Prophylaxis by a reversible cholinesterase inhibitor and the treatment NMDA receptor antagonists as combinatorial countermeasure against nerve agent poisoning in mice model.

The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed.

Coexisting Phases of Individual VO Nanoparticles for Multilevel Nanoscale Memory.

Vanadium dioxide (VO) has received significant interest in the context of nanophotonic metamaterials and memories owing to its reversible insulator-metal transition associated with significant changes in its optical and electronic properties. The phase transition of VO has been extensively studied for several decades, and the ways how to control its hysteresis characteristics relevant for memory applications have significantly improved. However, the hysteresis dynamics and stability of coexisting phases during the transition have not been studied on the level of individual single-crystal VO nanoparticles (NPs), although they represent the fundamental component of ordinary polycrystalline films and can also act like nanoscale memory units on their own.

Dizocilpine derivatives as neuroprotective NMDA receptor antagonists without psychomimetic side effects.

We aimed to prepare novel dibenzo [a,d][7]annulen derivatives that act on N-methyl-d-aspartate (NMDA) receptors with potential neuroprotective effects. Our approach involved modifying the tropane moiety of MK-801, a potent open-channel blocker known for its psychomimetic side effects, by introducing a seven-membered ring with substituted base moieties specifically to alleviate these undesirable effects. Our in silico analyses showed that these derivatives should have high gastrointestinal absorption and cross the blood-brain barrier (BBB).

Influence of Deposition Parameters on the Plasmonic Properties of Gold Nanoantennas Fabricated by Focused Ion Beam Lithography.

The behavior of plasmonic antennas is influenced by a variety of factors, including their size, shape, and material. Even minor changes in the deposition parameters during the thin film preparation process may have a significant impact on the dielectric function of the film, and thus on the plasmonic properties of the resulting antenna. In this work, we deposited gold thin films with thicknesses of 20, 30, and 40 nm at various deposition rates using an ion-beam-assisted deposition.

Analytical electron microscopy analysis of insulating and metallic phases in nanostructured vanadium dioxide.

Vanadium dioxide (VO) is a strongly correlated material that exhibits the insulator-to-metal transition (IMT) near room temperature, which makes it a promising candidate for applications in nanophotonics or optoelectronics. However, creating VO nanostructures with the desired functionality can be challenging due to microscopic inhomogeneities that can significantly impact the local optical and electronic properties. Thin lamellas, produced by focused ion beam milling from a homogeneous layer, provide a useful prototype for studying VO at the truly microscopic level using a scanning transmission electron microscope (STEM).

MXenes with ordered triatomic-layer borate polyanion terminations.

Surface terminations profoundly influence the intrinsic properties of MXenes, but existing terminations are limited to monoatomic layers or simple groups, showing disordered arrangements and inferior stability. Here we present the synthesis of MXenes with triatomic-layer borate polyanion terminations (OBO terminations) through a flux-assisted eutectic molten etching approach. During the synthesis, Lewis acidic salts act as the etching agent to obtain the MXene backbone, while borax generates BO species, which cap the MXene surface with an O-B-O configuration.

Pro-cognitive effects of dual tacrine derivatives acting as cholinesterase inhibitors and NMDA receptor antagonists.

Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors.

mTOR pathway inhibition alters proliferation as well as differentiation of neural stem cells.

Introduction: Neural stem cells (NSCs) are essential for both embryonic development and adult neurogenesis, and their dysregulation causes a number of neurodevelopmental disorders, such as epilepsy and autism spectrum disorders. NSC proliferation and differentiation in the developing brain is a complex process controlled by various intrinsic and extrinsic stimuli. The mammalian target of rapamycin (mTOR) regulates proliferation and differentiation, among other cellular functions, and disruption in the mTOR pathway can lead to severe nervous system development deficits.

Analysis of Surface Expression of NMDAR Subunits in Primary Hippocampal Neurons.

The expression and activity of ionotropic glutamate receptors control signal transduction at the excitatory synapses in the CNS. The NMDAR comprises two obligatory GluN1 subunits and two GluN2 or GluN3 subunits in different combinations. Each GluN subunit consists of four domains: the extracellular amino-terminal and agonist-binding domains, the transmembrane domain, and the intracellular C-terminal domain (CTD).

Plasmonic sensing using Babinet's principle.

Developing methods to sense local variations in properties of nearby materials, such as their refractive index and thickness, are important in numerous fields including chemistry and biomedical applications. Localized surface plasmons (LSPs) excited in plasmonic nanostructures have been demonstrated to be useful in this context due to the spectral location of their associated resonances being sensitive to changes in the environment near the plasmonic structures. This manuscript explores Babinet's principle by exploiting LSP resonances excited in complementary metal-dielectric cylindrical plasmonic structures (plasmonic particle-dimers and aperture-dimers in our case).

2D calculation of parasitic fields in misaligned multipole electron-optical systems.

The effects of geometrical imperfections in electron-optical components are usually evaluated in 3D simulations. These calculations inherently take a long time, require a large amount of memory, and do not directly produce the necessary axial field functions. We present a 2D perturbation method to calculate parasitic fields in misaligned multipole systems.

Correlative Imaging of Individual CsPbBr Nanocrystals: Role of Isolated Grains in Photoluminescence of Perovskite Polycrystalline Thin Films.

We report on the optical properties of a CsPbBr polycrystalline thin film on a single grain level. A sample composed of isolated nanocrystals (NCs) mimicking the properties of the polycrystalline thin film grains that can be individually probed by photoluminescence spectroscopy was prepared. These NCs were analyzed using correlative microscopy allowing the examination of structural, chemical, and optical properties from identical sites.

Spatio-spectral metrics in electron energy loss spectroscopy as a tool to resolve nearly degenerate plasmon modes in dimer plasmonic antennas.

Electron energy loss spectroscopy (EELS) is often utilized to characterize localized surface plasmon modes supported by plasmonic antennas. However, the spectral resolution of this technique is only mediocre, and it can be rather difficult to resolve modes close in the energy, such as coupled modes of dimer antennas. Here, we address this issue for a case study of the dimer plasmonic antenna composed of two gold discs.

Structure-Guided Design of -Methylpropargylamino-Quinazoline Derivatives as Multipotent Agents for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex disease with an unknown etiology. Available treatments, limited to cholinesterase inhibitors and -methyl-d-aspartate receptor (NMDAR) antagonists, provide symptomatic relief only. As single-target therapies have not proven effective, rational specific-targeted combination into a single molecule represents a more promising approach for treating AD, and is expected to yield greater benefits in alleviating symptoms and slowing disease progression.

Subunit-Dependent Surface Mobility and Localization of NMDA Receptors in Hippocampal Neurons Measured Using Nanobody Probes.

NMDA receptors (NMDARs) are ionotropic glutamate receptors that play a key role in excitatory neurotransmission. The number and subtype of surface NMDARs are regulated at several levels, including their externalization, internalization, and lateral diffusion between the synaptic and extrasynaptic regions. Here, we used novel anti-GFP (green fluorescent protein) nanobodies conjugated to either the smallest commercially available quantum dot 525 (QD525) or the several nanometer larger (and thus brighter) QD605 (referred to as nanoGFP-QD525 and nanoGFP-QD605, respectively).

Typology of Users of Psychedelics and Alike Psychoactive Substances in Czechia: Results of the National Online Survey.

The aim of this study was to define the typical groups of users of psychedelics and alike psychoactive substances in Czechia regarding various variables such as demographics, their patterns of use, or motivation for use. Data from 890 Czech respondents were collected through an online questionnaire as a part of The National Psychedelic Research Project. Subjects reported experience with the use of 29 selected substances by answering 133 questions of the questionnaire.

Acetabular fracture after cycling related falls: High index of suspicion is required to avoid missing the injury on plain radiographs.

Cycling participation as a medium of transport and as a competitive sport has steadily increased in recent decades. Traumatic injuries secondary to falls and collisions occur relatively frequently. Fractures of the hip and pelvis are uncommon with no studies to date reporting their exact incidence in this sport.

Increased alcohol dehydrogenase 1 activity promotes longevity.

Several molecules can extend healthspan and lifespan across organisms. However, most are upstream signaling hubs or transcription factors orchestrating complex anti-aging programs. Therefore, these molecules point to but do not reveal the fundamental mechanisms driving longevity.

Plasmonic Properties of Individual Gallium Nanoparticles.

Gallium is a plasmonic material offering ultraviolet to near-infrared tunability, facile and scalable preparation, and good stability of nanoparticles. In this work, we experimentally demonstrate the link between the shape and size of individual gallium nanoparticles and their optical properties. To this end, we utilize scanning transmission electron microscopy combined with electron energy loss spectroscopy.

The pathogenic N650K variant in the GluN1 subunit regulates the trafficking, conductance, and pharmacological properties of NMDA receptors.

N-methyl-D-aspartate receptors (NMDARs) play an essential role in excitatory neurotransmission in the mammalian brain, and their physiological importance is underscored by the large number of pathogenic mutations that have been identified in the receptor's GluN subunits and associated with a wide range of diseases and disorders. Here, we characterized the functional and pharmacological effects of the pathogenic N650K variant in the GluN1 subunit, which is associated with developmental delay and seizures. Our microscopy experiments showed that when expressed in HEK293 cells (from ATCC®), the GluN1-N650K subunit increases the surface expression of both GluN1/GluN2A and GluN1/GluN2B receptors, but not GluN1/GluN3A receptors, consistent with increased surface expression of the GluN1-N650K subunit expressed in hippocampal neurons (from embryonic day 18 of Wistar rats of both sexes).