Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling.

The search for novel effective TAAR1 ligands continues to draw great attention due to the wide range of pharmacological applications related to TAAR1 targeting. Herein, molecular docking studies of known TAAR1 ligands, characterized by an oxazoline core, have been performed in order to identify novel promising chemo-types for the discovery of more active TAAR1 agonists. In particular, the oxazoline-based compound has been taken as a reference compound for the computational study, leading to the development of quite flat and conformationally locked ligands.

Spectrum of Surgical Site Infection Pathogens in Chronic Infectious Spondylitis Requiring Revision Surgery: A 5-Year Cohort Study.

Spectrum monitoring of the pathogen in spondylitis patients plays a key role in preventing infectious complications of spinal reconstructions in chronic spondylitis (CS) and in the treatment of surgical site infection (SSI). The aim of this study is to characterize the spectrum of SSI pathogens in CS requiring revision surgery. The primary cohort encompassed 569 surgical patients with infectious CS.

Bioorthogonal chemistry of polyoxometalates - challenges and prospects.

Bioorthogonal chemistry has enabled scientists to carry out controlled chemical processes in high yields while minimizing hazardous effects. Its extension to the field of polyoxometalates (POMs) could open up new possibilities and new applications in molecular electronics, sensing and catalysis, including inside living cells. However, this comes with many challenges that need to be addressed to effectively implement and exploit bioorthogonal reactions in the chemistry of POMs.

Phosphorescent Cyclometalated Palladium(II) and Platinum(II) Complexes Derived from Diaminocarbene Precursors.

Metal-mediated self-assembly of isocyanides and methyl 4-aminopyrimidine-5-carboxylate leads to luminescent Pd and Pt complexes featuring C,N-cyclometalated acyclic diaminocarbene (ADC) ligands. The solid-state luminescent properties of these diaminocarbene derivatives are attributed to their triplet-state metal/metal-to-ligand charge-transfer (MMLCT) nature, which is driven by attractive intermolecular M···M interactions further reinforced by the intramolecular π-π interactions even in the structure of the Pd compound, which is the first Pd-ADC phosphor reported.

RNA-seq analysis of parasitism by Intoshia linei (Orthonectida) reveals protein effectors of defence, communication, feeding and growth.

Orthonectida is a group of multicellular endoparasites of a wide range of marine invertebrates. Their parasitic stage is a multinuclear shapeless plasmodium infiltrating host tissues. The development of the following worm-like sexual generation takes place within the cytoplasm of the plasmodium.

The Aha! experience is associated with a drop in the perceived difficulty of the problem.

The study investigated the correlation between the intensity of the Aha! experience and participants' subjective difficulty ratings of problems before and after finding their solutions. We assumed that the Aha! experience arises from a shift in processing fluency triggered by changing from an initially incoherent problem representation to a coherent one, which ultimately leads to the retrieval of a solution with unexpected ease and speed. First, we hypothesized that higher Aha! experience ratings would indicate more sudden solutions, manifesting in a reduced correlation between the initial difficulty ratings and solution times.

Fossil mosses are emitting methane after maritime Antarctic glacier retreat.

In the extraordinary weather conditions of the austral summer of 2023, fossil mosses thawed out from under the Bellingshausen Ice Dome, King George Island, Southern Shetland Archipelago of maritime Antarctica. At the end of the austral summer, we directly measured greenhouse gas fluxes (CH and CO) from the surface of fossil mosses. We showed that fossil mosses were strong emitters of CH and weak emitters of CO.

Design of luminescent complexes with different CuI cores based on pyridyl phenoxarsines.

A series of luminescent CuI clusters with stair-step, cubane, and octahedral geometries supported by a novel type of cyclic As,N-ligand, pyridyl-containing 10-phenoxarsines, were synthesized and characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction analysis. An unusual arrangement of As,N-bidentate and μ-iodo ligands was found in the octahedral cluster. The structural diversity of the Cu(I) complexes is reflected in their photophysical properties: the phosphorescence spectra of the compounds display emission in a broad spectral range of 495-597 nm.

Mutual Placement of Isocyanide and Phosphine Ligands in Platinum(II) Complexes [PtHalLL] (Hal = Cl, Br, I; L,L = CNCy, PPh) Leads to Highly-Efficient Photocatalysts for Hydrosilylation of Alkynes.

A series of platinum complexes featuring phosphine and isocyanide ligands [PtX(PPh)(CNCy)] (X = Cl, Br, and I) as well as their parent phosphine [PtX(PPh)] and isocyanide [PtX(CNCy)] analogues have been prepared and evaluated as catalysts for the photocatalytic hydrosilylation of alkynes. Under violet light irradiation (λ = 400 nm), phosphine-isocyanides complexes [PtX(PPh)(CNCy)] gave high yields of silylated products (product yield up to 99%, TONs up to 1.98 × 10).

Simultaneous Catechol and Hydroquinone Detection with Laser Fabricated MOF-Derived Cu-CuO@C Composite Electrochemical Sensor.

The conversion of metal-organic frameworks (MOFs) into advanced functional materials offers a promising route for producing unique nanomaterials. MOF-derived systems have the potential to overcome the drawbacks of MOFs, such as low electrical conductivity and poor structural stability, which have hindered their real-world applications in certain cases. In this study, laser scribing was used for pyrolysis of a Cu-based MOF ([Cu{1,4-CH(COO)}(4,4'-bipy)]) to synthesize a Cu-CuO@C composite on the surface of a screen-printed electrode (SPE).

Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays.

Trace amine-associated receptor 1 (TAAR1) is an attractive target for the design of innovative drugs to be applied in diverse pharmacological settings. Due to a non-negligible structural similarity with endogenous ligands, most of the agonists developed so far resulted in being affected by a low selectivity for TAAR1 with respect to other monoaminergic G protein-coupled receptors, like the adrenoreceptors. This study utilized comparative molecular docking studies and quantitative-structure activity relationship (QSAR) analyses to unveil key structural differences between TAAR1 and alpha2-adrenoreceptor (α-ADR), with the aim to design novel TAAR1 agonists characterized by a higher selectivity profile and reduced off-target effects.

Alterations in Serotonin Neurotransmission in Hyperdopaminergic Rats Lacking the Dopamine Transporter.

Biogenic amines dopamine (DA) and serotonin (5-HT) are among the most significant monoaminergic neurotransmitters in the central nervous system (CNS). Separately, the physiological roles of DA and 5-HT have been studied in detail, and progress has been made in understanding their roles in normal and various pathological conditions (Parkinson's disease, schizophrenia, addiction, depression, etc.).

Linkage of the Dinuclear Gold(I) Complex Luminescence and Origin of Endocyclic Amino Group of Cyclic PN-Bridging Ligands.

Gold(I) complexes of LAuCl composition based on PN ligands, namely 1,5-diaza-3,7-diphosphacyclooctanes, containing ethylpyridyl substituents at the phosphorus atoms and sp- or sp-hybridized endocyclic nitrogen atoms were synthesized. The SCXRD analysis indicated the strong impact of the geometry of the nitrogen atom on the structure and conformational flexibility of the complexes. The -aryl substituted ligand with the planar endocyclic nitrogen atom provides higher flexibility of the complex and an ability to bind the solvent molecules in the "host-guest" mode, whereas that kind of behavior is forbidden for the complex with an -alkyl substituted ligand with a pyramidal nitrogen atom.

Two new species of the genus Leptomyxa (Goodey, 1915) - Leptomyxa botanica n. sp. and Leptomyxa monrepos n. sp. from the soil habitats of Northwestern Russia.

Amoebae of the genus Leptomyxa have variable morphologies and can only be reliably identified using molecular data. However, species distinction based on the 18S rRNA gene sequence is difficult due to the very low level of sequence divergence among morphologically different species. The database for other genes is much smaller, and genomic data on Leptomyxa is almost absent.

Exploration of differentiability in a proton computed tomography simulation framework.

Gradient-based optimization using algorithmic derivatives can be a useful technique to improve engineering designs with respect to a computer-implemented objective function. Likewise, uncertainty quantification through computer simulations can be carried out by means of derivatives of the computer simulation. However, the effectiveness of these techniques depends on how 'well-linearizable' the software is.

To the Origin of Fungi: Analysis of MFS Transporters of First Assembled Genome Highlights Dissimilarity of Osmotrophic Abilities between Aphelida and Fungi.

Aphelids are a holomycotan group, represented exclusively by parasitoids infecting algae. They form a sister lineage to Fungi in the phylogenetic tree and represent a key group for reconstruction of the evolution of Holomycota and for analysis of the origin of Fungi. The newly assembled genome of (Holomycota, Aphelida) with a total length of 18.

Alkynylphosphonium Pt(II) Complexes: Synthesis, Characterization, and Features of Photophysical Properties in Solution and in the Solid State.

A series of heteroleptic bis-alkynyl-diimine mononuclear Pt(II) complexes with alkynylphosphonium and di--butyl-2,2'-bipyridine (dtbpy) ligands have been prepared and characterized by spectroscopic methods and single-crystal XRD. The Pt(II) complexes obtained in the present study demonstrate triplet emission in solution, which originates from MLCT/LC states where the nature of the π-conjugated linker in the alkynylphosphonium ligand manages the contributions of each transition, and this conclusion is supported by DFT calculations. Additionally, the presence of the phosphonium group connected to alkynyl through the π-conjugated linker enhances nonlinear optical properties of the Pt(II) complexes increasing two-photon absorption cross section up to 400 GM.

X/Y platinum(II) complexes: some features of supramolecular assembly halogen bonding.

Four series of new luminescent cyclometalated complexes [Pt(C^N)(IPy)Y] (HC^N = 2-phenylpyridine (Hppy), 2-(1-benzofuran-3-yl)pyridine (Hbfpy), methyl-2-phenylquinoline-4-carboxylate (Hmpqc), 2-(1-benzothiophen-3-yl)pyridine (Hbtpy), IPy = 4-iodopyridine, and Y = Cl, Br, I) have been investigated as X/Y 'building blocks' for the construction of a supramolecular network utilizing the I atom in IPy as a halogen bond (XB) donor (the X atom). The σ-hole of the X atom was found to provide non-covalent X⋯Y, X⋯Pt and X⋯π (π system of the metalated chelate ring) interactions for the complexes in the crystal state. NBO analysis confirms donation of the platinum electron density to iodine upon the X⋯Pt interaction.

Integrated Smart Gas Tracking Device with Artificially Tailored Selectivity for Real-Time Monitoring Food Freshness.

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness via the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4 °C) and high humidity (90% R.

The Expression of Trace Amine-Associated Receptors (TAARs) in Breast Cancer Is Coincident with the Expression of Neuroactive Ligand-Receptor Systems and Depends on Tumor Intrinsic Subtype.

Currently, the contribution of trace amine-associated receptors (TAARs) to breast cancer (BC) is recognized, but their associations with various pathological characteristics are not yet understood. There is accumulated transcriptomic data for BC tumors, which are represented in publicly accessible databases. We estimated TAARs' (including TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) associations with BC stage, grade, and molecular subtypes in these data and identified that the expression of all TAARs was associated with more unfavorable cancer subtypes, including basal-like and HER2-positive tumors.

Uncertainty-aware spot rejection rate as quality metric for proton therapy using a digital tracking calorimeter.

Proton therapy is highly sensitive to range uncertainties due to the nature of the dose deposition of charged particles. To ensure treatment quality, range verification methods can be used to verify that the individual spots in a pencil beam scanning treatment fraction match the treatment plan. This study introduces a novel metric for proton therapy quality control based on uncertainties in range verification of individual spots.

Temporal Variability of Gallium in Natural Plants.

The aim of the research was to study the distribution of gallium (Ga) in rhizosphere soil and in plants growing under natural conditions in uncontaminated sites, with an emphasis on temporal fluctuations of Ga concentration in plants. For this purpose, two field experiments were conducted in St. Petersburg, Russia, in 2019 and 2020, at two sites.

Dopamine Transporter Knockout Rats Display Epigenetic Alterations in Response to Cocaine Exposure.

(1) Background: There is an urgent need for effective treatments for cocaine use disorder (CUD), and new pharmacological approaches targeting epigenetic mechanisms appear to be promising options for the treatment of this disease. Dopamine Transporter (DAT) transgenic rats recently have been proposed as a new animal model for studying susceptibility to CUD. (2) Methods: DAT transgenic rats were treated chronically with cocaine (10 mg/kg) for 8 days, and the expression of epigenetic modulators, Lysine Demethylase 6B (KDM6B) and Bromodomain-containing protein 4 (BRD4), was examined in the prefrontal cortex (PFC).

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency.

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study.

Increasing the redox switching capacity of Lindqvist-type hexavanadates by organogold post-functionalisation.

The covalent attachment of organogold(I) moieties to the Lindqvist-type polyoxovanadate results in a measurable charge re-distribution across the formed Au-{V6}-Au linkages. Scanning probe microscopy studies of these hybrid compounds on the Au(111) surface demonstrate the increase in the number of switching states with stepwise increase in molecular conductance, compared with unfunctionalised hexavanadates.