LPAR2-mediated action promotes human renal cell carcinoma via MAPK/NF-κB signaling to regulate cytokine network.

PURPOSE: Lysophosphatidic acid (LPA) exerts various physiological and pathological effects by activating its distinct G-protein-coupled LPA receptors. We demonstrated that LPA can increase the migration and proliferation of renal carcinoma cells. Meanwhile, LPAR1 and LPAR2 were preferentially expressed in renal cancer (RC) cell lines. So, the study aimed to determine the LPA receptor subtypes involved in LPA-induced actions and whether they could be used as a precision therapeutic target for renal cancer. METHODS: Biological approaches combined with big data analysis were used to demonstrate the role of LPAR2 in the progression of renal cancer. RESULTS: We found that the proliferation, clone formation, and migration in response to LPA were enhanced in LPAR2-overexpressing renal cancer cells, whereas, the actions were suppressed by LPAR2 antagonist in the cells. LPAR2 has also shown clinical diagnostic and prognostic value in renal carcinoma based on bioinformatics analysis and clinical tissue microarray analysis. In vivo study shown that tumor growth and metastasis were significantly increased in the LPAR2-overexpressing cells-derived solid tumors. LPA stimulated MAPK and NF-κB activation, and LPA-induced actions were inhibited by MAPKs and NF-κB inhibitors, respectively. Subsequently, the transcriptomic results revealed that LPAR2 strongly affected the cytokines production, and the increased IL6, CXCL8, and TNF were confirmed again using Kit assay. CONCLUSIONS: We have identified that LPAR2 is critical for LPA-promoted renal cancer progression, and the actions mainly dependent the MAPK and NF-κB activation mechanism. Then, the expression of inflammatory factors activated by NF-κB is also suspected to be involved in LPAR2-mediated carcinogenesis. Thus, LPAR2 may be a promising therapeutic target for renal cancer.

Corrosion behavior of X80 pipeline steel local defect pits under static liquid film.

In this work, the corrosion electrochemical information under different thicknesses of liquid film was tested. The local corrosion development process of X80 steel under different thicknesses of liquid film was studied by combining the detection and analysis of scale and the matrix corrosion morphology. The corrosion was studied by EIS. The composition and microstructures of corrosion scale at different locations were detected by EDS and SEM, and the metal matrix was detected by 3D topography technology to analyze the local corrosion. The results show that a liquid film with a thickness greater than or equal to 1 mm has no effect on the mechanism of the corrosion process, but has a control effect on the corrosion rate and the time of each stage in corrosion. The corrosion process can be divided into two stages: in the early stage, the concentration of ions inside and outside ADP is the same, so the corrosion is uniform; in the later stage, due to the influence of CO2 dissolution and mass transfer distance, the cathodic reaction is mainly outside ADP and the anodic reaction is mainly inside ADP. In addition, corrosion acidification occurs in ADP, which enhances the corrosion process in ADP.

Microstructure, mechanical properties and springback behaviour of Ti­6Al­4V alloy connection rod for spinal fixation device.

The effect of annealing condition on microstructure, mechanical properties and springback behaviour was examined in the connection rod of Ti-6Al-4V alloy for spinal fixation devices. Compared with the deformed microstructure in the sample before annealing, relatively few equiaxed grains were present after annealing at 1003 K after 1.8 ks, and a considerable amount appeared at 7.2 ks. When annealing time was extended to 36 ks, the recrystallised grains further grew. Vickers hardness, tensile strength and bending strength decreased with increasing annealing time, whereas the elastic and bending moduli showed no significant change with annealing time of up to 7.2 ks and then slightly decreased at 36 ks. The springback ratio was closely associated with strength and modulus and applied bending deflection. The springback ratio reached the highest and lowest values in the sample before and after annealing for 7.2 ks, respectively. A good combination of strength, modulus and springback ratio was obtained in the sample after annealing for 7.2 ks.