Search

Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. Methods The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. Results RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3′-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. Conclusion In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway.

Based on detection technology of 1 H low-field nuclear magnetic resonance (NMR), this study developed a novel method for assessment and mechanism study of bleeding. This method is sensitive to bleeding water as well as water in cement paste and diluted grout, gives a vivid scenario of microstructure variation and provides important insights into mechanism of bleeding. In this study, influence of parameters such as cement type, water/cement ratio, chemical additives and environmental temperature on bleeding process was investigated. Results show that bleeding property of cements can be rapidly and precisely evaluated by the proposed method. It is found that peaks of T 2 distribution correlate with separated layers of fresh cement paste with bleeding, and the bleeding process generally consists of a significant growth, a relative stable period and a water-sucking stage. Results also demonstrate that retarder significantly increases bleeding, however, bleeding, to a certain extent, can be reduced by the addition of air-entraining agent. Furthermore, bleeding results of the cement paste under different temperatures (15.5 and 22.5 °C) suggest that higher temperature leads to a smaller T 2 value (around 10 ms) and a lower bleeding rate. The high precision of 1 H low-field NMR and linear correlation ( R ⩾ 0.921) between R t ( B ) and bleeding rate both evidenced the superiority and feasibility of the proposed method on study of bleeding.

In the present study, the complete mitochondrial genome of Empoasca sp. was sequenced and assembled. The complete mitogenome of Empoasca sp. was composed of circular DNA molecules, with a total siz...

The target of rapamycin (TOR) plays a central role in eukaryotic cell growth control1. With prevalent hyper-activation of the mTOR pathway in human cancers2, novel strategies to enhance TOR pathway inhibition are highly desirable. We used a yeast-based platform to identify small-molecule enhancers of rapamycin (SMERs) and discovered an inhibitor of the SCFMet30 ubiquitin ligase (SMER3). The large SCF (Skp1-Cullin-F-box) family of ubiquitin ligases performs important functions in diverse cellular processes including transcription, cell-cycle control, and immune response3. Accordingly, there would be great value in developing SCF ligase inhibitors that act by a defined mechanism to specifically inactivate ligase activity. We show here that SMER3 selectively inhibits SCFMet30 in vivo and in vitro, but not the closely related SCFCdc4. Our results demonstrate that there is no fundamental barrier to obtaining specific inhibitors to modulate function of individual SCF complexes, and suggest new strategies for combination therapy with rapamycin.

A multi-objective optimal model is proposed that takes into account minimizing the investment cost of DG and the power loss of distribution network, maximizing the static voltage stability margin, and enhancing the reliability of supply. And this model includes an normalized risk area expressing the uncertainty of DG's output. The immune information processing mechanism of immune system is involved into original particle swarm optimizer. The proposed algorithms have both the properties of the original particle swarm optimization algorithm and the immune mechanism of immune system, can improve the abilities of seeking the global excellent result and evolution speed.