Identification of Fangchinoline as a novel autophagy inhibitor with an adjuvant of chemotherapy against lung cancer.

Autophagy is a fundamental recycling pathway that enhances cellular resilience, promoting survival. However, this survival mechanism can impede anti-cancer treatment strategies designed to induce cell death. In this study, we identified a novel autophagy inhibitor, Fangchinoline (Fan) isolated from the traditional Chinese medicine Stephania tetrandra. We speculated that when Fan blocks autophagy, cancer cells lose substantial self-preservation abilities during treatment. Firstly, we examined in detail the mechanism through which Fan inhibits autophagy. Specifically, Fan induced a significant increase in autophagosomes, as indicated by GFP-LC3 labeling, confirmed by the up-regulation of LC3-II. The autophagy receptor protein p62 was also up-regulated, suggesting a potential inhibition of autophagy flux. We further ruled out the possibility of fusion barriers between lysosomes and autophagosomes, as confirmed by their co-localization in double fluorescence staining. However, the lysosomal acid environment might be compromised, as suggested by the diminished fluorescence of acidity-sensitive dyes in the lysosomes and the corresponding decrease in mature forms of lysosomal cathepsin. To test the anti-cancer potential of Fan, we combined it with Cisplatin (Cis) or Paclitaxel (PTX) for lung cancer cell treatment. This combined treatment demonstrated a synergistically enhanced killing effect. These promising anti-tumor results were also replicated in a xenografted tumor model. The significance of this research lies in the identification of Fan as a potent autophagy inhibitor and its potential to enhance the efficacy of existing anti-cancer drugs. By unraveling the mechanisms of Fan's action on autophagy and demonstrating its synergistic effect in combination therapies, our study provides valuable insights for developing novel strategies to overcome autophagy-mediated resistance in cancer treatment.

Effect of NaNO2 Reductant Pretreatment on Low-Rank Coal Flotation.

As the reserves of high-quality coal resources in China are decreasing, it is imperative to improve the processing and comprehensive utilization of low-rank coal. In this study, NaNO2 was used for the flotation pretreatment test of the low-rank coal obtained from Majialiang, and the mechanism was discussed by contact angle analysis, zeta potential measurements, and XPS peak fitting analysis. The results showed that when the dosage of NaNO2 was 2000 g/t and the pretreatment time was 5 min, the flotation effect was the best, the ash contents of concentrate ash and tailings and the combustible recovery were 17.15, 37.12, and 42.23%, respectively; the combustible recovery increased by 12%. The contact angle, surface functional group content, and zeta potential measurements showed that with the change of NaNO2 dosage, the content of the hydrophobic functional group and the zeta potential value were consistent with the change of combustible recovery. The increase of hydrophobic functional groups can effectively enhance the hydrophobic interaction on the surface of the coal, which is conducive to the combination of collector and coal, and improve the efficiency of the collector. The NaNO2 pretreatment test can promote flotation efficiency, and the addition of reductant is an effective method for the flotation efficiency of low-rank coal in reducing oxygen-containing functional groups on the surface of low-rank coal to improve the poor floatability. In this study, the method of chemical pretreatment is put forward to provide a new idea for slime flotation.

Insight on the Void Ratio-Suction Relationship of Compacted Bentonite during Hydration.

Investigation on swelling characteristics of buffer/backfill materials during hydration is an important issue in the design of artificial barriers in high-level radioactive waste (HLW) disposal repositories. In this work, for clarifying the characteristic of void ratio-suction relationship for compacted bentonite on hydration path, suction-controlled swelling deformation tests under constant vertical stresses 0.001~40 MPa were carried out on compacted bentonite specimens. Four different types of void ratio-suction curves indicated that swelling-collapse behavior under hydration depends on suction and over-consolidation ratio (OCR), based on which the swelling index was defined. Then, equations were proposed for describing the swelling-collapse characteristic of void ratio-suction curves. Simulation results of suction-controlled swelling deformation tests show that the different types of the hydration deformation curves could be well described by the proposed equations. Obviously, the proposed equations could be used for description and prediction of swelling characteristics of compacted bentonite during hydration, which is also of great importance for the safety assessment of the HLW repositories.

Physical and Chemical Properties of Coal Gasification Fine Slag and Its Carbon Products by Hydrophobic-Hydrophilic Separation.

Coal gasification fine slag is a kind of solid waste with low resource utilization rate. The complex embedding of residual carbon and inorganic minerals (ash materials) is the main reason restricting the efficient resource separation and utilization of residual carbon or ash materials. Hydrophobic-hydrophilic separation (HHS) is a separation technology in which mineral particles with different surface hydrophobicity values are enriched in the water phase and oil phase under the action of mechanical stirring. The water on the surface of hydrophobic particles is replaced by the oil phase to form flocs, which are enriched in the hydrophobic liquid phase, while hydrophilic particles are dispersed into the aqueous phase. In this study, the HHS process was used to separate the carbon/ash from the fine gasification slag produced by a Shenning gasifier, Texaco gasifier, and GSP gasifier of Ningxia Coal Industry Co., Ltd. The physicochemical properties of the original sample and the residual carbon products obtained by hydrophobic-hydrophilic separation were analyzed. The results show that HHS can separate the carbon/ash in the three kinds of fine slag to varying degrees. The carbon element is enriched into the hydrophobic phase to form the concentrates, while the silicon element, oxygen element, and metal element enter the tailings. The spherical ash with different particle sizes distributed on the surface of residual carbon and the gap of the matrix is basically removed, while the ash in the carbon-ash melt is difficult to remove. The ash contents of the concentrate and tailings of fine slag of the Shenning gasifier are 22.58 and 96.28%, respectively, which reach the best ash index compared with that of the other two gasifiers. From the change of mineral surface properties after HHS, the distribution of oxygen-containing groups, benzene rings, Si-O, and clay minerals or carbonate minerals in the three kinds of fine slag residual carbon products is basically similar. Compared with the other two gasifier products, the GSP gasifier concentrate has a larger specific surface area and less ash material, more amorphous carbon structures (less graphitic), and more active sites, resulting in a stronger combustion activity.