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ObjectiveRAD51 is a DNA repair protein, which participates in the resistance of tumor cells to radiotherapy/chemotherapy and reduces the therapeutic effect. Based on the research status of RAD51 at home and abroad and the analysis of online databases, the purpose of this study was to explore the relationship between RAD51 expression and clinical patient survival and prognosis. It is expected to provide a new theoretical basis for the clinical treatment of lung cancer patients, help identify new molecular markers, and provide new targets for the biological therapy of lung cancer patients.Methodsthe RNA Seq data of NSCLC in TCGA database were downloaded, and the expression of RAD51 gene in NSCLC and normal tissues were analyzed by R studio software. Clinical correlation analysis revealed its correlation with the clinicopathological characteristics of non-small cell lung cancer. Survival analysis was used to evaluate the relationship between the expression level and the prognosis of patients. CIBERSORT and TIMER were used to evaluate the correlation between the expression level of CIBERSORT and immune cells in the tumor microenvironment. The protein expression level of RAD51 in non-small cell lung cancer was evaluated by HPA.ResultsRAD51 was highly expressed in lung cancer (p0.05). The HPA database indicated that RAD51 protein was positive in non-small cell lung cancer.ConclusionRAD51 is highly expressed in non-small cell lung cancer and is associated with poor prognosis. RAD51 can be used as a biomarker related to the prognosis of non-small cell lung cancer and is expected to become a target for the diagnosis and treatment of non-small cell lung cancer.

Liver is an important organ for regulating glucose and lipid metabolism. Recent studies have shown that bone morphogenetic proteins (BMPs) may play important roles in regulating glucose and lipid metabolism. In our previous studies, we demonstrated that BMP4 significantly inhibits hepatic steatosis and lowers serum triglycerides, playing a protective role against the progression of non-alcoholic fatty liver disease (NAFLD). However, the direct impact of BMP4 on hepatic glucose metabolism is poorly understood. Here, we investigated the regulatory roles of BMP4 in hepatic glucose metabolism. Through a comprehensive analysis of the 14 types of BMPs, we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation, reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism. Mechanistically, we demonstrated that BMP4 reduced the hepatic glucose levels through the activation of mTORC2 signaling pathway in vitro and in vivo. Collectively, our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism. This knowledge should aid us to understand the molecular pathogenesis of NAFLD, and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.

This paper adopts the fractional cointegrated vector autoregressive (FCVAR) model to examine high-frequency price discovery of bitcoin spot and futures prices from December 18, 2017 to July 31, 2020 We find that bitcoin spot and futures prices exhibit long memory properties and they are fractionally cointegrated The result shows that the bitcoin futures market dominates the price discovery process Interestingly, during the Covid-19 pandemic, the bitcoin price discovery leadership has switched to the spot market Moreover, we find that the bitcoin futures market follows a long-run contango The nonfractional CVAR model overestimates the price discovery of the futures market © 2021 Wiley Periodicals LLC

It has been reported that chemokine CX3 CL1 can regulate various tumours by binding to its unique receptor CX3 CR1. However, the effect of CX3 CL1-CX3 CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3 CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3 CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3 CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3 CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3 CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3 CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3 CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.

BACKGROUND: The aim of this study is to evaluate the optic nerve sheath diameter (ONSD) in eyes with dysthyroid optic neuropathy (DON) and its relationship with clinical characteristics and disease severity. METHODS: Patients diagnosed as thyroid-associated ophthalmopathy (TAO), with or without DON, and healthy participants were recruited. Vertical and horizontal sectional images of the optic nerve were collected by B-scan ultrasonography. ONSDs at 3 mm and 6 mm behind the eyeball were measured independently by two researchers. Multivariate regression analysis was performed to evaluate the association of ONSD with demographic and ocular parameters in TAO patients. Areas under the receiver operating characteristic curves (AUROCs) were applied to evaluate the diagnostic accuracy of ONSD for DON. RESULTS: A total of 47 healthy eyes, 36 TAO eyes without DON, and 33 eyes with DON were studied. ONSDs at 3 mm and 6 mm of DON eyes were significantly higher than those in non-DON and healthy eyes (all P 0.05). DON occurrence showed a positive association with both ONSDs at 3 mm (β = 0.49, 95% CI: 0.14–0.83, P = 0.007) and 6 mm (β = 0.58, 95% CI: 0.20–0.96, P = 0.003). ONSDs at 3 mm and 6 mm showed a desirable diagnostic capacity to distinguish DON from non-DON eyes (AUROC was 0.77 and 0.75, respectively). CONCLUSIONS: An increase in ONSD is evident in DON eyes independent of clinical activity. Ultrasound-based ONSD has sufficient ability to distinguish DON from non-DON eyes.

Gut microbiota can promote tumor development by producing toxic metabolites and inhibiting the function of immune cells. Previous studies have demonstrated that gut microbiota can reach the liver through the circulation and promote the occurrence of liver cancer. Ciprofloxacin, an effective broad-spectrum antimicrobial agent, can promote cell apoptosis and regulate the function of immune cells. As an important part of the tumor microenvironment, macrophages play an important role in tumor regulation. The present study demonstrated that the treatment of macrophages with ciprofloxacin was able to promote the production of interleukin-1β, tumor necrosis factor-α and the polarization of CD86+CD206− macrophages, while inhibiting the polarization of CD86−CD206+ macrophages. This transformation may help macrophages promote tumor cell apoptosis, inhibit tumor cell proliferation, reduce metastasis and downregulate the phosphoinositide 3-kinase/AKT signaling pathway in liver cancer cell lines. In vivo experiments demonstrated that macrophages treated with ciprofloxacin inhibited the growth of subcutaneous implanted tumors in nude mice. In conclusion, the findings of the present study indicated that ciprofloxacin may inhibit liver cancer by upregulating the expression of CD86+CD206− macrophages. This study further revealed the biological mechanism underlying the potential value of ciprofloxacin in antitumor therapy and provided new targets for the treatment of liver cancer.

Inflammation is implicated in the pathogenesis of calcific aortic valve disease (CAVD) which is a major contributor to cardiovascular mortality and lacks non-surgical treatment. The progranulin (PGRN) is an important immunomodulatory factor in a variety of inflammatory diseases, including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease and pneumonia. However, its role in calcification of aortic valve remains unknown. We firstly found that PGRN was increased in calcified human aortic valve (AV) tissues. Interestingly, in addition to full-length PGRN (68KD), a much stronger band of approximately 45 KD was also significantly increased. The band of 45 KD (45-GRN), was present in wild type (WT) mouse MEFs and AV but absent in grn-/-MEFs, indicating that it was a specific degradation product derived from PGRN. 45-GRN was upregulated whereas PGRN was reduced in human valve interstitial cells (hVICs) under calcifying conditions which is induced by osteogenic medium (OM). In primary porcine VICs (pVICs), PGRN downregulated TNF-α and α-SMA which was accompanied by downregulation of RUNX2, OPN, OCN, alkaline phosphatase activity and calcium deposition, effects pointing to reduced inflammation, myofibroblastic and osteoblastic transition under calcifying conditions. We overexpressed a mimic of 45-GRN which contains p-G-F-B-A-C in pVICs. However, 45-GRN overexpression promoted OM-induced calcification through activating the Smad1/5/8, NF-κB and AKT signaling pathways. Inhibition of the three signaling pathways suppressed 45-GRN's effect on VICs phenotype transition. 45-GRN promoted TNF-α and expressed converse pathogenic signatures with PGRN during TNF-α stimulation. Collectively, this study provides new insight into the pathogenesis of CAVD, indicating that PGRN is a stratagem in mitigating valve fibrosis/osteoblastic differentiation, and also presenting 45-GRN as a potential target for the treatment of CAVD.

Software Defined Network (SDN) currently is widely used in the implementation of new network technologies owing to its distinctive advantages. In changeable SDN environments, the update performance of SDN switches has significant importance for the overall network performance because packet processing could be interrupted by ruleset updating in SDN switches. In order to guarantee high update performance, we propose a new classification algorithm, SplitTrie, based on trie structures and trie splitting. SplitTrie splits rulesets according to the field type vectors of rules. The splitting can improve the update performance because it reduces the trie structure sizes. Experimental results demonstrated that SplitTrie could achieve 20 times of update speed in the complex rulesets comparing the method without trie splitting.

With the development of the construction industry, traditional architectural forms are gradually being replaced by various new architectural forms, prefabricated concrete structure building is one of them. Prefabricated concrete structure buildings not only improve the disadvantages of traditional buildings such as slow construction speed and low efficiency, but also effectively guarantee the quality and performance of the building. BIM technology is building information modeling technology, which has a very important application in the design of prefabricated concrete structures. In this paper, a complex concrete structure is designed according to BIM technology and computer simulation.

Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD in vivo. Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD.

In recent years, the construction of urban highway through slope excavation becomes more and more widespread. However, the surcharge loading induced by dense buildings is often neglected. For a better understanding of the deformation characteristics and associated failure mechanism of such slopes, a series of model tests have been carried out using distributed strain sensing (DSS) technology. The coupling between DSS cables and surrounding soil is the most critical factor affecting the validity of slope deformation measurements. Therefore, a cable pull-out test is conducted to investigate the coupling effect. It is founded that 200 KPa is the critical confining pressure (CP). Once the CP exceeds this value, the synchronous deformation of DSS cable and soil can be guaranteed, which can be regarded as criterion to guide laboratory test and in-situ monitoring. After the deformation compatibility is ensured, a surcharge loading model test is designed and DSS cables are horizontally and vertically installed. The strain variation exhibited on the DSS cables reveal that the crest and toe areas of the slope show a thrust load-induced and retrogressive failure patterns respectively. It indicates that a shadow sliding surface can occur during slope excavation, which is rarely witnessed in previous studies. The safety factor can be calculated by the slice method. It is founded that the horizontal maximum strain can reflect the stability of the model slope and an exponential function has been established. The results are likely to provide a good indication of the stability of such slopes.

Fountain is an important facility in modern landscape art. Ordinary fountains are regulated by water valves, which makes the water column of the fountain very high, so the height of the fountain cannot be changed flexibly, the fountain is the product of the combination of the most popular garden architecture and appreciation in recent years. In this paper, intelligent control system based on feature recognition is designed. According to the system, fountain forms and features can be recognized automatically. At the same time, the system can also be integrated with computer animation, which makes the melody, emotion, rhythm and waterscape art to realize harmonious and unified.

It has been reported that chemokine CX3CL1 can regulate various tumours by binding to its unique receptor CX3CR1. However, the effect of CX3CL1‐CX3CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3CL1 up‐regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c‐Src and c‐Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.

Plane wave expansion (PWE) method is extended to calculate the band structures of a proposed piezoelectric phononic crystal (PC) nanobeam by applying surface elasticity and Timoshenko beam theories. The calculation method is derived and formulized in detail. Further, electrical voltage and external axial force are picked to study the effects of electro-mechanical coupling fields on band gaps, residual surface stress and material intrinsic length are chosen to research the influences of surface effects on band gaps, and ratio between lengths of PZT-4 and epoxy in a unit cell and height-width ratio are picked to investigate the effects of geometric parameters on band gaps. In addition, all the results are compared to those in Euler nanobeam with same parameters. All the results and further analysis demonstrate that the influence rules will play an active role in design process and active control of nano electro-mechanical system based on piezoelectric PC nanobeam.

Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD in vivo. Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD.

Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non‐alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long non‐coding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up‐regulated in oleic acid‐induced steatosis and during the development of high‐fat diet (HFD)‐induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up‐regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up‐regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19‐induced lipid accumulation in hepatocytes. Furthermore, H19‐induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF‐04691502. Accordingly, H19 overexpression in hepatocytes up‐regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up‐regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these findings strongly suggest that H19 may play an important role in regulating hepatic lipid metabolism and may serve as a potential therapeutic target for NAFLD.

Concrete structures are easy to produce cracks which seriously affect the safety of the structures. Rayleigh based distributed optical fiber sensing technique has been used to measure the strain field evolution associated with crack initiation and growth in concrete structures. A reinforced concrete beam has been tested under four-point loading test with optical fibers both pasted on the surface and embedded as the distributed sensors. Experimental results indicate that cracks can be detected at sharp peaks of the measured strain distributions, which can be utilized to effectively capture the number of cracks and locate multiple cracks. The abilities of using optical frequency domain reflectometry (OFDR) technology to detect hairline cracks and distinguish neighboring cracks are also discussed. Single crack opening displacement is determined through fitting process which taken the influence of intermediate layers into consideration, the widening and propagation of cracks in the overall concrete beam were detected.