Expression of YAP suppresses cell proliferation and elevates the sensitivity of chemotherapy in retinoblastoma cells through lipid-peroxidation induced ferroptosis.

BACKGROUND: Retinoblastoma (RB) is a retinal cancer most commonly occurred in young children. Cisplatin and etoposide had been confirmed as chemotherapy drugs in the treatment of RB, even though the phenomenon of chemotherapeutic resistance has been occurring in clinical treatment frequently. RB has been reported to be a tumor with reduced expression of yes-associated protein (YAP). However, the role of YAP protein and its correlation with the chemotherapy effect in RB still remains unknown. METHODS: Here we used human RB cell lines Y79 and RB3823 to construct YAP over-expression cell lines for exploring the specific role of YAP. In vitro, a series of techniques and methods were used to identify the biological role of YAP in RB, such as Agilent Seahorse assay, lipid peroxidation assay, intracellular reactive oxygen species (ROS) measurement, flow cytometry apoptosis assay, and other basic experimental techniques, among others. RESULTS: The cell growth and cytology experimental results found YAP can inhibit the proliferation of RB cells and promote their apoptosis (Y79 32.71% vs. 3.75%; RB3823 40.32% vs. 6.73%). The mitochondrial fuel flex test, lipid peroxide and ROS measurement confirmed that YAP over-expression could promote mitochondrial fatty-acids ß-oxidation and lipid peroxidation in RB cells. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis for the expression of lipid peroxidation related factors imply that YAP over-expression caused ferroptosis in RB cell lines. In addition, YAP transcription specific activator PY-60 (10 µM) further improved the sensitivity of cisplatin/etoposide. CONCLUSIONS: Our research results found the expression of YAP inhibits cell proliferation and promoted lipid peroxidation induced ferroptosis in RB. Interestingly, the mitochondrial oxidative phosphorylation shows an increased fatty acid dependency and decreased glucose dependency. As a result, this phenomenon improved the sensitivity of RB to cisplatin/etoposide chemotherapy in vitro. Our finding provides a potential therapeutic target for RB chemotherapy.

Coupling water cycle processes with water demand routes of vegetation using a cascade causal modeling approach in arid inland basins.

Vegetation degradation is the key cause of land desertification in arid areas. Water stress is one of the most critical factors leading to vegetation degradation. The water needed for vegetation growth is inseparable from the water cycle processes. It is a new scope to reveal the vegetation water demand mechanisms from the water cycle processes. Water cycle processes in arid inland basins can be conceptually separated as RFA (runoff formation area) and RCA (runoff consumption area). In this study, both the water demand mechanisms of natural vegetation and farmland were discovered by creatively constructing the vegetation water demand route model. The TRB (Tarim River Basin), a typical arid inland basin system that RFA is separated from RCA, is considered as the study area. The tendency and relevance of water cycle factors and NDVI were detected. The dominant factors of vegetation growth were identified. According to the interaction causality of water cycle factors and vegetation, the PLS-SEM (partial least squares structural equation models) were constructed in RFA and RCA. Results displayed that SMroot (root-zone soil moisture), groundwater and precipitation were the dominant water sources for natural vegetation in RFA. The water demand for natural vegetation in RCA mainly came from SMroot and that for farmland mainly came from SMsurf (surface soil moisture). New findings showed that blue and green water circulations were more active in RFA than in RCA. Natural vegetation had better adaptability and resilience to water shortages compared with farmland. The higher effect of vegetation on AET (actual evapotranspiration) denoted the better growth status. It is contributed to the rational utilization of water resources in arid basins.

Chilling-responsive mechanisms in halophyte Puccinellia tenuiflora seedlings revealed from proteomics analysis.

Alkali grass (Puccinellia tenuiflora), a monocotyledonous perennial halophyte species, is a good pasture with great nutritional value for livestocks. It can thrive under low temperature in the saline-alkali soil of Songnen plain in northeastern China. In the present study, the chilling-responsive mechanism in P. tenuiflora leaves was investigated using physiological and proteomic approaches. After treatment of 10°C for 10 and 20days, photosynthesis, biomass, contents of osmolytes and antioxidants, and activities of reactive oxygen species scavenging enzymes were analyzed in leaves of 20-day-old seedlings. Besides, 89 chilling-responsive proteins were revealed from proteomic analysis. All the results highlighted that the growth of seedlings was inhibited due to chilling-decreased enzymes in photosynthesis, carbohydrate metabolism, and energy supplying. The accumulation of osmolytes (i.e., proline, soluble sugar, and glycine betaine) and enhancement of ascorbate-glutathione cycle and glutathione peroxidase/glutathione S-transferase pathway in leaves could minimize oxidative damage of membrane and other molecules under the chilling conditions. In addition, protein synthesis and turnover in cytoplasm and chloroplast were altered to cope with the chilling stress. This study provides valuable information for understanding the chilling-responsive and cross-tolerant mechanisms in monocotyledonous halophyte plant species.

Biosorption of C.I. Direct Blue 199 from aqueous solution by nonviable Aspergillus niger.

The capacity and mechanism with which nonviable Aspergillus niger removed the textile dye, C.I. Direct Blue 199, from aqueous solution was investigated using different parameters, such as initial dye concentration, pH and temperature. In batch experiments, the biosorption capacity increased with decrease in pH, and the maximum dye uptake capacity of the biosorbent was 29.96 mg g(-1) at 400 mg L(-1) dye concentration and 45 degrees C. The Langmuir and Freundlich models were able to describe the biosorption equilibrium of C.I. Direct Blue 199 onto the fungal biomass. Biosorption followed a pseudo-second order kinetic model with high correlation coefficients (r(2)>0.99). Thermodynamic studies revealed that the biosorption process was successful, spontaneous and endothermic in nature.