressed patch antenna. The rectangular radiation patch of the proposed sensor is partially covered by a radiation sub-patch, and the overlapped length between them will induce the resonate frequency shift representing the crack width. First, the cavity model theory is adopted to show how the resonant frequencies of the crack sensor are related to the overlapped length between the patch antenna and the sub-patch. This phenomenon is further verified by numerical simulation using the Ansoft high-frequency structure simulator (HFSS), and results show a sensitivity of 120.24 MHz/mm on average within an effective measuring range of 1.5 mm. One prototype of proposed sensor was fabricated. The experiments validated that the resonant frequency shifts are linearly proportional to the applied crack width, and the resolution is suitable for crack width measuring.

A Displacement Sensor Based on a Normal Mode Helical Antenna.

This paper presents a passive displacement sensor based on a normal mode helical antenna. The sensor consists of an external helical antenna and an inserting dielectric rod. First, the perturbation theory is adopted to demonstrate that both the electric intensity and magnetic intensity have a noticeable gradient change within the in-and-out entrance of the helical antenna, which will cause the sensor to experience a resonant frequency shift. This phenomenon was further verified by numerical simulation using the Ansoft high frequency structure simulator (HFSS), and results show the linear correlation between the retrieved resonant frequency and the displacement. Two sets of proposed sensors were fabricated. The experiments validated that the resonant frequency shifts are linearly proportional to the applied displacement, and the sensing range can be adjusted to accommodate the user's needs.

Expression and significance of c-kit and epithelial-mesenchymal transition (EMT) molecules in thymic epithelial tumors (TETs).

BACKGROUND: To investigate the expression and significance of c-kit and epithelial-mesenchymal transition (EMT) molecules (E-cadherin, N-cadherin, Twist, Snail) in thymic epithelial tumors (TETs). METHODS: The tissue microarray technology and immunohistochemistry MaxVisionTM-use kit were used to detect the expression of c-kit and EMT molecular markers in 150 cases of paraffin sections of TET tissue and analysis the correlation between c-kit and EMT molecules and explore the malignancy and the relationship of clinicopathological parameters between c-kit, EMT molecules and TETs. RESULTS: The expression difference of c-kit and EMT molecular markers (E-cadherin, N-cadherin, Snail, Twist) in TETs subtypes was statistically significant (P<0.01) and their positive expression rate of thymic carcinoma was significantly higher than that in thymoma, and the difference was statistically significant, respectively (P<0.01). There is a negative correlation between the expression of c-kit and E-cadherin as well as a positive correlation between the expression level of c-kit, N-cadherin, Twist, and Snail. Furthermore, E-cadherin was negatively correlated with N-cadherin, Twist, and Snail while N-cadherin expression was positively correlated with Twist, Snail. CONCLUSIONS: Five indicators (c-kit, E-cadherin, N-cadherin, Twist, and Snail) may determine the malignancy of TETs, especially for distinguishing thymoma and thymic carcinoma.

In vivo biocompatibility and mechanical properties of porous zein scaffolds.

In our previous study, a three-dimensional zein porous scaffold with a compressive Young's modulus of up to 86.6+/-19.9 MPa and a compressive strength of up to 11.8+/-1.7 MPa was prepared, and was suitable for culture of mesenchymal stem cells (MSCs) in vitro. In this study, we examined its tissue compatibility in a rabbit subcutaneous implantation model; histological analysis revealed a good tissue response and degradability. To improve its mechanical property (especially the brittleness), the scaffolds were prepared using the club-shaped mannitol as the porogen, and stearic acid or oleic acid was added. The scaffolds obtained had an interconnected tubular pore structure, 100-380 microm in pore size, and about 80% porosity. The maximum values of the compressive strength and modulus, the tensile strength and modulus, and the flexural strength and modulus were obtained at the lowest porosity, reaching 51.81+/-8.70 and 563.8+/-23.4 MPa; 3.91+/-0.86 and 751.63+/-58.85 MPa; and 17.71+/-3.02 and 514.39+/-19.02 MPa, respectively. Addition of 15% stearic acid or 20% oleic acid did not affect the proliferation and osteogenic differentiation of MSCs, and a successful improvement of mechanical properties, especially the brittleness of the zein scaffold could be achieved.

Mechanical properties and in vitro biocompatibility of porous zein scaffolds.

A porous scaffold utilizing hydrophobic protein zein was prepared by the salt-leaching method for tissue engineering. The scaffolds possessed a total porosity of 75.3-79.0%, compressive Young's modulus of (28.2+/-6.7)MPa-(86.6+/-19.9)MPa and compressive strength of (2.5+/-1.2)MPa-(11.8+/-1.7)MPa, the percentage degradation of 36% using collagenase and 89% using pepsin during 14 days incubation in vitro. The morphology of pores located on the surface and within the porous scaffolds showed good pore interconnectivity by scanning electron microscopy (SEM). Rat mesebchymal stem cells (MSCs) could adhere, grow, proliferate and differentiate toward osteoblasts on porous zein scaffold. With the action of dexamethasone, the cells showed a relative higher activity of alkaline phosphatase (ALP) and a higher proliferating activity (p<0.05) than those of MSCs without dexamethasone.

A novel porous natural polymer scaffold for tissue engineering.

UNLABELLED: A novel porous polymer scaffold fabricated by salt-leaching method for tissue engineering was developed and the mechanical properties and porosity were investigated in our study. Scanning electronic microscopy (SEM) was employed to observe the morphology and structure of porous scaffolds. Cytocompatility of the porous scaffolds were evaluated, using HL-7702 cells as model, in terms of cell attachment and cell viabilities from 3 to 72 hours determined by MTT method. RESULT: These scaffolds possessed a total porosity of 64.2%, compressive Young's modulus of (31.8±6.5) MPa. The particle size of porogen has little effect on the compressive properties and porosities. In addition, the morphology of pores observed by SEM showed good pore interconnectivity within the porous scaffolds. HL-7702 cell viabilities kept at high level during the whole incubation period.