Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

Drug resistance is still an obstacle in cancer therapy, leading to the failure of tumor treatment. The emergence of tumor drug resistance has always been a main concern of oncologists. Therefore, overcoming tumor drug resistance and looking for new strategies for tumor treatment is a major focus in the field of tumor research. Natural products serve as effective substances against drug resistance because of their diverse chemical structures and pharmacological effects. We reviewed the signaling pathways involved in the development of tumor drug resistance, including Epidermal growth factor receptor (EGFR), Renin-angiotensin system (Ras), Phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), Wnt, Notch, Transforming growth factor-beta (TGF-β), and their specific signaling pathway inhibitors derived from natural products. This can provide new ideas for the prevention of drug resistance in cancer therapy.     

孔梯度陶瓷纤维复合膜管的制备及特性

陶瓷过滤管具有孔隙率高、耐腐蚀、耐高温、机械强度高、便于清洗、使用寿命长等优点,是高温烟尘处理用的高效过滤元件.本文研制了一种具有梯度孔结构堇青石陶瓷纤维复合膜过滤元件,该过滤元件是由多孔支撑体、过渡层和分离膜层组成.其中支撑体、过渡层和分离层的气孔率分别为35～40;、50～60;和60～70;.文中主要分析了孔梯度陶瓷纤维复合膜管的材料结构和抗热震性能,同时对复合膜管进行含尘气体过滤的冷态模拟试验.对于烟气中粒径大于或等于0.1μm的颗粒,复合膜管的截留率达到99.8;以上.     

Laser cladding of copper with molybdenum for wear resistance enhancement in electrical contacts

Laser cladding of Mo on Cu has been attempted with the aim of enhancing the wear resistance and hence increasing the service life of electrical contacts made of Cu. In order to overcome the difficulties arising from the large difference in thermal properties and the low mutual solubility between Cu and Mo, Ni was introduced as an intermediate layer between Mo and Cu. The Ni and Mo layers were laser clad one after the other to form a sandwich layer of Mo/Ni/Cu. Excellent bonding between the clad layer and the Cu substrate was ensured by strong metallurgical bonding. The hardness of the surface of the clad layer is seven times higher than that of the Cu substrate. Pin-on-disc wear tests consistently showed that the abrasive wear resistance of the clad layer was also improved by a factor of seven as compared with untreated Cu substrate. The specific electrical contact resistance of the clad surface was about 5.6 × 10⁻⁷ Ω cm².     

Role of Intracellular Iron in Switching Apoptosis to Ferroptosis to Target Therapy-Resistant Cancer Stem Cells

Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.     

Aggregation of clay platelets in nematic liquid crystal, 5CB: microstructure,electrical conductivity and rheological investigations

The microstructure, electrical conductivity and rheological properties of a nematic liquid crystal (5CB) doped at concentrations up to 4.5 wt% of montmorillonite (MMT) or organomontmorillonite (OMMT) clay nanoplatelets, were investigated at temperatures between 293 and 310 K. Microscopy and electrical conductivity assessment revealed noticeable differences in aggregation in MMT and OMMT suspensions, MMT nanoplatelets showing a strong tendency to aggregation. The incubation of 5CB in the presence of MMT initially produced loose aggregation, followed by the formation of compact aggregates. The latter had practically no influence on the surrounding inter-aggregate regions. In the case of OMMT, a greater degree of integration of the nanoplatelets was observed within the liquid crystal structure of 5CB, resulting in a noticeable effect on electrical conductivity and activation energy of the composite material. Thixotropy was observed in suspensions of 5CB composites formed with either MMT or OMMT. A composite of 5CB with OMMT also exhibited anomalous viscous thinning at shear rates below 100 s^?1. A structural model is suggested to explain this behaviour.     

Study on the flow resistance of the dispersion system of deformable preformed particle gel in porous media using LBM-DEM-IMB method

After being injected into the porous media, the dispersion system of preformed particle gel (PPG) tends to enter high permeability regions and block water channeling passages, which forces the subsequent water to turn to the low permeability regions and thus increases sweep efficiency and enhances oil recovery. However, it is still unclear about the influence factors and the mechanisms how PPG increases water flow resistance, which limits the application of PPG in more oilfields. Therefore, the paper combines the lattice Boltzmann method (LBM), the discrete element method (DEM) and the improved immersed moving boundary (IMB) method to simulate the migration of deformable PPG in porous media. On the basis, the paper quantitatively analyzes the variation law of displacement pressure across the porous media and discusses the influence factors such as the PPG diameter, elasticity modulus and the number concentration. Results indicate that, because of the friction and retention of PPG in pore-throat, the displacement pressure across the porous media during PPG flooding is much higher than that during water flooding. In other words, the existence of PPG increases the flow resistance of injected water. Besides, the displacement pressure is always fluctuant resulting from the continuous process of PPG migration, retention, deformation and remigration. Influence factor analysis shows that the incremental value and fluctuation degree of flow resistance increase with the PPG diameter, elasticity modulus and the number concentration. The study not only provides useful reference for future PPG flooding, but also benefits the development of deformable particle flow theory.     

Preparation of modified polymer blend and electrical performance

In this study, a modified binary polymer blend made up of polycarbonate and polystyrene blend has been prepared by loading of aluminum oxide (Al₂O₃) as a dopant. The role of alumina with polymer blend system was addressed in view of interfacing criteria. The filler concentration of modified blend was taken as 5, 10, and 15%. The morphological, thermal, and electrical properties were characterized by various techniques. Optical microscopy confirms the homogenous dispersion of Al₂O₃ in blend. The presence of alumina was detected by subatomic level using atomic force microscope (both two and three dimensional approach). The differential scanning calorimetric thermographs demonstrate decreasing softing point as function of alumina loading. The dielectric properties such as dielectric constant, loss, and electrical modulus were studied under DC bias. The effect of DC bias exhibits significant changes at low amount of Al₂O₃. The dielectric polarization supports Maxwell Wagner (MW) theory due to low frequency response. 15% Al₂O₃ gives the highest dielectric constant (ε′) value (3.5?×?10⁵) at 10 Hz. The polymer modified blend with Al₂O₃ may be used as a one of the best dielectric medium.     

Multiple Keys for a Single Lock: The Unusual Structural Plasticity of the Nucleotidyltransferase (4′)/Kanamycin Complex

The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme‐catalysed chemical modification of the drug. Over the last two decades, significant efforts in medicinal chemistry have been focused on the design of non‐ inactivable antibiotics. Unfortunately, this strategy has met with limited success on account of the remarkably wide substrate specificity of aminoglycoside‐modifying enzymes. To understand the mechanisms behind substrate promiscuity, we have performed a comprehensive experimental and theoretical analysis of the molecular‐recognition processes that lead to antibiotic inactivation by Staphylococcus aureus nucleotidyltransferase 4′(ANT(4′)), a clinically relevant protein. According to our results, the ability of this enzyme to inactivate structurally diverse polycationic molecules relies on three specific features of the catalytic region. First, the dominant role of electrostatics in aminoglycoside recognition, in combination with the significant extension of the enzyme anionic regions, confers to the protein/antibiotic complex a highly dynamic character. The motion deduced for the bound antibiotic seem to be essential for the enzyme action and probably provide a mechanism to explore alternative drug inactivation modes. Second, the nucleotide recognition is exclusively mediated by the inorganic fragment. In fact, even inorganic triphosphate can be employed as a substrate. Third, ANT(4′) seems to be equipped with a duplicated basic catalyst that is able to promote drug inactivation through different reactive geometries. This particular combination of features explains the enzyme versatility and renders the design of non‐inactivable derivatives a challenging task.     

Optimal Operations Management and Network Planning of a District Heating System with a Combined Heat and Power Plant

District heating plants are becoming more common in European cities. These systems make it possible to furnish users with warm water while locating the production plants in the outskirts having the double benefit of lowering the impact of pollution on the center of the city and achieving better conversion performances. In order to amortize the costs throughout the year, the system often includes a combined heat and power (CHP) plant, to exploit the energy during the summer as well, when the demand for warm water decreases. A linear programming model for the optimal resource management of such a plant is presented and some results for a real case are reported. A distribution network design problem is also addressed and solved by means of mixed integer linear programming.