Raltitrexed induces apoptosis through activating ROS-mediated ER stress by impeding HSPA8 expression in prostate cancer cells.

Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N-acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy.

Comparative proteomic analysis on chloroplast proteins provides new insights into the effects of low temperature in sugar beet.

BACKGROUND: Low temperature, which is one of the main environmental factors that limits geographical distribution and sucrose yield, is a common abiotic stress during the growth and development of sugar beet. As a regulatory hub of plant response to abiotic stress, activity in the chloroplasts is related to many molecular and physiological processes, particularly in response to low temperature stress. RESULTS: The contents of chlorophyll (Chl) and malondialdehyde (MDA), relative electrical conductivity (REL), and superoxide dismutase (SOD) activity were measured. The results showed that sugar beet could manage low temperature stress by regulating the levels of Chl, REL and MDA, and the activity of SOD. The physiological responses indicated that sugar beets respond positively to low temperature treatments and are not significantly damaged. Moreover, to determine the precise time to response low temperature in sugar beet, well-known abiotic stresses-responsive transcript factor family, namely DEHYDRATION RESPONSIVE ELEMENT BINDING PROTEIN (DREB), was selected as the marker gene. The results of phylogenetic analyses showed that BvDREBA1 and BvDREBA4 were in the same branch as the cold- and drought-responsive AtDREB gene. In addition, the expression of BvDREBs reached its maximum level at 24 h after low temperature by RNA-Seq and qRT-PCR analysis. Furthermore, the changes in chloroplast proteome after low temperature at 24 h were detected using a label-free technique. A total of 416 differentially expressed proteins were identified. GO enrichment analysis showed that 16 GO terms were significantly enriched, particularly chloroplast stroma, chloroplast envelope, and chloroplast thylakoid membrane. It is notable that the transport of photosynthetic proteins (BvLTD and BvTOC100), the formation of starch granules (BvPU1, BvISA3, and BvGWD3) and the scavenging of reactive oxygen species (BvCu/Zn-SOD, BvCAT, BvPrx, and BvTrx) were the pathways used by sugar beets to respond to low temperatures at an early stage. CONCLUSIONS: These results provide a preliminarily analysis of how chloroplasts of sugar beet respond to low temperature stress at the translational level and provide a theoretical basis for breeding low temperature resistant varieties of sugar beet.

Augmented reality enabled Galilean sighting system with an adjustable reticle.

A sighting system based on the Galileo telescope structure generally suffers from the lack of a reticle, which poses great challenges to target aiming. In this work, a hybrid Galilean sighting system integrated with an augmented reality (AR) component is proposed, which produces an image of the reticle to serve as a reticle. The depth of the reticle can be adjusted flexibly to superpose with the image of the observed object. The designed system features a fourfold magnification, a large modulation transfer function (MTF)>0.3 at 40 lp/mm, and a small distortion less than 0.3% in the full field of view. The superb imaging performance combined with the targeting function of the AR reticle renders the proposed design a powerful tool in the applications of target tracking.

Manipulation of pseudo-spin guiding and flat bands for topological edge states.

Topological edge states and pseudo spins are promising paradigms to explore a new phase of matter in condensed matter physics. Here, we reveal the regulatory mechanism for guiding pseudo spin states along the interface between trivial and topological regions with elliptic cylinders made of conventional silicon material. A spin-guiding path introduced by an arrangement of elliptic cylinders exhibits high efficiency, large operation bandwidth and robustness to imperfections with tunable parameters. The pseudo spins of four types of silicon-based unit cells are measured, which may open exciting possibilities for unexpected topological properties such as flat bands. We manipulate a wide flat band with near-zero group velocities, which excites both pseudo spin up and down modes at the interface. The proposed concept might be implemented in photonic fabrication, facilitating potential applications for integrated optical devices.