In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17$\alpha$-hydroxylase), 3$\beta$-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

Glycidyl azide polymer (GAP), an energetic binder, is the focus of this review. We briefly introduce the key properties of this well-known polymer, the difference between energetic and non-energetic binders in propellant and explosive formulations, the fundamentals for producing GAP and its copolymers, as well as for curing GAP using different types of curing agents. We use recent works as examples to illustrate the general approaches to curing GAP and its derivatives, while indicating a number of recently investigated curing agents. Next, we demonstrate that the properties of GAP can be modified either through internal (structural) alterations or through the introduction of external (plasticizers) additives and provide a summary of recent progress in this area, tying it in with studies on the properties of such modifications of GAP. Further on, we discuss relevant works dedicated to the applications of GAP as a binder for propellants and plastic-bonded explosives. Lastly, we indicate other, emerging applications of GAP and provide a summary of its mechanical and energetic properties.

The gonadal steroids, including androgens, estrogens and progestogens, are involved in the control of body fat distribution in humans. Nevertheless, not only the size and localization of the fat depots depend on the sex steroids levels, but they can also highly affect the functioning of adipose tissue. Namely, the gonadocorticoids can directly influence insulin signaling, lipid metabolism, fatty acid uptake and adipokine production. They may also alter energy balance and glucose homeostasis in adipocytes in an indirect way, e.g., by changing the expression level of aquaglyceroporins. This work presents the recent advances in understanding the molecular mechanism of how the gonadal steroids influence the functioning of adipose tissue leading to a set of detrimental metabolic consequences. Special attention is given here to highlighting the sexual dimorphism of adipocyte functioning in terms of health and disease. Particularly, we discuss the molecular background of metabolic disturbances occurring in consequence of hormonal imbalance which is characteristic of some common endocrinopathies such as the polycystic ovary syndrome. From this perspective, we highlight the potential drug targets and the active substances which can be used in personalized sex-specific management of metabolic diseases, in accord with the patient’s hormonal status.

Several approaches to ion-channel gating modelling have been proposed. Although many models describe the dwell-time distributions correctly, they are incapable of predicting and explaining the long-term correlations between the lengths of adjacent openings and closings of a channel. In this paper we propose two simple random-walk models of the gating dynamics of voltage and Ca²⁺-activated potassium channels which qualitatively reproduce the dwell-time distributions, and describe the experimentally observed long-term memory quite well. Biological interpretation of both models is presented. In particular, the origin of the correlations is associated with fluctuations of channel mass density. The long-term memory effect, as measured by Hurst R/S analysis of experimental single-channel patch-clamp recordings, is close to the behaviour predicted by our models. The flexibility of the models enables their use as templates for other types of ion channel.

Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of $K^{+}$ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. One of the recent trends in molecular pharmacology is the evaluation of the therapeutic potential of natural compounds and their derivatives, which can exhibit high specificity and effectiveness. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health. Here, we focus on presenting the current state of knowledge about the possibilities of modulation of particular types of potassium channels by different flavonoids. Additionally, the biological meaning of the flavonoid-mediated changes in the activity of $K^{+}$ channels will be outlined. Finally, novel promising directions for further research in this area will be proposed.

Potassium channels play an important physiological role in glioma cells. In particular, voltage- and Ca2+-activated large-conductance BK channels (gBK in gliomas) are involved in intensive growth and extensive migrating behavior of the mentioned tumor cells, thus, they may be considered as a drug target in therapeutic treatment of glioblastoma. To enable appropriate drug design, molecular mechanisms of gBK channel activation by diverse stimuli should be unraveled, as well as the way that the specific conformational states of the channel relates to its functional properties (conducting/non-conducting). There is an open debate about the actual mechanism of BK channel gating, including the question of how the channel proteins undergo a range of conformational transitions when they flicker between non-conducting (functionally closed) and conducting (open) states. The details of channel conformational diffusion ought to have its representation in the properties of the experimental signal which describes the ion channel activity. Non-linear methods of analysis of experimental non-stationary series can be useful for observing the changes in the number of channel substates available from a geometrical and energetic point of view at given external conditions. In this work we analyze whether multifractal properties of activity of glioblastoma BK channels depend on membrane potential, and which states, conducting or nonconducting, affect the total signal to the larger extent. In this aim we carried out patch-clamp experiments at different levels of membrane hyper- and depolarization. The obtained time series of single channel currents were analyzed by the use of the Multifractal Detrended Fluctuation Analysis (MFDFA) method in a standard form and incorporating focus-based multifractal (FMF) formalism. Thus, we show the applicability of a modified MFDFA technique in analysis of an experimental patch clamp time series. The obtained results suggest that membrane potential strongly affects conformational space of the gBK channel proteins and the considered process has non-linear multifractal characteristics. These properties are inherent features of analyzed signals due to the fact that main tendencies vanish after shuffling the data.