Search Results (3,650)

This paper intends to go through the medical history of a new syndrome, beginning from its incidental observation to the nowadays ongoing reports quickly approaching 7000 published papers. This large number makes it difficult for the researcher to correctly quote the previous significant published data, and the usual strategy is to copy and paste the last articles references. This review is mainly detailed historical research of the step-by-step journey mainly of the first three decades, with less attention to the ongoing and late scientific controversies that are indeed quoted. The new syndrome was early named “precordial early repolarization (PER) syndrome” but became popular after being renamed “Brugada syndrome” (BS). Nowadays it is classified as one of the “J wave syndromes” (JWSs). The main characteristic of this new entity was an unusual astonishing precordial coved ST segment elevation that gave rise since its first descriptions to two different pathophysiological theories, one organic and the second functional. The first theory ascribed the ST elevation to an unusual pattern of depolarization at the right ventricular outflow tract (RVOT), while the second favored an abnormal dynamic repolarization pattern. Both phenomena were sometimes linked to an ion channel genetic abnormality. In the following decades, many eminent scientists and also some excellent humble cardiologists made significant observations regarding epidemiology, laboratory, diagnostic techniques, genetic, clinical findings, histology, embryology, therapeutic approaches, and risk stratification. This rush “to be the first who” has created more confusion than certainty, and only in this last decade a more scientific and less emotional approach has led to a common acceptance of an underlying organic background that causes a strange conduction delay mainly at the epicardial level of the RVOT. “Next generation” cardiologists are in charge of further elucidating the genetic, the structural, and electrical pathophysiology, and the correct risk stratification needed to correctly identify the true patients who need a therapy and avoid unusual and dangerous treatments to healthy people with a benign strange ECG. Full article

Pharmacotherapy of neuropathic pain (NP) remains challenging due to its heterogeneous etiology, lack of objective diagnostic tools, and the limited efficacy of currently available treatments, including antidepressants, anticonvulsants, and local anesthetics. Therefore, the search for novel therapies with improved analgesic efficacy and reduced adverse effects is of growing importance. In this context, natural alkaloids have emerged as promising candidates, demonstrating analgesic potential in both diabetes-induced neuropathy and various experimental models of NP. This review outlines NP pathophysiology, emphasizing maladaptive changes within the somatosensory nervous system, including peripheral and central sensitization, as well as glial cell activation. Furthermore, it discusses the mechanisms through which alkaloids may modulate NP-related pathways, with particular focus on their interactions with ion channels, signaling pathways, inflammatory responses, and oxidative stress. A literature search was conducted using the Scopus, Google Scholar and PubMed databases for papers published between 2015 and 2026, using the keywords “alkaloids” and “neuropathic pain”, and focused on recent findings regarding the antinociceptive effects of berbamine, tetrandrine, fangchinoline, and sinomenine, and their derivatives. The analysis indicates that, despite promising preclinical evidence, further rigorous preclinical and clinical studies are necessary to fully assess their therapeutic potential in the treatment of NP. Full article

Contrastive learning-based models such as DrugCLIP have recently emerged as scalable tools for structure-based virtual screening by embedding protein structures and small molecules into a shared representation space. While these approaches demonstrate high throughput and competitive screening performance in ligand retrieval tasks, their ability to correctly identify biologically relevant ligand-binding pockets has not been systematically evaluated. Here, we construct a benchmarking dataset comprising 42 pharmacologically diverse human protein targets with experimentally validated drug-bound structures spanning multiple target families. Using this dataset, we evaluate the pocket recognition capability of DrugCLIP and compare its performance with a traditional structure-based workflow (Fpocket combined with ESSA) and a machine learning-based method (P2Rank). DrugCLIP shows robust performance for well-characterized target classes, including kinases (10/10) and nuclear receptors (5/5), but exhibits markedly reduced accuracy for ion channels (1/4), GPCRs (3/5), and transporters (3/5). Notably, pocket prediction accuracy does not strongly correlate with structural data availability, suggesting that intrinsic pocket characteristics rather than training data abundance primarily affect model performance. Across the benchmark, DrugCLIP achieves an overall success rate of 71% (95% CI: 56–83%), compared with 79% (95% CI: 64–88%) for Fpocket+ESSA, and 93% (95% CI: 81–98%) for P2Rank. McNemar’s test showed no significant difference between DrugCLIP and Fpocket+ESSA (p = 0.508), whereas P2Rank significantly outperformed DrugCLIP (p = 0.012). Together, these results provide a quantitative evaluation of pocket recognition by contrastive learning-based models and highlight key limitations of embedding-based approaches for pocket localization. Full article

Nowadays, there is a deep interest in developing more compact user facilities, and plasma technology is one of the most promising techniques, not only for acceleration modules, but also for what is ancillary to the delivery of radiation to users, such as free electron lasers. In this regard, significant efforts have been made to miniaturize diagnostic stations, detection devices, and transfer lines, e.g., based on active plasma lenses. However, conventional undulators are still too cumbersome and expensive to meet the requirements of compactness and sustainability. For the aforementioned reasons, advanced undulator concepts have aroused great interest in pushing the frontier beyond conventional, magnet-based undulators. In this regard, a promising, very compact alternative is the use of the betatron motion of electrons in an ion channel to emulate an undulator device. This paper reports a feasibility study aiming to develop plasma-based undulator devices at SPARC_LAB as the test facility of the EuPRAXIA@SPARC_LAB project. In particular, this work provides a systematic assessment of free-electron-laser amplification in a plasma ion-channel undulator under experimentally realistic beam parameters, delivering quantitative predictions for gain and radiation performance in this configuration. Full article

Pollution of rivers and large water bodies, including reservoirs, by wastewater from various sources is one of the most critical issues in the Donetsk region, requiring continuous monitoring and assessment of surface water quality. The research aims to assess the state of the Kalmius River under anthropogenic pressure, as well as to find correlations between the species composition, photosynthetic activity of phytoplankton, and the degree of water pollution. This study presents the results of biomonitoring of the Kalmius River and its tributaries within Donetsk City, which are under intense anthropogenic pressure. Pollution of the river channel by phenol, anionic surfactants, Ferrum ions, chlorides, and sulfates was identified. Based on the combinatorial pollution index, the water in the Kalmius River and its tributaries can be classified as polluted. The pigment composition of water samples was analyzed, and the species composition of river phytoplankton was determined. Dominant species include Chlorella vulgaris Beij., Dictyosphaerium pulchellum H.C.Wood, Scenedesmus quadricauda Brébisson, and Oscillatoria agardhii M.A.Gomont. Photosynthetic activity of the river’s algal flora was assessed based on chlorophyll fluorescence induction curves of natural phytoplankton. A correlation was established between surface water pollution levels and changes in the photosynthetic apparatus of microalgae cells. A strong negative correlation was found between the content of nitrate nitrogen in the aquatic environment and the photosynthetic activity, pigment composition, and abundance of the main dominant forms of phytoplankton, particularly the microalgae of the genus Cyclotella. The data obtained shows that the Kalmius River’s pollution has a significant impact on phytoplankton biodiversity, leading to the growth of cyanobacteria species. Full article

(1) Background: Clinopodium pulchellum (Kunth) Govaerts (Panizara) is an aromatic Andean medicinal plant traditionally used in Peru to manage nervous disorders, insomnia, and digestive complaints; however, its neuropharmacological properties remain poorly validated. This study aimed to evaluate the anxiolytic- and antidepressant-like effects of C. pulchellum and to characterize its phytochemical profile as supportive evidence. (2) Methods: The essential oil was obtained by hydrodistillation and analyzed using GC–MS and GC–FID. (3) Results: Fifteen volatile compounds were identified based on retention indices and mass spectral data, with β-caryophyllene (22.9%) and linalool (19.1%) as the most representative constituents, while other compounds were tentatively identified. The aqueous extract showed total phenolic and flavonoid contents of 34.15 mg GAE/g and 29.44 mg QE/g, respectively, and moderate antioxidant activity (DPPH = 2.36 mg TE/g; ABTS = 3.33 mg TE/g). In vivo assays revealed that EOCP at 200 mg·kg⁻¹ significantly increased open-arm exploration in the elevated plus maze and reduced immobility time in the CUMS–forced swim test by 37% compared with the stress group, although the effect was lower than that of reference drugs. Molecular docking analysis indicated favorable binding affinities of β-caryophyllene, humulene, and aromandendrene with serotonergic and ion channel targets, while ADMET predictions suggested suitable pharmacokinetic properties. (4) Conclusions: These findings indicate that the observed neuropharmacological effects may be associated with the presence of bioactive terpenoids typical of Lamiaceae, supporting the traditional use of C. pulchellum. However, further studies are required to confirm the identity of uncommon constituents and to elucidate the mechanisms underlying its biological activity. Full article

A quantum model describing ion channels from an information-theoretic perspective is considered. The information $\chi$-capacity of an ion channel, treated as an information channel whose properties are modified by continuous quantum measurements, is investigated. The behavior of the $\chi$-capacity is analyzed as a function of the measurement parameters, in particular the type of measured observable, the measurement duration, and the measurement strength. It is shown that the information $\chi$-capacity exhibits qualitatively different behaviors depending on the measurement conditions, including regimes of rapid decay as well as regimes where it remains finite for long observation times. These results indicate that, within the considered model, continuous observation may significantly influence the information-theoretic properties of the effective ion-channel dynamics. Full article

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, including T-wave flattening, inversion, and biphasic T waves, which are also observed clinically. Loss of HDAC3 deacetylase activity, without affecting HDAC3 protein levels, was sufficient to induce QT prolongation. Disruption of HDAC3 function altered the expression of ion channel genes, including the downregulation of potassium channel genes such as Kcnh2, Kcne1, and Kcnip2. Moreover, a single dose of HDAC inhibitors, romidepsin or mocetinostat, caused reversible QT prolongation in mice. Consistent with these findings, HDAC inhibitor treatment altered the expression of potassium channel genes, with a predominant downregulation of multiple Kcn family members, including Kcnq1, Kcnh2, and Kcnip2. These findings establish HDAC3 enzymatic activity as a key regulator of cardiac repolarization and provide mechanistic insight into HDAC inhibitor-associated cardiotoxicity. Full article

Magnetic resonance techniques have evolved beyond conventional proton-based imaging, enabling access to a broader range of nuclei that provide complementary structural, functional, and molecular information. This review presents a comprehensive overview of multinuclear NMR and MRI in solid and soft materials as well as in biomedical applications, with particular emphasis on ¹H, ¹³C, ³¹P, ²³Na, and ¹⁹F nuclei. Proton-based methods remain the foundation of magnetic resonance due to their high sensitivity and widespread applicability, offering insights into molecular mobility, hydration, and microstructural heterogeneity. In contrast, heteronuclear approaches enable more specific characterization of chemical structure (¹³C), phosphorus-containing functional groups and membranes (³¹P), ionic homeostasis and transport (²³Na), and exogenous tracers with negligible biological background (¹⁹F). Together, these techniques extend magnetic resonance from primarily anatomical imaging toward functional, metabolic, and molecular-level analysis. The review further discusses key hardware aspects, including magnetic field strength and radiofrequency coil design, highlighting the trade-offs between low- and high-field systems and the growing importance of multinuclear coil architectures. For example, because ¹H, ²³Na, ³¹P, and ¹⁹F resonate at different Larmor frequencies, multinuclear experiments require dedicated or multi-tuned RF coils that balance sensitivity, field homogeneity, and decoupling between channels. Mechanisms of contrast generation are examined in detail, distinguishing between endogenous sources—such as water, ions, and metabolites—and exogenous contrast agents, including gadolinium-, manganese-, and fluorine-based compounds, as well as targeted and theranostic platforms. A comparative framework of endogenous and exogenous signals is presented, emphasizing their complementary roles in balancing safety, specificity, and sensitivity. Finally, the opportunities and challenges of multinuclear magnetic resonance are critically evaluated, including limitations in sensitivity, signal-to-noise ratio, data interpretation in heterogeneous systems, and technical complexity. Emerging directions such as ultrahigh-field imaging, advanced RF technologies, hyperpolarization, and artificial intelligence-assisted reconstruction are discussed as key drivers for future development. Overall, multinuclear NMR and MRI represent a powerful and expanding toolbox for probing complex material and biological systems, with the potential to significantly enhance diagnostic capabilities and deepen our understanding of structure–function relationships across multiple scales. Full article

Ferroptosis is an iron-dependent, lipid peroxidation–driven form of regulated cell death that has emerged as a therapeutic vulnerability in hepatocellular carcinoma (HCC), yet the contribution of lysosomes to this process remains incompletely understood. In this study, we investigated whether lysosomal ion channels regulate ferroptosis sensitivity in HCC cells, focusing on the two-pore channel 2 (TPC2) and the transient receptor potential mucolipin 1 (TRPML1). Using pharmacological modulation, genetic knockout models, flow cytometry-based cell death and lipid peroxidation assays, lipidomics, calcium measurements, and molecular analyses across multiple HCC cell lines, we examined how these channels influence ferroptotic signaling. We show that NAADP-dependent TPC2 activity is required for efficient ferroptosis induction, whereas TPC2 loss renders HCC cells resistant to ferroptosis triggered by system Xc⁻ inhibition or glutathione peroxidase 4 (GPX4)blockade. This resistance is associated with reduced lipid peroxidation, altered calcium signaling, and selective depletion of polyunsaturated phosphatidylethanolamine species linked to decreased Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) expression. In contrast, TRPML1 deficiency sensitizes cells to ferroptosis and correlates with enhanced endoplasmic reticulum stress and oxidative imbalance rather than major lipid remodeling. Collectively, these findings identify lysosomal ion channels as key modulators of ferroptosis in HCC and highlight distinct mechanisms by which TPC2 and TRPML1 regulate cellular redox balance and death susceptibility. Full article

During production, fish are exposed to multiple environmental, physiological, and physical stressors, which compromise development, productivity, and welfare and urge the implementation of effective and safe stress-mitigating strategies, particularly during early developmental stages. Larval zebrafish (Danio rerio) constitute a powerful model for studying acute stress responses due to the numerous advantages they offer, such as developmental transparency, a conserved hypothalamic–pituitary–interrenal (HPI) axis, and suitability for high-throughput screening. This review examines the potential of natural monoterpenes as stress-reducing compounds and compares their performance with conventional synthetic anesthetics. Evidence from vortex-flow stress paradigms, behavioral profiling and biochemical assays shows that acute stress in zebrafish larvae triggers metabolic disruption, behavioral hyperactivity and enzyme imbalance, with cortisol responses depending on stimulus intensity. Monoterpenes such as thymol and menthol consistently reduce stress-induced hyperactivity, support redox homeostasis and display favorable safety profiles at low doses and short exposures. Nevertheless, as research into these substances is still recent, evidence of any potential adverse effects is still limited. Although individual monoterpenes may act on different subsets of molecular targets, their multimodal mechanisms, including gamma-aminobutyric acid (GABA)ergic enhancement, voltage-gated ion channel and transient receptor potential (TRP) modulation, suggest broader and potentially safer actions compared to single-target anesthetics as tricaine methane sulfonate (MS-222). Collectively, these findings suggest that monoterpenes offer promising natural alternatives for stress mitigation in aquaculture and the refinement of research procedures involving early life stages. Full article

Insect odorant receptors (ORs) are pivotal molecular interfaces that translate environmental chemical cues into neuronal electrical impulses, thereby governing essential behaviors such as foraging, mating, oviposition, and predator avoidance. The past three years have witnessed a paradigm shift driven by high-resolution cryo-electron microscopy (cryo–EM) structures of OR-odorant receptor co-receptor (Orco) heterocomplexes, which definitively established the 1:3 stoichiometry (one odorant-specific OR subunit and three Orco subunits) of the functional ion channel. These structures have revealed the architecture of the ligand-binding pocket and the conformational dynamics underlying channel gating. This structural framework has illuminated long-standing questions regarding the evolution of ORs from ancestral gustatory receptors and their lineage-specific expansion via a “birth-and-death” model, enabling adaptation to diverse ecological niches. Concurrently, the long-debated signal transduction mechanism has been reconciled by evidence of a unified bimodal system, where OR–Orco complexes function as both direct ligand-gated ion channels and activators of an IP3-dependent metabotropic cascade. Here, we integrate these recent breakthroughs—from atomic-level structures and evolutionary genomics to in vivo functional validation—with classical knowledge of OR expression, localization, and diversity. We further synthesize the emerging field of structure-guided applications, including virtual screening for novel semiochemicals and the development of RNAi- and CRISPR-based strategies for pest management. This comprehensive review provides a framework for understanding the molecular logic of insect olfaction and its exploitation for biotechnological innovation. Full article

Micro- and nanoplastics (MNPs) are ubiquitous environmental pollutants recognized as emerging and relevant risk factors for numerous human diseases, including cardiovascular diseases. MNPs enter the human body through ingestion, inhalation, and dermal penetration, and their toxicity varies according to size, shape, and chemical composition, most notably between microplastics (>1 µm) and nanoplastics (<1 µm), which differ in cellular uptake mechanisms and biodistribution. Recent evidence has confirmed their presence in cardiac and vascular tissues, raising significant concerns about their potential impact on human health. This review summarizes current knowledge on MNP exposure sources, physicochemical properties, and systemic bioavailability, with a particular emphasis on the mechanisms of transport that facilitate their deposition within the myocardium and vasculature. It further addresses a broad spectrum of cardiotoxic effects, including oxidative stress, mitochondrial injury, immune activation, ion channel disruption, cell death, and fibrosis. Endothelial dysfunction, vascular injury, and pro-atherogenic activity are also discussed. In addition to outlining existing detection techniques and emerging in vitro models, the review highlights initial steps toward the development of preventive strategies. Concluding with key knowledge gaps and future research directions, this article underscores the urgent need for standardized measurement tools, deeper insights into damage mechanisms, and clinical interventions to prevent MNP-induced cardiovascular diseases. Full article

The continuously improving power density of Li-ion batteries and the widespread application of fast charging and discharging have rendered thermal management an increasingly critical task. Cold plates are among the most important means for such a task, and their channel structure significantly affects battery performance. Aiming to further improve the thermohydraulic performance of cold plate, this study proposes a cold plate with sinusoidal wave-shaped channel. Using channel quantity, amplitude, wavelength, diameter, and coolant mass flow rate as variables, the orthogonal experimental scheme is employed to design combinations of different variables for numerical simulation. The numerical simulation results are used to train a deep neural network for cold plate performance prediction. The trained neural network can accurately predict the maximum temperature, comprehensive performance indicators, and entropy generation rate with errors below 5.0%, 5.0%, and 10.0%, respectively. Multi-objective optimization design (MOOD) is implemented by combining a deep neural network with the NSGA-II genetic optimization, yielding two sets of Pareto fronts as follows: one for maximizing comprehensive performance indicator and minimizing entropy generation rate, and the other for minimizing maximum temperature and entropy generation rate, and TOPSIS decision points are provided. This study provides a new method and valuable MOOD results for the thermal management of Li-ion batteries and cold plate engineering while offering theoretical guidance for practical applications. Full article

Neuronal excitability manifests itself mainly in the form of non-linear, self-regenerative waves of electricity moving along the surface of neuronal axons. These waves are commonly known as action potentials (APs). Theoretical and experimental investigations of the physical and functional characteristics of APs have broadly followed along the lines of the ionic hypothesis and the associated mathematical model introduced by Hodgkin and Huxley (HH). In the current form of this bioelectrical framework, adopted in mainstream physiology and other biological sciences, the axonal membrane is conceptualized as an electronic circuit where electric current is generated and propelled as a result of the time-dependent opening and closure of voltage-operated ion channel proteins, allowing passive flow of specific ions across and along the membrane, powered by their respective electrochemical gradients. Although representing mainstream research, the bioelectric perspective has been criticized for its narrow focus on the electrical characteristics of APs, whilst ignoring other physical manifestations of the nerve signal, particularly mechanical and thermal changes coinciding with AP propagation. As an alternative, a macroscopic thermodynamics-based acoustic theory has been outlined, in which all electric and non-electric manifestations of the nerve signal are considered as a result of a single density pulse in the axonal membrane carried by a reversible lipid membrane phase transition and momentum conservation. Representing a minority view, however, this unified, acoustic perspective on the physical nature of neuronal excitability is largely ignored by representatives of the bioelectric perspective. Here, we draw special attention to the philosophical dimension of the communication failure between the two communities of scientists. We argue that adherents of the bioelectric perspective favor a mechanist type of explanation, whilst supporters of the acoustic perspective are committed to so-called covering-law types of explanation. We conclude that it is this thus far unrecognized philosophical rift, rather than specific scientific differences in opinion, that blocks fruitful interdisciplinary cooperation necessary for building a comprehensive, fully integrated notion of the physical nature of neuronal excitability. Suggestions of how to bridge this conceptual gap are formulated. Full article