Discovery of Novel Ortho-Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

Design, synthesis, and biological evaluation of 2-amino-6-methyl-phenol derivatives targeting lipid peroxidation with potent anti-ferroptotic activities.

The suppression of ferroptosis is emerging as a promising therapeutic strategy for effectively treating a wide range of diseases, including neurodegenerative disorders, organ ischemia-reperfusion injury, and inflammatory conditions. However, the clinical utility of ferroptosis inhibitors is significantly impeded by the limited availability of rational drug designs. In our previous study, we successfully unraveled the efficacy of ferrostatin-1 (Fer-1) attributed to the synergistic effect of its ortho-diamine (-NH) moiety. In this study, we present the discovery of the ortho-hydroxyl-amino moiety as a novel scaffold for ferroptosis inhibitors, employing quantum chemistry as well as in vitro and in vivo assays. 2-amino-6-methylphenol derivatives demonstrated remarkable inhibition of RSL3-induced ferroptosis, exhibiting EC50 values ranging from 25 nM to 207 nM. These compounds do not appear to modulate iron homeostasis or lipid reactive oxygen species (ROS) generation pathways. Nevertheless, they effectively prevent the accumulation of lipid peroxides in living cells. Furthermore, compound 13 exhibits good in vivo activities as it effectively protect mice from kidney ischemia-reperfusion injury. In summary, compound 13 has been identified as a potent ferroptosis inhibitor, warranting further investigation as a promising lead compound.

Endogenous chemicals guard health through inhibiting ferroptotic cell death.

Ferroptosis is a new form of regulated cell death caused by iron-dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine-glutathione-glutathione peroxidase 4 system (cyst(e)ine-GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH4) system (GCH1/BH4 system), ferroptosis suppressor protein 1/coenzyme Q10 system (FSP1/CoQ10 system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q10 (CoQ10), BH4, hydropersulfides, vitamin K, vitamin E, 7-dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors.

Scattering characteristics of a terahertz Bessel vortex beam by 3D dielectric-coated targets.

In order to explore the application of terahertz (THz) vortex beams in 3D dielectric-coated target detection and imaging, scattering characteristics of a THz Bessel vortex beam by 3D dielectric-coated conducting targets are investigated in terms of the combination of planewave angular spectrum expansion and a physics optics method in this paper. The accuracy of the proposed method is verified by comparing with the results of FEKO software. The scattering characteristics of a THz Bessel vortex beam by several typical 3D dielectric-coated targets are analyzed in detail. The effects of the beam parameters (topological charge, half-cone angle, incident angle and frequency) are discussed. The results show that with an increase of topological charge, the magnitude of the radar cross section (RCS) decreases, and the maximum value moves away from the incident direction gradually; the distribution of the RCS does not keep symmetry as the incident angle increases, and the corresponding orbital angular momentum state distribution of the far-scattered field is distorted remarkably.

[Vertical Pollution Characteristics and Sources of Polycyclic Aromatic Hydrocarbons in a Heterogeneous Unsaturated Zone Under a Coking Plant].

Six deep sampling boreholes are used for studying the sources and vertical distribution of 16 polycyclic aromatic hydrocarbons (PAHs) in an abandoned coking plant. The maximum depth of soil sampling ranged from 9.5-42 m. The present study analyzes the distribution characteristics and sources of PAHs in addition to the important factors affecting migration of PAHs in the unsaturated zone. Results showed that the maximum values of total PAHs range of 134.79-11266.81 mg·kg-1 at vertical depths ranging from 1-5 m. We found that 2+3 rings dominated total PAHs and that the highest content was Nap. Results also showed that the main source of PAH pollution was coal combustion. Coal tar pitch and different oils from deep processing of tar played an important role in PAH pollution. The gravel layer served as a good infiltration channel for pollutants, and the sand lens below 20 m depth became the main enrichment layer for PAHs through adsorption and interception. Oils and wastewater from discharge and leaching of chemicals contributed to the migration of PAHs through inter-miscibility and competitive adsorption, which led to deep soil pollution. Soil layers above 1 m depth were affected by artificial disturbance, rainfall leaching, and degradation, and the unsaturated zone below 30 m depth was affected by leaching from groundwater. Consequently, the ratio of low to high rings first increased before decreasing with increased depth of the unsaturated zone. The types of pollution sources, rock particle sizes, organic matter content, and hydrogeological conditions all affected the vertical distribution and migration of PAHs.

Design, fabrication, and measurement of an anisotropic holographic metasurface for generating vortex beams carrying orbital angular momentum: erratum.

This erratum makes corrections to Eqs. (7) and (9) of Opt. Lett.44, 1452 (2019).OPLEDP0146-959210.1364/OL.44.001452.

Design, fabrication, and measurement of an anisotropic holographic metasurface for generating vortex beams carrying orbital angular momentum.

In this Letter, to the best of our knowledge, a novel anisotropic surface impedance holographic metasurface antenna for generating orbital angular momentum (OAM) is developed through design, fabrication, and measurement at radio frequencies. The classical leaky-wave theory and a microwave holography method are combined to realize vortex waves carrying different OAM modes flexibly. The holographic metasurface composed of subwavelength quasi-periodic anisotropic metallic patches on a grounded dielectric substrate operates by exciting the interference patterns. The interferences are generated between a reference wave excited by the monopole antenna and a field with the desirably shaped wavefront-carrying helical phase. Numerical simulation has shown good agreement with the experimental results, which lays a solid foundation for holographic metasurface antennas having the potential for OAM generation at radio frequencies.

Dual-polarized reflectarray for generating dual beams with two different orbital angular momentum modes based on independent feeds in C- and X-bands.

In this paper, a dual-band dual-polarized reflectarray for generating dual beams with respect to carrying two different orbital angular momentum (OAM) topological charges operating in the C-band in horizontal polarization and in the X-band in vertical polarization is proposed, with two separate horns performing on the two proposed bands as the feeding. The proposed reflectarray consists of two band reflective element cells operating in two orthogonal directions. Owing to the two composing elements orthogonally interleaved on the reflectarray surface, the corresponding phase compensation performance in one band can be slightly affected by the elemental resonance in another band; thus, the degree of the coupling between the elements with different-band operations can be neglected, resulting in fairly independent phase compensation. In other words, the desired OAM generation reflectarray, to some extent, can be developed based on two different frequency band OAM reflectarrays at the same aperture. In addition, simulations and measurements strongly suggest the feasibility and the validity of the approach, which provides a solid foundation for the application of multi-band reflectarrays to the multi-OAM-mode generation.