a b s t r a c tZirconium is always present in Ni base superalloys as it enhances their creep properties. In the present study, the influence of very small Zr additions, 100-400 ppm, i.e. 0.01-0.04 wt.%, on hot tearing of IN738LC superalloy is experimentally investigated using dedicated turbine blade castings. Although the Zr content remains very small, it has a strong effect on hot tearing tendency. Microstructure of hot tear in as-cast samples reveal that grain size and secondary dendrite arm spacing have no significant effect on hot tearing. On the other hand eutectic phase volume fraction and its dispersion or spreading along grain boundaries drastically affect the hot tearing propensity and strongly increase with increasing amounts of Zr. Hence grain coalescence becomes impossible at grain boundaries covered with eutectic phase films. With increasing Zr content, gain coalescence between two distinct grains with no interdendritic phase requires more undercooling. Coalescence is retarded and occurs deeper in the mush zone, i.e. at lower temperatures resulting in a higher sensitivity to hot tearing. Finally, it is shown that a reduction of Zr content to 0.02 wt.% is required to fully suppress hot tearing in polycrystalline IN738LC blades.
Immune-mediated diseases (IMDs) are chronic conditions that have an immunemediated etiology. Clinically, these diseases appear to be unrelated, but pathogenic pathways have been shown to connect them. While inflammation is a common occurrence in the body, it may either stimulate a favorable immune response to protect against harmful signals or cause illness by damaging cells and tissues. Nanomedicine has tremendous promise for regulating inflammation and treating IMIDs. Various nanoparticles coated with nanotherapeutics have been recently fabricated for effective targeted delivery to inflammatory tissues. RNA interference (RNAi) offers a tremendous genetic approach, particularly if traditional treatments are ineffective against IMDs. In cells, several signaling pathways can be suppressed by using RNAi, which blocks the expression of particular messenger RNAs. Using this molecular approach, the undesirable effects of anti-inflammatory medications can be reduced. Still, there are many problems with using short-interfering RNAs (siRNAs) to treat IMDs, including poor localization of the siRNAs in target tissues, unstable gene expression, and quick removal from the blood. Nanotherapeutics have been widely used in designing siRNA-based carriers because of the restricted therapy options for IMIDs. In this review, we have discussed recent trends in the fabrication of siRNA nanodelivery systems, including lipid-based siRNA nanocarriers, liposomes, and cationic lipids, stable nucleic acid-lipid particles, polymeric-based siRNA nanocarriers, polyethylenimine (PEI)-based nanosystems, chitosan-based nanoformulations, inorganic material-based siRNA nanocarriers, and hybrid-based delivery systems. We have also introduced novel siRNA-based nanocarriers to
Bladder cancer is one of the concerning urological malignant diseases in the world, which has a clinical need for effective targeted therapy. The development of nanotechnology-based gene delivery to bladder tumor sites is an effective strategy for targeted cancer therapy with low/no toxicity. With this view, in the present work, the mesoporous silica nanoparticles (MSNs) modified with c(RGDfK)-PLGA-PEG [c(RGDfK)-MSN NPs] were constructed for co-delivery of miR-34a and siPD-L1 within bladder cancer cells and tissues. Our findings showed that miR-34a is downregulated while PD-L1 is up-regulated in cell lines and animal studies. This nano-carrier is biocompatible in the serum environment and effectively protects miR-34a and siPD-L1 against serum degradation. However, we showed that c(RGDfK)-MSN NPs could simultaneously downregulate PD-L1 expression and up-regulate miR-34a in the T24 cells and T24 mice model and enhance anti-tumor effects both in vivo and in vitro. In conclusion, these findings presented new suggestions for improving targeted therapeutic strategies with specified molecular objectives for bladder cancer treatment.
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