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Objective To investigate the molecular mechanism of SNHG5 regulating the proliferation, invasion and apoptosis of glioblastoma multiforme (GBM) cells by targeting miR-421. Methods Real-time quantitative PCR test was performed to detect the expression levels of SNHG5 and miR-421 in 31 cases of GBM tissue samples and 32 cases of normal brain tissue samples. After increasing or decreasing SNHG5 expression in U87 cell lines by lentivirus or plasmid transfection, the changes of miR-421 expression were measured by real-time quantitative PCR, to explore the correlation between SNHG5 and miR-421 in GBM. The dual-luciferase reporter test was performed to explore the target interaction of SNHG5 and miR-421. The plasmids with low expression of SNHG5 and miR-421 were cotransfected into U87 cells for the rescue experiment. CCK-8 test, Transwell test, flow cytometry and tumor cell xenograft in nude mice were used to verify molecular mechanism of SNHG5 regulating the proliferation, invasion and apoptosis of GBM in vitro and vivo. Results The expression level of miR-421 was decreased in U87 cell line after SNHG5 upregulation. In addition, the expression level of miR-421 was increased in U87 cell line after SNHG5 downregulation (P < 0.05). The expression level of SNHG5 was correlated negatively with the expression of miR-421 in GBM and U87 cell line. The result of luciferase reporter tests indicated SNHG5 targetedly interacted with miR-421. Rescue experiment results showed that compared with si-SNHG5+miR-421-inhibitor group, the proliferation, invasion and anti-apoptosis ability of U87 cells were significantly inhibited in the si-SNHG5+control-inhibitor group, the expression levels of BAX and p21 were significantly higher, the expression levels of CyclinD1 and Bcl-2 were lower remarkably (P < 0.05). Conclusion SNHG5 promotes the proliferation, invasion and anti-apoptosis of GBM by targeting miR-421 and regulating the expression of CyclinD1, p21, BAX and Bcl-2. Downregulation of miR-421 is related to SNHG5 overexpression in GBM.

Objective To investigate the reasons of HOXA5 overexpression in GBM and the molecular mechanism of miR-128-3p regulating the proliferation, invasion and apoptosis of glioblastoma multiforme. Methods After increasing and decreasing miR-128-3p expression in U87 cell lines by lentivirus transfection, the changes of HOXA5 expression were detected by Western blot, to explore the correlation between miR-128-3p and HOXA5 in GBM. The dual-luciferase reporter tests were performed to detect the target interaction of miR-128-3p with HOXA5. Through CCK-8 test, Transwell test, flow cytometric assay and tumor cell xenograft in nude mice, we verified molecular mechanism of miR-128-3p regulating the proliferation, invasion and apoptosis of GBM in vitro and in vivo. Results The expression level of HOXA5 was decreased in U87 cell line after miR-128-3p upregulation. In addition, the expression level of HOXA5 was increased in U87 cell line after miR-128-3p downregulation (P < 0.05). The expression level of HOXA5 was correlated negatively with the expression of miR-128-3p in U87 cell lines. MiR-128-3p targetedly interacted with 3'UTR of HOXA5 and inhibited the expression of HOXA5. The proliferation, invasion and anti-apoptosis of U87 cells were significantly decreased in the miR-128-3p+control group. Conclusion MiR-128-3p regulates negatively the proliferation, invasion and anti-apoptosis of GBM cells by targeting HOXA5. The overexpression of HOXA5 is induced by downregulation of miR-128-3p in GBM.

Due to the transient interaction between laser and powder and layer-by-layer rapid melting and solidification, laser additive manufacturing-fabricated metal components can exhibit unique microstructure evolution behaviors and strengthening mechanisms that are normally not available in traditional processes. In this work, a previously unreported rapid hardening behavior at the very early stage of isothermal aging for laser powder bed fusion-processed high-strength Al-5024 alloy was revealed. The microstructures and mechanical properties of specimens aged from 10 min to 120h were systematically analyzed. It showed that the specimens underwent two peak hardening processes during an isothermal aging at 325 °C. The mechanical properties of the specimens including microhardness, yield strength, and elastic modulus were significantly enhanced after an extremely short aging time of 10 min and then reached a secondary peak hardening at an aging time of 4h, where the yield strength of 450 ± 10.3 and 463.2 ± 13.2 MPa were obtained, respectively. The unusual aging responses were attributed to the formation and decomposition of Sc-rich clusters with a high number density of 2.7 × 1023 m−3 and nano-size of 2.71 nm. These clusters were characterized by transmission electron microscopy analyses and further supported by differential scanning calorimetry measurements, where a significantly higher activation energy of 147.6 ± 21.1 kJ/mol corresponding to the precipitation/coarsening process of Al3(Sc,Zr) was measured for rapid hardening specimens. In addition, the relationship between the aging process, the evolution of nano-precipitates, and the mechanical properties was systematically demonstrated. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and clinical significance of ZMYND11 in glioblastoma multiforme(GBM). Methods The tumor samples(tumor group) and non-neoplasm brain tissue(control group) were collected intraoperatively from 20 cases of GBM and 20 patients with severe brain injury in the Second Hospital of Hebei Medical University. The difference of ZMYND11 expression between two groups was determined using qRT-PCR and Western blot. U87 cells with upregulated ZMYND11 expression was constructed using transfection of ZMYND11-overexpression lentivirus. CCK, Transwell assay and flow cytometry were performed to identify the role of ZMYND11 in the proliferation, invasion and apoptosis of U87 cells. U87 cells with ZMYND11 overexpression were inoculated into nude mice for in vivo experiment. Results The expression levels of ZMYND11 mRNA and protein were lower in GBM tissues than those in non-neoplasm brain tissues(P < 0.001). In vitro, ZMYND11 inhibited effectively the proliferation and invasion, as well as promoted the apoptosis of U87 cells. In vivo, ZMYND11 suppressed remarkably the growth of graft tumor. Conclusion ZMYND11 inhibits the development and progression of GBM.

To overcome the disadvantages of comparatively poor surface hardness and deprived resistance against wear of Ti–6Al–4V alloy, the protective NiTi coatings are fabricated at different processing parameters by laser‐directed energy deposition (LDED). This work presents a comprehensive study of deposition morphology, phase constituents, microstructural evolution, composition distribution, and mechanical properties of as‐fabricated NiTi deposition tracks. The relationship among processing parameters and deposition morphology, phase constituents, and mechanical properties is established. The microstructural evolution mechanism and the composition distribution on the cross section of deposition tracks are revealed. Results show that the deposition tracks are successfully formed under all laser processing parameters, and the dilution ratio increases with the increase in laser power and scanning speed. The deposition tracks consist of NiTi2, NiTi, and α–Ti. According to the microstructural analysis, planar crystals are formed between the substrate and the deposition tracks, and columnar and equiaxed dendrites are found in the deposition tracks. The average microhardness increases continuously with the increase in laser power. The deposition track prepared at laser power of 1400 W has the highest average microhardness of 732.45 HV0.2. The deposition track at this laser power exhibits excellent wear properties, with a wear rate of 2.25 × 10−6 mm3 Nm−1. [ABSTRACT FROM AUTHOR]

Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome‐coated doxorubicin (DOX)‐loaded nanoparticles (ENPDOX) in BBB penetration, inducing immunogenic cell death (ICD) and promoting survival of GBM‐bearing mice. DOX‐loaded nanoparticles (NPDOX) were coated with exosomes prepared from mouse brain endothelial bEnd.3 cells. ENPDOX cellular uptake was examined. Penetration of ENPDOX through the BBB was tested in an in vitro transwell system and a GBM mouse model. The effects of ENPDOX in inducing apoptosis and ICD were assessed. Finally, the efficacy of ENPDOX in the treatment of GBM‐bearing mice was assessed. ENPDOX was taken up by bEnd.3 cells and could penetrate the BBB both in vitro and in vivo. In vitro, ENDDOX induced apoptosis and ICD of glioma GL261 cells. Systemic administration of ENPDOX resulted in maturation of dendritic cells, activation of cytotoxic cells, altered production of cytokines, suppressed proliferation and increased apoptosis of GBM cells in vivo and prolonged survival of GBM‐bearing mice. Our findings indicate that ENPDOX may be a potent therapeutic strategy for GBM which warrants further investigation in clinical application. [ABSTRACT FROM AUTHOR]