Development, characterization and anti-tumor effect of a sequential sustained-release preparation containing ricin and cobra venom cytotoxin.

Cobra venom cytotoxin (CVC) loaded in poly (lactide-co-glycolide) (PLGA) microspheres was mixed with ricin and encapsulated in a thermosensitive PLGA-PEG-PLGA hydrogel for this study. This sequential sustained-release preparation (SSRP) containing ricin and CVC could avoid burst release effect of CVC from microspheres. In addition, in SSRP, the two biotoxins have different drug release rates and antitumor mechanisms, which can be complementary to each other. Ricin has a faster release rate than CVC. It can combine with the tumor cell membrane and enter the cell, inhibiting protein synthesis within 2 weeks. Whereas CVC releases slowly in 5 weeks directly dissolving the tumor cell membrane and killing the cells which are less-sensitive to ricin. The in vivo experiments showed that intratumoral injection of SSRP could inhibit hepatocellular carcinoma growth significantly, and the tumor growth inhibition rate reached 73.5%. It appears that a new medicine preparation for cancer local treatment should be further studied for clinical applications.

Effect of Welding Speed on Microstructure Evolution and Mechanical Properties of Friction Stir Welded 2198 Al-Cu-Li Alloy Joints.

In the present study, 2198 Al-Cu-Li alloys were successfully friction stir welded by using various welding speed ranges of 90~180 mm/min with an invariable rotation speed of 950 r/min. The effect of welding speed on microstructure evolution and mechanical properties of the joints was investigated. The results show that, with the welding speed decreasing, the size of the nugget zone (NZ) first increases and then decreases due to different welding temperatures. At a welding speed of 150 mm/min, the size of the NZ in all joints is the biggest and the "S" curve disappears. The equiaxed grains are finer, attributed to a higher degree of dynamic recrystallization, and a larger number of fine reprecipitated phase (δ', ß' phases) particles are dispersively distributed in the NZ. Correspondingly, the joints have the highest tensile properties, and the tensile strength, yield strength and elongation are, respectively, 406 MPa, 289 MPa and 7.2%. However, compared to the base material, the tensile properties of all joints are reduced because a greater amount of δ' and ß' phases particles are dissolved in the NZ. Only the joints produced at 150 mm/min are fractured in the TMAZ with detected deep dimples and tearing ridges, and a significant necking phenomenon is observed, which indicates a complete ductile fracture mode.

Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis.

Triple-negative breast cancer (TNBC) is an aggressive histological subtype of breast cancer. It has been reported that the circular RNA (circRNA) circ-ERBB2 (circBase identifier hsa_circ_0007766) is mainly distributed in the cytoplasm of TNBC cells and promotes the proliferation and invasion of TNBC cells. This study aimed to explore the molecular mechanism of circ-ERBB2 regulating the progression of TNBC. The expression of circ-ERBB2 was detected by quantitative real-time PCR (qRT-PCR). Loss-of-function experiments were performed to investigate the function of circ-ERBB2 in TNBC cells in vitro and in vivo. The regulatory mechanism of circ-ERBB2 was surveyed by bioinformatics analysis and dual-luciferase reporter and RNA immunoprecipitation (RIP) or RNA pulldown assays. We observed that circ-ERBB2 was overexpressed in TNBC, and TNBC patients with high circ-ERBB2 expression levels had a poor prognosis. Functionally, circ-ERBB2 knockdown constrained TNBC growth in vivo, reduced the Warburg effect, accelerated apoptosis, and repressed the proliferation, migration, and invasion of TNBC cells in vitro. Mechanically, circ-ERBB2 sponged microRNA 136-5p (miR-136-5p) to elevate pyruvate dehydrogenase kinase 4 (PDK4) expression. In conclusion, circ-ERBB2 facilitated the Warburg effect and malignancy of TNBC cells by the miR-136-5p/PDK4 pathway, at least in part. This study supports circ-ERBB2 as a prognostic indicator for TNBC.

Microstructure and Mechanical Properties of 34CrNiMo6 Steel Repaired by Friction Stir Processing.

Repairing damaged parts using proper repairing methods has become an important means to reduce manufacturing and operational costs and prolong the service life of 34CrNiMo6 steel structures. In the conventional fusion repairing method, welding wire and powder are often used as filling materials. Filling materials are often expensive or difficult to find. Some metallurgical issues (such as solidification crack, higher distortion) were also found with these methods. At the same time, most of the equipment that requires welding wire and powder is expensive. In this study, a new method based on friction stir processing (FSP) was successfully employed to repair 34CrNiMo6 steel, using a block as filling material. Filling blocks are much cheaper than conventional fusion repair consumables. As a result of solid-state repair, this method can also avoid the metallurgical issues of fusion repair. The microstructure and mechanical properties of the repaired samples were investigated using OM (Optical Microscope), SEM, EDS (Energy Dispersive Spectroscopy), XRD, and a Vickers hardness electronic universal tensile tester. The results showed that 34CrNiMo6 steel was successfully repaired by this method, with no defect. Tensile tests showed that the maximum ultimate strength (UTS) was 900 MPa and could reach 91.8% of that of the substrate. The fracture mode of the tensile samples was ductile/brittle mixed fracture. Hence, the repairing method based on FSP appears to be a promising method for repairing castings.

Formation Investigation of Intermetallic Compounds of Thick Plate Al/Mg Alloys Joint by Friction Stir Welding.

5A06 Aluminum (Al) alloy and AZ31B magnesium (Mg) alloy with 20 mm thickness were successfully butt joined by friction stir welding. In order to control the composition of Al and Mg alloys along thickness direction, an inclined butt joint was designed in this study. The microstructure and phase identification at the interface of Al/Mg joints were examined using scanning electron microscopy with an energy-dispersive spectroscopy and Micro X-ray diffraction. The results indicated that there were two different formation mechanisms of intermetallic compounds at the interface of thick plate Al/Mg joint. The first was constitutional liquation, and eutectic structure consisting of Al12Mg17 and Mg solid solution existed at the top and upper-middle of the Mg side interface. The second was diffusion reaction, and the two sub-layers of Al12Mg17 and Al3Mg2 formed at the lower middle and bottom of the Mg side interface. In addition, the diffusion thickness values of Al12Mg17 and Al3Mg2 layers decreased gradually from the lower middle to bottom of the Mg side interface. As the position changes from the middle to the bottom near the Mg side interface, the diffusion coefficient of Al3Mg2 phase rapidly decreases from 3.14 × 10-12 m2/s to 6.9 × 10-13 m2/s and the diffusion coefficient of Al12Mg17 phase decreases from 6.8 × 10-13 m2/s to 1.5 × 10-13 m2/s.

The Martensitic Transformation and Mechanical Properties of Ti6Al4V Prepared via Selective Laser Melting.

This article investigated the microstructure of Ti6Al4V that was fabricated via selective laser melting; specifically, the mechanism of martensitic transformation and relationship among parent ß phase, martensite (α') and newly generated ß phase that formed in the present experiments were elucidated. The primary X-ray diffraction (XRD), transmission electron microscopy (TEM) and tensile test were combined to discuss the relationship between α', ß phase and mechanical properties. The average width of each coarse ß columnar grain is 80⁻160 µm, which is in agreement with the width of a laser scanning track. The result revealed a further relationship between ß columnar grain and laser scanning track. Additionally, the high dislocation density, stacking faults and the typical ( 10 1 ¯ 1 ) twinning were identified in the as-built sample. The twinning was filled with many dislocation lines that exhibited apparent slip systems of climbing and cross-slip. Moreover, the α + ß phase with fine dislocation lines and residual twinning were observed in the stress relieving sample. Furthermore, both as-built and stress-relieved samples had a better homogeneous density and finer grains in the center area than in the edge area, displaying good mechanical properties by Feature-Scan. The α' phase resulted in the improvement of tensile strength and hardness and decrease of plasticity, while the newly generated ß phase resulted in a decrease of strength and enhancement of plasticity. The poor plasticity was ascribed to the different print mode, remained support structures and large thermal stresses.

Chemotherapy with PLGA microspheres containing docetaxel decreases angiogenesis in human hepatoma xenograft.

To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7% and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular carcinoma. On day 21 post-treatment, the inhibition rate of tumor growth was 72.7% in the high-dose group, indicating a significant antitumor activity. Meanwhile, excellent antiangiogenic effect was observed based on the contrast-enhanced ultrasonography as well as microvessel density determination. Additionally, the real-time fluorescence quantitative PCR revealed that the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang2) genes were down-regulated significantly. Interstitial chemotherapy using PMCD was highly effective and safe for the treatment of the human hepatoma xenograft and that decreasing angiogenesis could be one of the most important mechanisms involved in the antitumor activity.