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Aim: This study aimed to evaluate the miR-223-5p expression in patients with spinal cord injury (SCI) and to determine its role in the pathogenesis of SCI. Methods: The serum miR-223-5p levels were analyzed using quantitative real-time polymerase chain reaction. The diagnostic accuracy of miR-223-5p was evaluated using the receiving operating characteristic curves. LPS-induced PC12 cells were established as an in vitro inflammatory cell model. Cell apoptosis, inflammation and oxidative stress were examined. The SCI rat model was constructed to evaluate the effects of miR-223-5p on inflammatory response and motor function in rats. Results: MiR-223-5p expression was upregulated in SCI patients. MiR-223-5p expression in the complete SCI group was significantly higher than that in incomplete SCI group. ROC analysis showed that miR-223-5p can distinguish SCI patients from healthy volunteers. In vitro experiments demonstrated that LPS upregulated apoptosis and inflammation in PC12 cells. Treatment with miR-223-5p inhibitor alleviated the changes in LPS-induced PC12 cells. Inhibition of miR-223-5p can alleviate the activation of inflammatory response and the effects of SCI on the motor function in rats. Conclusions: MiR-223-5p is a potential diagnostic marker for SCI, and it can promote the SCI progression by regulating nerve cell survival, inflammation, and oxidative stress. [ABSTRACT FROM AUTHOR]

The proton-exchange membrane fuel cell is a promising power source for automobile industry because of its zero pollution. However, its stack structure always faces increased contact resistance caused by assembly errors, leading to substantial energy loss during the working period. To enhance its output performance, the influence of assembly errors on contact resistance is studied for proton-exchange membrane fuel cell. The mechanical simulation model of fuel cell assembly process is established to provide contact resistance distribution with different assembly errors. An improved global sensitivity analysis method is proposed to evaluate the influence coefficient of each assembly error term on contact resistance based on a series of randomized simulation data. The case study of a single-layer fuel cell demonstrates the proposed method achieves higher efficiency than traditional sensitivity analysis methods, and finds out key assembly errors in regard to reducing contact resistance. [ABSTRACT FROM AUTHOR]

Abstract Background Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease. Methods We induced OA via intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents. Results OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase. Conclusions Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.

The present study aimed to investigate the effects of the long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on proliferation, apoptosis and the inflammatory response of osteoarthritic chondrocytes (OACs) and its associated mechanism of action. Primary chondrocytes were isolated from cartilage tissues of osteoarthritis (OA) patients for subculture. GAS5 was silenced in OACs by liposome transfection. The effects of GAS5 silencing on proliferation, apoptosis, stromal metabolism and inflammatory response of OACs were analyzed. The association of GAS5 with its target microRNA-34a (miR-34a) and the downstream target gene Bcl-2 was verified by luciferase reporter assays. The results indicated that GAS5 silencing promoted the proliferation, inhibited cell apoptosis and caused G1 arrest of OACs compared with the control group (P<0.05). The expression levels of TNF-α and IL-6 in the supernatant of OACs in the si-GAS5 group were significantly lower than those of the control group (P<0.05). The results of the double luciferase reporter assays indicated that overexpression of GAS5 downregulated miR-34a and upregulated Bcl-2 levels (P<0.05) compared with the expression levels of these markers in the control group. In contrast to GAS5 overexpression, knockdown of this RNA caused a significant upregulation of miR-34a levels and a significant downregulation in the levels of Bcl-2 (P<0.05). Moreover, GAS5 overexpression could counteract the inhibition of apoptosis by overexpression of miR-34a (P<0.05). The data indicated that GAS5 participated in the development of OA by regulating the biological behavior of chondrocytes via the miR-34a/Bcl-2 axis. [ABSTRACT FROM AUTHOR]

For fiber-reinforced composites, the anisotropy and the tension-compression asymmetry have very important influence on fatigue performance. The quasi-static and fatigue mechanical behavior of plain weave laminates of carbon/polymer composites were experimentally investigated in this paper. The quasi-static and stress-controlled fatigue tests were carried out on the servo-hydraulic material testing machine. Fracture failure surfaces were observed in micro-mechanism with scanning electron microscopy. A phenomenological and nonlinear constant life diagram (CLD) model was developed based on quasi-static strength andS–Ncurve data-sets of different stress ratios. The relationship between six parameters of the proposed model and the failure cycles was studied. The fatigue experimental results showed that the fatigue failure type changed from tensile mode to compressive mode at nearby stress ratioR = −0.2. A satisfactory agreement between the predicted value of cycle life and experimental data was observed. The results indicated that the fatigue performance was adequately described by the BasquinS–Nformulation and proposed CLD. [ABSTRACT FROM PUBLISHER]

Objective: To explore a method of loading exosomes onto absorbable stents., Methods: By building a stent-(3-aminopropyl) triethoxysilane-1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) 5000]-exosomes connection, the exosomes were loaded onto absorbable stents to obtained the exosome-eluting absorbable stents. The surface conditions of the stents and absorption of exosomes were observed by scanning electron microscope and identified through the time-of-flight mass spectrometry; the roughness of the stents' surfaces was observed by atomic force microscope; the appearances and sizes of the stents were observed by stereomicroscope; and the radial force was tested by tensile test machine. The absorbable stents were used as control., Results: The scanning electron microscope observation showed that the exosome-eluting absorbable stents had some small irregular cracks on the surface where many exosomes could be seen. The atomic force microscopy observation showed that within the range of 5 μm 2 , the surface roughness of the absorbable stents was ±20 nm, while the surface roughness of the exosome-eluting absorbable stents was ±70 nm. In the results of time-of-flight mass spectrometry, both the exosome-eluting absorbable stents and exosomes had a peak at the mass charge ratio of 81 (m/z 81), while the absorbable stents did not have this peak. The peak of exosome-eluting absorbable stents at m/z 73 showed a significant decrease compared to the absorbable stents. The stereomicroscope observation showed that the sizes of exosome-eluting absorbable stents met standards and the surfaces had no cracks, burrs, or depressions. The radial force results of the exosome-eluting absorbable stents met the strength standards of the original absorbable stent., Conclusion: By applying the chemical connection method, the exosomes successfully loaded onto the absorbable stents. And the sizes and radial forces of this exosome-eluting absorbable stents meet the standards of the original absorbable stents.

Objective: To investigate the expression of long-chain noncoding RNA GAS5 in osteoarthritis (OA) and the effect of silencing GAS5 on autophagy of osteoarthritis chondrocytes (OACs)., Methods: OA rat models were constructed by cutting the anterior cruciate ligament, and the expressions of GAS5 in rat cartilage tissues at 4 weeks (early OA) and 12 weeks (late OA) after modeling were detected. The rat chondrocytes were isolated, cultured and transfected with si-GAS5 to silencing GAS5. Then, the changes of apoptosis and autophagy levels of OA chondrocytes were detected by transfection of GFP-LC3 and flow cytometry. Bioinformatic tools were used to analyze the miRNA binding to GAS5 and the downstream target genes, then luciferase reporter assay and GDC-0349 (inhibitor of mTOR) were used to verify their relationships., Results: The expression of GAS5 in cartilage tissue of OA rats was higher than control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OACs was increased and the apoptosis rate was decreased. GAS5 was able to bind to miR-144 and regulate the expressin of mTOR. mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on autophagy but could not reverse its effect on apoptosis., Conclusion: GAS5 expresses highly in OA cartilage tissues and increases with the progression of OA. GAS5 inhibits autophagy and promotes the apoptosis of OACs, and the inhibition of autophagy may be related to its regulation of mTOR.