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关键词： Cocaine   Dopamine   Dopamine transporter   FSCV   Hypocretin   Motivation   Orexin  

摘要： Relapse to cocaine use after periods of abstinence remains a significant challenge for treating cocaine use disorder. While the neurobiological mechanisms underlying relapse are still under investigation, adaptations in mesolimbic dopamine systems may contribute to cocaine craving and propensity for relapse. Therefore, reversing or preventing these dopamine adaptations may reduce motivation for cocaine and decrease the likelihood of relapse. The hypocretin/orexin system has been shown repeatedly to regulate cocaine-associated behavior and dopamine transmission. For example, our previous studies indicated that the hypocretin receptor 1 antagonist—RTIOX-276—reduced behavioral and dopamine responses to cocaine. Importantly, the effects of RTIOX-276 on dopamine transmission persisted for at least 24 hr, suggesting lasting effects of hypocretin receptor antagonism. Here, we hypothesized that a single RTIOX-276 treatment early in abstinence would reduce motivation for cocaine and prevent alterations in dopamine transmission later in abstinence. Female and male rats were pre-assessed for cocaine consumption and motivation using a within-session threshold schedule before undergoing 7 days of intermittent access to cocaine. After intermittent access self-administration, rats were treated with RTIOX-276 on the first day of a 7-day abstinence period, after which they were reassessed for cocaine consumption and motivation or examined for dopamine transmission using fast-scan cyclic voltammetry in nucleus accumbens core slices. We found that a single treatment with RTIOX-276 on the first day of abstinence reduced motivation for cocaine and prevented aberrant dopamine uptake observed following intermittent access to cocaine. These findings suggest that hypocretin receptor 1 may be a viable target for reducing motivation for cocaine through alterations in dopamine transmission in the nucleus accumbens.

关键词： 2.2 ' -bipyridine   ESR   DFT   Antimicrobial   Antioxidant   Cytotoxicity  

摘要： Diethyl hydrazine-1,2-dicarboxylate (H₂DEC) and 2,2′-bipyridine (Bipy) were used to synthesize three mixed-ligand metal complexes:[Cu(HDEC)(Bipy)(H₂O)Cl₂]·H₂O, [Ni₂(H₂DEC)(Bipy)₂(H₂O)₂Cl₂].H₂O, and [Pd₂(DEC)(Bipy)₂].2Cl·2H₂O. The investigated complexes were characterized by a variety of methods, including FT-IR, UV–Vis., and ¹H NMR spectroscopy, mass spectrometry, X-ray diffraction (both single-crystal and powder), cyclic voltammetry, ESR, magnetic susceptibility measurements, and thermogravimetric analysis (TGA). We calculated the kinetic and thermodynamic parameters by applying the Coats–Redfern and Horowitz–Metzger methods. Structural analysis indicated that the Cu(II) and Ni(II) complexes exhibit octahedral geometries, whereas the Pd(II) complex adopts square planner geometry. Photoluminescence measurements showed two broad emission bands at 535 nm and 565 nm for [Cu(HDEC)(Bipy)(H₂O)Cl₂].H₂O, and a single band at 535 nm for [Ni₂(H₂DEC)(Bipy)₂(H₂O)₂Cl₂]H₂O. The anticipated structures were also confirmed by DFT-based geometric optimization. Biological screening revealed that the Ni(II) and Cu(II) complexes displayed moderate cytotoxic activity , with IC₅₀ values of 28.5 and 61 μM, respectively against HeLa cell lines. Among the synthesized complexes, [Cu(HDEC)(Bipy)(H₂O)Cl₂]H₂O exhibited the highest antioxidant activity, achieving 96.03% and 59.61% radical scavenging in the ABTS and DPPH assays, respectively.

关键词： LaAlO3   Perovskite   Lanthanum aluminate   DFT   First principles   Ethanol   C2H5OH  

摘要： Ethanol adsorption on the LaO-terminated LaAlO₃ (0 0 1) surface at low coverage was investigated using Density Functional Theory (DFT) with van der Waals (vdW) corrections. The most stable configuration involves ethanol binding through its oxygen atom to a surface La cation, with an adsorption energy of −2.2 eV and an equilibrium distance of 2.58 Å. The molecule remains strongly anchored to the substrate, and the analysis of the adsorption process points to a slight weakening of the C–O bond strengh, suggesting a potential starting point for surface-driven reaction pathways. Bond-order and structural analyses reveal La–O_molecule and La–O_surface bond lengths and bond orders of comparable magnitude, consistent with chemisorption. Adsorption also reduces the AlO–LaO interlayer spacing, reflecting charge redistribution within the perovskite lattice. The adsorption mechanism is further elucidated through complementary bond-order, bond-length, Bader-charge, and differential charge density analyses.

关键词： 1-methoxy-2-propanol   1-methoxy-2-propanone   Electrocatalytic oxidation   Electronic structure modulation   Mn–Ni(OH)2/NF  

摘要： Ni(OH)₂/NF demonstrates strong electrocatalytic performance in the oxidation of 1-methoxy-2-propanol (MOP) to 1-methoxy-2-propanone (MOA). However, its catalytic efficiency is restricted by two sluggish dehydrogenation stages: the oxidation of Ni^2 + –OH to generate the active Ni³⁺–O intermediate, and the abstraction of the α-hydrogen from the MOP molecule. To address these limitations, the present study introduces a strategy centered on tuning the electronic structure. By incorporating manganese (Mn) into the coordination structure of Ni(OH)₂/NF nanosheets in a controlled manner, both reaction steps are effectively enhanced through synergistic effects. X-ray photoelectron spectroscopy (XPS) and synchrotron-based X-ray absorption fine structure (XAFS) analyses reveal that Mn incorporation modifies the local electronic environment of Ni through electronic interactions. This adjustment decreases the d-orbital electron density of Ni, thereby facilitating the oxidation of Ni²⁺ to the catalytically active Ni³⁺ species during MOP conversion. Electrochemical measurements combined with density functional theory (DFT) calculations indicate that Mn incorporation markedly enhances the adsorption of MOP molecules on the catalyst surface, which thereby promotes more efficient reaction kinetics. This synergistic regulation effectively lowers the energy barrier associated with the dual dehydrogenation steps, resulting in markedly improved catalytic performance of Mn–Ni(OH)₂/NF for MOP oxidation, with the product Faradaic efficiency reaching around 90 %.

关键词： Biocorrosion   Density functional theory   Electrochemical potential shift   Passivation   Surface adsorption   Zr-rich multicomponent alloy  

摘要： Metallic bioimplants frequently experience corrosion in physiological environments, resulting in chronic inflammation and failure. A combined DFT and experimental study is proposed for the newly synthesized Zr50–Ti40–Nb5–Ta5 multicomponent alloy (MCA) and a comparison is made with the existing Ti MCA to benchmark corrosion behavior. Adsorption studies involving physiologically relevant corrosive species reveal preferential binding at (1 0 0) surface hollow sites on both alloy surfaces. While Ti MCA exhibits stronger adsorption energies, Zr MCA displays a positive electrochemical potential shift upon O₂ and –OH adsorption, indicative of enhanced surface passivation and corrosion resistance. In contrast, Cl^- adsorption induces negative shift which leads to surface destabilization with less pronounced effect in Zr MCA. Potentiodynamic polarization in Phosphate Buffer Solution (PBS) shows that Zr MCA achieves an extremely low corrosion current density and corrosion rate with a wide passive window. A stable transpassive region followed by rapid repassivation is observed indicating strong self-healing behavior of the passive film even at high anodic potentials. Electrochemical Impedance Spectroscopy shows a compact passive layer with high charge transfer resistance (314.03 ± 2.35 kΩ) and thickness of 5.94 ± 0.54 nm. SEM-EDS indicates a dense multicomponent oxide layer without any localized breakdown, supporting electrochemical evidence of chloride-resistant passivation.

关键词： Convex integration   Non-uniqueness   The incompressible Hall-MHD equations   Weak solutions  

摘要： In this paper, we focus on the three-dimensional hyper viscous and resistive Hall-MHD equations on the torus, where the viscous and resistive exponent $\alpha \in [\rho ,5/4)$ with a fixed constant $\rho \in (1,5/4)$. We prove the non-uniqueness of a class of weak solutions to the Hall-MHD equations, which have bounded kinetic energy and are smooth in time outside a set whose Hausdorff dimension is strictly less than 1. The proof is based on the construction of the non-Leray–Hopf weak solutions via a convex integration scheme. Due to the appearance of the Hall term, we reconstruct the errors, the intermittent flows and a temporal corrector in the convex integration.

关键词： Depression   Occupation   Work functioning   Scale validation   Major depressive disorder   Clinical trials   Measurement-based care  

摘要： Major depressive disorder (MDD) is associated with significant impairment in occupational functioning. The Lam Employment Absence and Productivity Scale (LEAPS) is a self-report questionnaire validated for the assessment of work productivity and absenteeism in patients with MDD. Our study objective was to establish a minimal clinically important difference (MCID) for the LEAPS.

关键词： Apoptosis   Autophagy   Bax   Bcl-2   Beclin-1   Caspase-9   Cleaved PARP   Hydrazonothiazolidin-4-ones   LC3-II   Malic enzyme-1   Scaffold hopping   Topoisomerase II   [2.2]Paracyclophanyl-hydrazinecarbothioamides  

摘要： Two series of [2.2]paracyclophanylthiazoles 5a–h and 7a–e were rationally designed, synthesized, and screened for anticancer activity against breast cancer cell lines representing both luminal (MCF-7) and aggressive (MDA-MB-231) subtypes, as well as safety profiling by a normal epithelial breast cell line MCF-10A. Of these, thiazolidinone derivatives 7a, 7d, and 7e possessed outstanding dual antiproliferative potency against MCF-7 (IC₅₀ = 3.1 ± 0.17, 3.76 ± 0.08, 1.19 ± 0.07 μM) and MDA-MB-231 (IC₅₀ = 1.04 ± 0.07, 1.08 ± 0.05, 2.50 ± 0.12 μM), significantly better than doxorubicin (IC₅₀ = 6.87 ± 0.18 μM and 4.16 ± 0.13 μM, respectively). Thiosemicarbazide derivative 3d also showed impressive cytotoxic potency against MCF-7 cells (IC₅₀ = 4.74 ± 0.14 μM). All four compounds were also safe for normal MCF-10A cells. Mechanistic studies revealed that most active derivatives engaged both autophagy and apoptosis pathways by modulating Beclin-1, Bax, Bcl-2, and caspase-9 with compound 7a validated by LC3-II and cleaved PARP assays. In addition, compounds 7a and 7e exhibited robust topo II inhibitory activity, whereas 7a and 7d efficiently disabled ME-1 function, both of which exhibited better IC₅₀ values than doxorubicin. Such biological results were also reinforced by molecular docking studies, which confirmed desirable binding of active candidates by topo II and ME-1 active sites, along with reasonable scoring energies and accepted physiochemical properties. Overall, these studies recognize paracyclophanyl-thiazolidinone hybrid 7a as a potential dual topo II/ME-1 inhibitor of clinical interest for treating triple-negative breast cancer (TNBC).

关键词： 1,3,5-trioxane   Ionic liquids   Molecular dynamics simulation   Quantum chemical calculation   Liquid-liquid extraction  

摘要： Direct extraction of 1,3,5-trioxane from formaldehyde aqueous solutions is critical for producing high-purity 1,3,5-trioxane, an essential monomer in the synthesis of polyoxymethylene and other value-added chemicals. In this work, the 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([OMIM][Tf₂N]) was identified from 625 potential ionic liquids (ILs) via COSMO-RS screening as a replacement for toxic solvents (e.g., benzene/dichloromethane). Crucially, methylene glycol (MG), the dominant formaldehyde hydrate governing dynamic equilibria, was incorporated to reflect industrial conditions, which represents a key advance over prior simplified models. Quantum chemical calculations revealed van der Waals interactions (dominated by [OMIM]⁺) as the primary driver for 1,3,5-trioxane extraction with weak hydrogen bonds. Molecular dynamics simulations were performed to explore the extraction experimental conditions, and the simulation results were in good agreement with the experimental data. Optimal operating conditions were experimentally determined as 338.15 K and solvent-to-feed ratio 1.5:1, with > 87% 1,3,5-trioxane recovery and selectivity > 35 obtained in single-stage liquid–liquid extraction experiments. Compared with other high-temperature processes, the IL-based process significantly mitigates the risk of formaldehyde monomer leakage and enables solvent recyclability, offering a sustainable and industrially viable alternative.

关键词： Aptamer   CRISPR/Cas12a   Dual-readout   KIM-1 detection   Kidney transplant   Nanozyme  

摘要： Kidney injury molecule-1 (KIM-1) has emerged as a pivotal prognostic biomarker for renal allograft function. However, its detection remains challenging due to sensitivity and accuracy limitations. An innovative biosensing platform synergizing aptamer recognition, CRISPR trans-cleavage and nanozyme amplification for dual-readout KIM-1 detection has been presented in this work. This platform employs a meticulously selected high-affinity aptamer with capillary electrophoresis SELEX for specific target recognition, leverages the CRISPR/Cas12a system for signal transduction and cascade amplification, and utilizes engineered FeNi MOF@AgNPs nanozyme for dual-signal output. With the presence of KIM-1, whose binding with aptamer, effectively inhibits the trans-cleavage activity of the CRISPR/Cas12a system, and uninhibited Cas12a subsequently cleaves nanozyme-conjugated magnetic probes, releasing FeNi MOF@AgNPs nanozymes that catalyze a TMB-based reaction to generate intense colorimetric and fluorescent dual-readout signals. The as developed aptasensor demonstrates satisfied sensitivity achieving detection limits of 58.7 pg/mL (colorimetric) and 34.4 pg/mL (fluorometric), and dependable accuracy achieving average relative deviation of −2.7% (colorimetric) and 3.2% (fluorometric) with commercial ELISA kit in urine samples from patients with acute kidney injury. Moreover, longitudinally track the dynamic changes in urinary KIM-1 concentrations over the first 8 days following renal transplantation was successfully realized. This work not only provides a robust analytical tool for KIM-1 detection but also establishes a generic research approach for extending CRISPR-based systems to the precise detection of proteins.