OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.     

Platinum(II) Complexes Bearing Triphenylphosphine and Chelating Oximes: Antiproliferative Effect and Biological Profile in Resistant Cells

Platinum(II) complexes of the type [Pt(Cl)(PPh₃){(κ²-N,O)-(1{C(R)=N(OH)-2(O)C₆H₄})}] with R=Me, H, ( 1 and 2 ) were synthesized and characterized. Single-crystal X-ray diffraction confirmed the proposed (SP4-3) configuration for 1 . Study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the more effective. In particular, it showed a remarkable cytotoxicity in ovarian carcinoma cells (A2780) and interestingly, a significant antiproliferative effect on cisplatin resistant cells (A2780cis). Investigation into the intracellular mechanism of action demonstrated that 2 had a lower ability to platinate DNA than did cisplatin, which was taken as reference, and a notably higher uptake in resistant cells. A significant accumulation in mitochondria, along with the ability to induce concentration-dependent mitochondrial membrane depolarization and intracellular reactive oxygen species production, allowed us to propose a mitochondrion-mediated pathway as responsible for the interesting cytotoxic profile of complex 2 .     

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

A novel and straightforward synthesis of highly substituted isoquinoline‐5,8‐dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag₂CO₃ promoted, 1,3‐dipolar cycloaddition of C‐heteroaryl‐N‐aryl nitrilimines and substituted isoquinoline‐5,8‐diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC₅₀ values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.     

Ice adhesion on different microstructure superhydrophobic aluminum surfaces

The adhesion of ice to high -voltage overhead transmission lines should be small to ensure ease of ice shedding under small external forces. In this work, we studied the influence of the microstructure of superhydrophobic surfaces on the strength of ice adhesion at a working temperature of ?6?°C. Compared to a bare aluminum surface, the microstructure superhydrophobic aluminum surfaces did decrease ice adhesion strength. The superhydrophobic aluminum surfaces with a larger number of micro-holes produced the lowest strength of ice adhesion; its ice adhesion strength was ～163.8 times lower than that for the bare aluminum samples. Furthermore, such microstructure aluminum surfaces had water contact angles larger than 150° and water sliding angles of less than 8.2° even at a working temperature of ?6?°C. The low values of the ice adhesion strength of the above samples were mainly attributed to the superhydrophobic property, which was obtained by creating a structure of micro-nanoscale holes on the aluminum surface after treatment with a low- surface-energy fluoroalkylsilane (FAS).     

Spark-plasma-sintering temperature dependence of structural and piezoelectric properties of BNT–BT<Subscript>0.08</Subscript> nanostructured ceramics

(Bi_0.5Na_0.5)TiO₃ doped with 8 mol% BaTiO₃ powder prepared by sol–gel was compacted and sintered by spark-plasma-sintering method. The influence of spark-plasma-sintering temperature on the densification and piezoelectric properties of these ceramics was studied. Starting from BNT–BT_0.08 powder gel with a microstructure consisting of particles with average size of 50 nm, ceramics with grain size of 60–90 nm and density of about 98.9–99.6% of the theoretical density were obtained by spark-plasma-sintering at 800–900 °C. Increasing the sintering temperature by SPS from 800 to 900 °C lead to the increase of d ₃₃, k _p, ε₃₃^T and, decrease of Q _m. Typical d ₃₃ and k _p values of BNT–BT_0.08 ceramics sintered by spark-plasma-sintering at 900 °C were 8 and 0.029, respectively.     

Strategies for Successful Over-Expression of Human Membrane Transport Systems Using Bacterial Hosts: Future Perspectives

Ten percent of human genes encode for membrane transport systems, which are key components in maintaining cell homeostasis. They are involved in the transport of nutrients, catabolites, vitamins, and ions, allowing the absorption and distribution of these compounds to the various body regions. In addition, roughly 60% of FDA-approved drugs interact with membrane proteins, among which are transporters, often responsible for pharmacokinetics and side effects. Defects of membrane transport systems can cause diseases; however, knowledge of the structure/function relationships of transporters is still limited. Among the expression of hosts that produce human membrane transport systems, E. coli is one of the most favorable for its low cultivation costs, fast growth, handiness, and extensive knowledge of its genetics and molecular mechanisms. However, the expression in E. coli of human membrane proteins is often toxic due to the hydrophobicity of these proteins and the diversity in structure with respect to their bacterial counterparts. Moreover, differences in codon usage between humans and bacteria hamper translation. This review summarizes the many strategies exploited to achieve the expression of human transport systems in bacteria, providing a guide to help people who want to deal with this topic.     

憎水涂层对铝单丝表面覆冰性能的影响

为研究憎水性涂层对铝单丝表面覆冰性能的影响,在低温过冷水条件下,利用实验室导线覆冰模拟系统试验研究了不同憎水性铝单丝表面覆冰的形成过程.研究发现:用普通憎水涂层涂覆铝单丝虽不能抑制表面覆冰的形成和增长,但可以延缓表面覆冰层的形成时间;硬脂酸涂覆制备的超憎水铝单丝表面可以有效抑制表面覆冰的形成和增长.分析表明:普通憎水性表面可以抑制表面附着水滴的湿润和扩散,但表面附着水滴与涂层间的作用力较大,水滴滑行角较大,水滴小易滑落表面:硬脂酸涂覆制备的超憎水铝单丝表面具有特殊的微纳米结构和较小的水滴滑行角,不利于水滴的粘附和冻结.     

配电变压器雷击建模及雷电防护

配电变压器(简称配变)作为配网的重要组成部分,绝缘水平低,易遭受雷电过电压的侵害,其安全运行对配电网稳定性及可靠性具有十分重要的意义。采用散射参数测量法,测量配变散射参数并经数据处理获得配变的阻抗幅频特性,经电路拟合构建了适用于雷击情况的配变宽频模型,并经基于模拟退火法的粒子群算法对等效电路参数进行优化,实测结果表明配变实际输出响应与文中宽频模型仿真结果吻合度较高。基于该宽频模型分析了冲击电晕对配变过电压传播的影响以及配变防雷保护措施,结果表明冲击电晕显著减小配变过电压幅值,配变低压侧加装避雷器对其防雷作用明显。     

Artificial-turf playing fields: contents of metals, PAHs, PCBs, PCDDs and PCDFs, inhalation exposure to PAHs and related preliminary risk assessment

The artificial-turf granulates made from recycled rubber waste are of health concern due the possible exposure of users to dangerous substances present in the rubber, and especially to PAHs. In this work, we determined the contents of PAHs, metals, non-dioxin-like PCBs (NDL-PCBs), PCDDs and PCDFs in granulates, and PAH concentrations in air during the use of the field. The purposes were to identify some potential chemical risks and to roughly assess the risk associated with inhalation exposure to PAHs. Rubber granulates were collected from 13 Italian fields and analysed for 25 metals and nine PAHs. One further granulate was analysed for NDL-PCBs, PCDDs, PCDFs and 13 PAHs. Air samples were collected on filter at two fields, using respectively a high volume static sampler close to the athletes and personal samplers worn by the athletes, and at background locations outside the fields. In the absence of specific quality standards, we evaluated the measured contents with respect to the Italian standards for soils to be reclaimed as green areas. Zn concentrations (1 to 19 g/kg) and BaP concentrations (0.02 to 11 mg/kg) in granulates largely exceeded the pertinent standards, up to two orders of magnitude. No association between the origin of the recycled rubber and the contents of PAHs and metals was observed. The sums of NDL-PCBs and WHO-TE PCDDs + PCDFs were, respectively, 0.18 and 0.67 × 10^− 5 mg/kg. The increased BaP concentrations in air, due to the use of the field, varied approximately from < 0.01 to 0.4 ng/m³, the latter referring to worst-case conditions as to the release of particle-bound PAHs. Based on the 0.4 ng/m³ concentration, an excess lifetime cancer risk of 1 × 10^− 6 was calculated for an intense 30-year activity.