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Suspenders are key components of suspension bridges and are prone to corrosion, fatigue and deck fires, resulting in damage or fracture. It is necessary to study the emergency replacement technolog...

Aconitum species, with a long history of traditional application, were applied to treat rheumatism, arthritis, stroke, and pain in Chinese medical practice. However, misuse of Aconitum species may induce central nervous toxic effects, such as numbness, vomiting, and even coma. Aconitine has been proved to be the main toxic component of Aconitum plants. Neurotoxicity is the main toxic effect of aconitine, while the underlying mechanism of aconitine remains unclear.The purpose of the study is to explore the effects and molecular mechanism of ferroptosis caused by aconitine in vivo and in vitro.Six-dpf zebrafish larvae and SH-SY5Y cells were treated with different concentrations of aconitine for 24 h. Inhibitors treatment, e.g. pretreatment with Necrostain-1 (Nec-1) and Z-VZD-FMK for 12 h, or with Ferrostain-1 (Fer-1) for 4 h, were involved in the identification of aconitine-induced ferroptosis. Transient transfection experiment was conducted to explore the effects of SLC7A11 in the process of aconitine-induced ferroptosis. The effects of aconitine on morphological changes, lipid peroxidation, ferrous ion, and ferroptosis were detected by transmission electron microscope, flow cytometry, confocal microscopy, enzyme-linked immunosorbent assay and western blotting.In SH-SY5Y cells, morphological changes including shrunken mitochondria, increased mitochondrial membranes density and ruptured mitochondrial membranes were captured in aconitine-treated group. The cell viability and GSH content dose-dependently declined, levels of lipid reactive oxygen species (ROS), malondialdehyde (MDA), and ferrous ion significantly increased after aconitine exposure for 24 h. Ferroptosis inhibitor Fer-1 pretreatment effectively increased cell viability, GSH content, and decreased levels of MDA and lipid peroxidation, suggesting that aconitine induced ferroptosis. In addition, the protein expression of SLC7A11 and GPX4 were improved after Fer-1 preincubation, which indicated that aconitine triggered ferroptosis via the inhibition of SLC7A11 and the inactivation of GPX4. Ferroptotic characteristics, including GSH depletion and lipid peroxidation accumulation, were alleviated via overexpression of SLC7A11 to increase protein expression of GPX4. In zebrafish experiment, GSH depletion, lipid peroxidation accumulation, iron overload, and the decreased protein expression of SLC7A11 and GPX4 were also induced in zebrafish larvae after aconitine exposure. Taken together, aconitine triggered ferroptotic cell death via inhibiting SLC7A11/GPX4 signal pathway in vivo and in vitro.All results indicated that aconitine triggered ferroptosis of SH-SY5Y cells and zebrafish larvae nerve cells, which involved the inhibition of SLC7A11/GPX4 signal pathway mediated by lipid peroxidation damage and iron overload.

Two-pore channels (TPCs) are cation-permeable channels located on endolysosomal membranes and important mediators of intracellular Ca2+ signalling. TPCs are involved in various pathophysiological processes, including cell growth and development, metabolism, and cancer progression. Most studies of TPCs have used TPC–/– cell or whole-animal models, or Ned-19, an indirect inhibitor. The TPC activation mechanism remains controversial, which has made it difficult to develop selective modulators. Recent studies of TPC structure and their interactomes are aiding the development of direct pharmacological modulators. This process is still in its infancy, but will facilitate future research and TPC targeting for therapeutical purposes. Here, we review the progress of current research into TPCs, including recent insights into their structures, functional roles, mechanisms of activation, and pharmacological modulators., Highlights Two-pore channel (TPC)-mediated endolysosomal Ca2+ signalling regulates a variety of processes, including cell proliferation, differentiation, metabolism, viral infection, and cardiac function. Despite the well-established model that TPCs are Ca2+-selective channels indirectly activated by nicotinic acid adenine dinucleotide phosphate (NAADP), it has also been proposed that TPCs as Na+ channels are activated directly by phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]. 3D structures of mouse TPC1 and human TPC2 were recently determined, which made it possible for structure-based virtual screening methods to identify pharmacological modulators of TPC. Recent identification by high-throughput screens of pharmacological modulators that target TPCs will help reveal the molecular mechanisms underlying the role of endolysosomal Ca2+ signalling in different pathophysiological processes, and to develop new therapeutics.

Doping of polyaniline (PANI) coatings by metal nanoparticles is a highly effective method for increasing their electrically conductive (EC), photovoltaic, and catalytic properties. In this case, the particular interest is the formation of metal-filled polyaniline coatings during their synthesis by the vacuum method. The growth of the polymer chain and the processes of structure formation proceed simultaneously and it becomes possible to vary the degree of doping, protonation, and ordering of the formed thin-film systems in a wide range. The purpose of the development is to determine the peculiarities of the formation of electron-beam dispersion from volatile products, the molecular structure of polyaniline-based layers containing noble metal nanoparticles, and to establish the effect of dopants on the molecular organization of the formed layers. The features of deposition from volatile products of electron-beam dispersion of nanocomposite polyaniline-based coatings and metal nanoparticles (silver, gold) are determined. The features of the molecular structure of the layers and the influence and its change upon the introduction of dopants by the methods of Raman and IR Fourier spectroscopy have been established. It is shown that the coatings have a conformational state of macromolecules in the form of flat extended chains, and a more oxidized structure of polyaniline layers is observed when silver chloride is used. It is shown that the features of the molecular structure of the formed polymer matrix based on polyaniline are due to the manifestation of a specific non-covalent interaction of macromolecules with metal nanoparticles. Analysis of the study results indicates the deposition possibility from the gas phase of nanocomposite conducting coatings based on polyaniline, which are a system of protonated conducting polymer chains and metal clusters. Such coatings are promising elements of sensor devices for various purposes; they can be used, in particular, in the creation of electrochromic devices.

A novel and efficient method to simulate the behavior of guidewires in the vascular system is proposed in this paper. The graph-theoretical method is based on the principle of minimal total potential energy. We formulate the total potential energy in the vascular interventional system as the summation of the elastic energy of the guidewire and the energy due to the deformation of the vessel wall. A graph is constructed with low complexity ensuring the efficiency of the single source shortest path. Compared to previous results, experiments in three phantoms have been conducted to evaluate the performance of the proposed method and the results demonstrate that our method can achieve 20% improvement with faster running time.