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Background Recent studies show that exosomes are involved in intercellular communication and that abundant circular RNAs (circRNAs) are present within exosomes. However, whether these exosomal circRNAs contribute to tumor invasion and metastasis remains unclear, as do their associated mechanisms. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure the expression levels of circ-IARS in 85 pancreatic ductal adenocarcinoma (PDAC) tissues, plasma exosomes, and Hs 766 T, Hs 766 T-L2 and human microvascular vein endothelial (HUVECs) cells. RhoA, ZO-1 and RhoA-GTP levels were detected by qRT-PCR and western blotting (WB); RhoA activity analysis was also performed. Transwell assays were performed to examine changes in endothelial monolayer permeability, and immunofluorescence and WB were employed to evaluate F-actin expression and focal adhesion. Finally, an animal experiment was performed to detect the contribution of circ-IARS to cancer metastasis. Results circ-IARS expression was up-regulated in pancreatic cancer tissues and in plasma exosomes of patients with metastatic disease. Circ-IARS was found to enter HUVECs through exosomes and promote tumor invasion and metastasis. Circ-IARS expression was positively correlated with liver metastasis, vascular invasion, and tumor-node-metastasis (TNM) stage and negatively correlated with postoperative survival time. Overexpression of circ-IARS significantly down-regulated miR-122 and ZO-1 levels, up-regulated RhoA and RhoA-GTP levels, increased F-actin expression and focal adhesion, enhanced endothelial monolayer permeability, and promoted tumor invasion and metastasis. Conclusions circ-IRAS accesses HUVECs via exosomes derived from pancreatic cancer cells followed by increased endothelial monolayer permeability. Furthermore, this process promotes tumor invasion and metastasis. The results of this study suggest that the presence of circRNAs in exosomes may be important indicator for early diagnosis and prognostic prediction in PDAC.

Background/Aims: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and mechanisms of tumor-generated exosomal miRNAs in progression of PDAC. Methods: miR-222 was identified by miRNA microarray studies in exosomes of PDAC cells, and further analyzed in plasma exosomes of PDAC patients. The regulatory mechanisms of miR-222 were explored by qRT-PCR, WB, dual-luciferase assays and immunofluorescence or confocal analysis. Other biological assays include transwell, xenograft models and so on. Results: miR-222 is significantly high in tumor exosomes or highly invasive PDAC cells. miR-222 could directly regulate p27 to promote cell invasion and proliferation. miR-222 could also activate AKT by inhibiting PPP2R2A expression, thus inducing p27 phosphorylation and cytoplasmic p27 expression to promote cell survival, invasion and metastasis. Expressions of miR-222 and p27 were significantly inversely correlated, and cytoplasmic p27, instead of nuclear p27, was associated with tumor malignancy. miR-222 could be transmitted between PDAC cells via exosome communication, and the exosomal miR-222 communication is functional. Plasma exosomal miR-222 in PDAC patients was high and significantly correlated to tumor size and TNM stage, and was an independent risk factor for PDAC patient survival. Conclusion: Tumor-generated exosomes could promote invasion and proliferation of neighboring tumor cells via miR-222 transmission, the plasma exosomal miR-222 plays important roles and may be a useful prognostic maker in PDAC.

In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models. A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). The pooled Hedges's g with 95% confidence intervals (95% CIs) was adopted to assess the effect size. Random effect model was used due to the heterogeneity between the studies. A total of 20 eligible studies were included in the current systematic review. The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges's g = -2.325 ± 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges's g = -3.488 ± 0.504 with 95% CI: -4.476 ~ -2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges's g = 3.249 ± 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges's g = 2.053 ± 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001). The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges's g = -2.956 ± 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges's g = 3.103 ± 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001). This systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment. Although the COPD models may not truly mimic COPD patients, these pre-clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD. The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair.

This paper presents a linear-nonlinear switching control strategy, called Switching Active Disturbance Rejection Control (SADRC), to enhance the disturbance rejection capability of the speed controller in a servo system. SADRC combines the advantages of Linear Active Disturbance Rejection Control (LADRC) and Nonlinear Active Disturbance Rejection Control (NLADRC), and introduces a parameter to switch between nonlinear and linear control, thereby improving the robustness of the servo system. Firstly, the mathematical model of the motor is analyzed as the starting point of the paper. Then, the basic principles of Active Disturbance Rejection Control (ADRC) are analyzed, and improvements are made to address its limitations, resulting in the design of SADRC. The parameters introduced in SADRC are analyzed to determine their appropriate ranges. Finally, the performance of SADRC is validated by comparing the rotational effects of Permanent Magnet Synchronous Motor (PMSM).

PurposeWith the development of technology, the application scenarios of mobile robots are becoming more and more extensive, accompanied by a variety of application scenarios suitable and safe path planning algorithms are indispensable for mobile robots.Design/methodology/approachThe purpose of this paper to improve the safety performance of your bot during the execution of tasks. The methods are synthesized in three main areas: setting appropriate safety distances based on the actual radius of the robot, turn penalty reduces the number of turns by applying an additional penalty to the number of turns in a heuristic function and path smoothing is used to improve path reliability by reducing the number of right-angle turns.FindingsA suitable safety distance greatly improves the safety of mobile robots and facilitates their development. Optimization of turns in the path of mobile robots improves the travel efficiency of robots. Enhancing the safety of mobile robots has become a research hotspot for path-planning algorithms.Originality/valueThis paper proposes a path planning scheme for mobile robots with safe distances, which provides readers with a comprehensive and systematic progress of path planning research. It helps readers to get inspiration from enhancing the safety of mobile robots.

Studies on 3D-printed porous bone scaffolds mostly focus on materials or structural parameters, while the repair of large femoral defects needs to select appropriate structural parameters according to the needs of different parts. In this paper, a kind of stiffness gradient scaffold design idea is proposed. Different structures are selected according to the different functions of different parts of the scaffold. At the same time, an integrated fixation device is designed to fix the scaffold. Finite element method was used to analyze the stress and strain of homogeneous scaffolds and the stiffness gradient scaffolds, and the relative displacement and stress between stiffness gradient scaffolds and bone in the case of integrated fixation and steel plate fixation. The results showed that the stress distribution of the stiffness gradient scaffolds was more uniform, and the strain of host bone tissue was changed greatly, which was beneficial to the growth of bone tissue. The integrated fixation method is more stable, less stress and evenly distributed. Therefore, the integrated fixation device combined with the design of stiffness gradient can repair the large femoral bone defect well.

Background The Pringle maneuver (PM) interrupts the blood flow through the hepatic artery and portal vein to help control bleeding. This study analyzes the effects of the intermittent Pringle maneuver (IPM) on the surgical process and postoperative liver injury. Methods This study retrospectively evaluated 182 hepatocellular carcinoma patients who underwent hepatectomy. In the IPM group, hepatic blood flow was intermittently interrupted via clamping, with cycles of 10 minutes of inflow occlusion followed by 5 minutes of reperfusion that were repeated until the end of the surgery. In the non-IPM group, liver resection was performed without hepatic vascular blockage. Results For postoperative complications, the incidence rates of ascites and pleural effusion in the IPM group were significantly lower than those in the non-IPM group. The postoperative hospitalization time in the IPM group was significantly lower than that in the non-IPM group ( p =0.0008). On the first day after the operation, the platelet count was significantly lower ( p =0.0381) but the prothrombin time (PT) ( p =0.0195) and activated partial thromboplastin time (APTT) ( p =0.0071) were significantly higher in the non-IPM group than those in the IPM group. At discharge, only albumin was significantly higher in the non-IPM group than that in the IPM group ( p =0.0303). Regression analysis showed that a prolonged interruption time was related to increased ALT and AST levels on the first day after surgery, but not on the seventh day or at discharge. Conclusion The IPM does not cause additional liver damage during hepatectomy, and use of the IPM results in shorter hospital stays compared to surgery without using the IPM. The results of this study require further confirmation because of the retrospective design.

Vitamin D insufficiency has been increasingly recognized in the general population worldwide and has been associated with several lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and respiratory tract infections. Fibroblasts play a critical role in tissue repair and remodeling, which is a key feature of COPD and asthma. Fibroblasts modulate tissue repair by producing and modifying extracellular matrix components and by releasing mediators that act as autocrine or paracrine modulators of tissue remodeling. The current study was designed to investigate if vitamin D alters fibroblast release of key autocrine/paracrine repair factors. First, we demonstrated that human fetal lung (HFL)-1 cells express the vitamin D receptor (VDR) and that vitamin D, 25-hydroxyvitamin D [25(OH)D], or 1,25-dihydroxyvitamin D [1,25(OH)2D] induce VDR nuclear translocation and increase VDR-DNA binding activity. We next demonstrated that vitamin D, 25(OH)D, and 1,25(OH)2D significantly reduced prostaglandin (PG)E2 production by human lung fibroblasts (HFL-1) but had no effect on transforming growth factor β1, vascular endothelial growth factor, or fibronectin production. Vitamin D, 25(OH)D, and 1,25(OH)2D significantly inhibited IL-1β-induced microsomal PGE synthase (mPGES)-1 expression; in contrast, all three forms of vitamin D stimulated 15-hydroxy PG dehydrogenase, an enzyme that degrades PGE2. Cyclooxygenase-1 and -2 and the other two PGE2 synthases (mPGES-2 and cytosolic PGE synthase) were not altered by vitamin D, 25(OH)D, or 1,25(OH)2D. Finally, the effect of PGE2 inhibition by 25(OH)D was observed in adult lung fibroblasts. These findings suggest that vitamin D can regulate PGE2 synthesis and degradation and by this mechanism can modulate fibroblast-mediated tissue repair function.

Fibroblasts are believed to be the major cells responsible for the production and maintenance of extracellular matrix. Alterations in fibroblast functional capacity, therefore, could play a role in the pathogenesis of pulmonary emphysema, which is characterized by inadequate maintenance of tissue structure. To evaluate the hypothesis that deficient fibroblast repair characterizes cells obtained from individuals with chronic obstructive pulmonary disease (COPD) compared with control subjects. Fibroblasts were cultured from lung tissue obtained from individuals undergoing thoracotomy and were characterized in vitro. Fibroblasts from individuals with COPD, defined by reduced FEV(1), manifested reduced chemotaxis toward fibronectin and reduced contraction of three-dimensional collagen gels, two bioassays associated with fibroblast repair function. At least two mechanisms appear to account for these differences. Prostaglandin E (PGE), a known inhibitor of fibroblast repair functions, was produced in increased amount by fibroblasts from subjects with COPD, which also expressed increased amounts of the receptors EP2 and EP4, both of which signal through cyclic AMP. Incubation of fibroblasts with indomethacin or with the PKA inhibitor KT-5720 partially restored COPD subject fibroblast function. In addition, fibroblasts from subjects with COPD produced more transforming growth factor (TGF)-beta1, but manifested reduced response to TGF-beta1. The functional alterations in fibroblasts correlated with both lung function assessed by FEV(1) and, for the data available, with severity of emphysema assessed by Dl(CO). Fibroblasts from individuals with COPD have reduced capability to sustain tissue repair, which suggests that this may be one mechanism that contributes to the development of emphysema.

Oncostatin M (OSM), an inflammatory cytokine of the interleukin-6 (IL-6) superfamily, plays a key role in various biological processes such as modulation of extracellular matrix (ECM), cell proliferation, cell survival, and induction of inflammation. It has been reported that OSM was increased in asthma and pulmonary fibrosis, and thus OSM may play a role in airway remodeling and the development of lung parenchymal fibrosis. Recruitment of lung fibroblasts to the sites of airway injury and subsequent differentiation into myofibroblasts is believed to contribute to excess ECM deposition. In the current study, we assessed the ability of OSM to modulate fibroblast collagen gel contraction, migration toward fibronectin, and expression of α-smooth muscle actin (α-SMA). We demonstrated that OSM augments gel contraction, chemotaxis, and α-SMA expression. OSM-augmented fibroblast chemotaxis was mediated by the signal transducer and activator of transcription (STAT3) and p38 mitogen-activated protein kinase, while augmentation on gel contraction and α-SMA expression was mediated by STAT3. Neither transforming growth factor-β1 nor PGE2 was involved in mediating OSM effect on the cells. The Th2 cytokines IL-4 and IL-13, which also are believed to play an important role in promoting lung fibrosis and airway remodeling, act through STAT3, and we demonstrated the potential for additive effects of OSM with IL-4 and IL-13. The present study supports the concept that OSM may contribute to tissue remodeling, which may be additive with IL-4 or IL-13. Blockade of OSM or OSM-mediated STAT3 signaling could be a therapeutic target to regulate lung fibrotic mechanisms.