The palmitoylation of AEG-1 dynamically modulates the progression of hepatocellular carcinoma.

Rationale: Protein palmitoylation is tightly related to tumorigenesis or tumor progression as many oncogenes or tumor suppressors are palmitoylated. AEG-1, an oncogene, is commonly elevated in a variety of human malignancies, including hepatocellular carcinoma (HCC). Although AEG-1 was suggested to be potentially modified by protein palmitoylation, the regulatory roles of AEG-1 palmitoylation in tumor progression of HCC has not been explored. Methods: Techniques as Acyl-RAC assay and point mutation were used to confirm that AEG-1 is indeed palmitoylated. Moreover, biochemical experiments and immunofluorescent microscopy were applied to examine the cellular functions of AEG-1 palmitoylation in several cell lines. Remarkably, genetically modified knock-in (AEG-1-C75A) and knockout (Zdhhc6-KO) mice were established and subjected to the treatment of DEN to induce the HCC mice model, through which the roles of AEG-1 palmitoylation in HCC is directly addressed. Last, HCQ, a chemical compound, was introduced to prove in principal that elevating the level of AEG-1 palmitoylation might benefit the treatment of HCC in xenograft mouse model. Results: We showed that AEG-1 undergoes palmitoylation on a conserved cysteine residue, Cys-75. Blocking AEG-1 palmitoylation exacerbates the progression of DEN-induced HCC in vivo. Moreover, it was demonstrated that AEG-1 palmitoylation is dynamically regulated by zDHHC6 and PPT1/2. Accordingly, suppressing the level of AEG-1 palmitoylation by the deletion of Zdhhc6 reproduces the enhanced tumor-progression phenotype in DEN-induced HCC mouse model. Mechanistically, we showed that AEG-1 palmitoylation adversely regulates its protein stability and weakens AEG-1 and staphylococcal nuclease and tudor domain containing 1 (SND1) interaction, which might contribute to the alterations of the RISC activity and the expression of tumor suppressors. For intervention, HCQ, an inhibitor of PPT1, was applied to augment the level of AEG-1 palmitoylation, which retards the tumor growth of HCC in xenograft model. Conclusion: Our study suggests an unknown mechanism that AEG-1 palmitoylation dynamically manipulates HCC progression and pinpoints that raising AEG-1 palmitoylation might confer beneficial effect on the treatment of HCC.

Feasibility Study on the Steel-Plastic Geogrid Instead of Wire Mesh for Bolt Mesh Supporting.

Wire mesh is a common material for bolt mesh supporting structures, but its application in engineering has revealed many defects. At the same time, with the development of new materials for civil engineering, the new material mesh performance and cost show outstanding advantages over wire mesh. In this paper, the feasibility of replacing wire mesh with steel-plastic geogrid as an alternative material is carefully studied through indoor tests and field applications. The following conclusions were drawn from a comparative analysis with wire mesh, mainly in terms of mechanical properties, engineering characteristics, and construction techniques: (1) in terms of mesh wire strength, wire mesh is slightly better than steel-plastic geogrid, but in the case of similar tensile strength, the amount of steel used per unit length of steel geogrid bars is only 36.75% of that of steel-plastic geogrid, while the tensile strength of the high-strength steel wire attached to the steel-plastic geogrid belt is about 3.3 times that of steel bars; (2) in terms of junction peel strength, both values are similar, with the injection-moulded junction being 1154.56-1224.38 N and the welded junction of 4 mm mesh being 988.35 N; (3) in terms of the strength of the mesh, steel-plastic geogrid is better than wire mesh, and with the same mesh wire strength, the bearing capacity of steel-plastic geogrid is increased by about 63.17% and the contribution of the mesh wire bearing capacity is increased by 83.66%, with the damage mainly being in the form of wire breakage in the ribbon causing ribbon failure, leading to further damage to the mesh; (4) in terms of the engineering application of steel-plastic geogrid compared to wire mesh, the utilization rate of mesh increases by about 24.99%, the construction efficiency increases by about 14.10%, and the economic benefit increases by about 45.31%. In practical application, the steel-plastic geogrid has good adhesion with surrounding rock and strong corrosion resistance. According to the above research analysis, the steel-plastic geogrid is feasible to replace the wire mesh for bolt mesh supporting.

Experimental Study on Carbonation Durability of Kaolin Strengthened with Slag Portland Cement.

Slag Portland cement is an environmentally friendly and energy-saving product, which is widely used in cement-reinforced soil. This study used slag Portland cement-reinforced soil as the research object and P.O 42.5 + kaolin (POK) as the reference group. The carbonation depth and strength of P.S.A 42.5 + kaolin (PSK) at different curing times were analyzed using carbonation depth, uniaxial ground pressure strength, scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD). The test results show the following: (1) The active substances in PSK samples can react with calcium hydroxide produced during cement hydration and can reduce the content of OH-. The PSK samples react with OH- and CO2 in the carbonation environment. Both processes considerably reduce the content of OH-. (2) Due to the decrease in OH- content, the carbonation durability of slag Portland cement-reinforced soil is significantly less than that of ordinary Portland cement. (3) The carbonation of slag Portland cement-reinforced soil improves its strength. (4) The results of SEM + EDS and XRD confirm the carbonation depth and strength of the POK and PSK samples. The results show that PSK has important applications in subgrade or building grouting materials and in cement-soil mixing piles (walls).

Experimental Study on Tensile Mechanical Properties and Reinforcement Ratio of Steel-Plastic Compound Geogrid-Reinforced Belt.

The steel-plastic compound geogrid has been widely used as a new reinforcement material in geotechnical engineering and other fields. Therefore, it is essential to fully understand the mechanical properties of steel-plastic compound geogrid-reinforced belts to utilize steel-plastic compound geogrids efficiently. In this study, tensile mechanical tests of steel wire, polyethylene geogrid belt, and steel-plastic compound geogrid-reinforced belt were conducted with respect to the tensile mechanical properties of steel-plastic compound geogrid-reinforced belts. In addition, the minimum reinforcement and optimal reinforcement ratios of steel-plastic compound geogrid-reinforced belts were summarized. The results showed that the steel-plastic compound geogrid-reinforced belts possessed an incongruent force of the internal steel wire during the tensile process. The tensile stress-strain curve of the steel-plastic compound geogrid-reinforced belt can be divided into the composite adjustment, steel wire breaking, and residual deformation stages. The tensile strength of the steel-plastic compound geogrid-reinforced belt is proportional to the diameter and number of steel wires in the reinforced belt. The minimum and optimum reinforcement ratios of steel wire in the steel-plastic compound geogrid-reinforced belt were 0.63% and 11.92%, respectively.

Experimental Study on the Performance of Graded Glass Fiber Reinforced Concrete (G-GRC) Based on Engineering Application.

An important way to improve concrete performance is the use of alkali-resistant glass fibers (ARGFs) as reinforcement. This paper is based on the problems of the cracking of the partition wall and lining seepage in Laoshan Tunnel, Qingdao, China. Two types of ARGFs were selected as reinforcement materials for the partition wall and lining concrete: high dispersion (HD) and high performance (HP); and the compressive strength (CS), tensile strength (TS), flexural strength (FS), and impervious performance (IP) of concrete with different gradations of the two types of fibers were investigated. The results show that although the CS of graded glass fiber reinforced concrete (G-GRC) is slightly decreased, the TS, FS, and IP of G-GRC are significantly improved. When the densities of the ARGFs of HD and HP are 0.6 and 5 kg/m3, respectively, G-GRC performs best; additionally, compared with ordinary concrete, the TS, FS, and IP of G-GRC are increased by 15.86%, 14.90%, and 31.58%, respectively. Meanwhile, the tension-compression ratio is increased by 22.29%, and the mechanical properties of concrete are remarkably enhanced. The research results were successfully applied to the construction of the Laoshan tunnel, and good engineering results were obtained.