Macromolecular proton fraction as a myelin biomarker: principles, validation, and applications

Macromolecular proton fraction (MPF) is a quantitative MRI parameter describing the magnetization transfer (MT) effect and defined as a relative amount of protons bound to biological macromolecules with restricted molecular motion, which participate in magnetic cross-relaxation with water protons. MPF attracted significant interest during past decade as a biomarker of myelin. The purpose of this mini review is to provide a brief but comprehensive summary of MPF mapping methods, histological validation studies, and MPF applications in neuroscience. Technically, MPF maps can be obtained using a variety of quantitative MT methods. Some of them enable clinically reasonable scan time and resolution. Recent studies demonstrated the feasibility of MPF mapping using standard clinical MRI pulse sequences, thus substantially enhancing the method availability. A number of studies in animal models demonstrated strong correlations between MPF and histological markers of myelin with a minor influence of potential confounders. Histological studies validated the capability of MPF to monitor both demyelination and re-myelination. Clinical applications of MPF have been mainly focused on multiple sclerosis where this method provided new insights into both white and gray matter pathology. Besides, several studies used MPF to investigate myelin role in other neurological and psychiatric conditions. Another promising area of MPF applications is the brain development studies. MPF demonstrated the capabilities to quantitatively characterize the earliest stage of myelination during prenatal brain maturation and protracted myelin development in adolescence. In summary, MPF mapping provides a technically mature and comprehensively validated myelin imaging technology for various preclinical and clinical neuroscience applications

Mathematical models describing the absorption mechanism of cadmium ions on the modified peat sorbent

The sorption mechanism of cadmium ions on the modified fen peat is investigated. The kinetic, equilibrium, and thermodynamic parameters of the process are calculated; kinetic equations and the diffusion sorption model are described. It is shown that the absorption process of cadmium ions from an aqueous solution is carried out by two sorption centers and follows the Langmuir law; the absorption mechanism is diffusional and is described by the anti-Yander model

Mathematical models describing the absorption mechanism of cadmium ions on the modified peat sorbent

The sorption mechanism of cadmium ions on the modified fen peat is investigated. The kinetic, equilibrium, and thermodynamic parameters of the process are calculated; kinetic equations and the diffusion sorption model are described. It is shown that the absorption process of cadmium ions from an aqueous solution is carried out by two sorption centers and follows the Langmuir law; the absorption mechanism is diffusional and is described by the anti-Yander model

5‑Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

Tyrosyl–DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)–DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound <b>8</b>. Through structure–activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound <b>50</b> as a submicromolar inhibitor of Tdp1 (IC₅₀ = 0.87 μM). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition