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Abstract: CLK1 is one of the four human isoforms of the cdc2-like (CLK) kinases that has been suggested as a therapeutic target in diverse diseases based on its important role regulating mRNA splicing. For example, CLKs and closely related kinases such as DYRK1A have been targeted in Alzheimer’s disease and other diseases in which splice site selection contributes to the disease development. Here we have developed an efficient in silico fragment-based ligand design approach to identify novel CLK1 inhibitors with excellent ligand efficiency based on an imidazo[2,1-b][1,3,4]thiadiazole fragment. More than one million docking poses were generated from 26,225 unique virtual compounds, and after applying several filtering steps, 11 compounds were selected, synthesized and their CLK1 inhibition and cellular potency were evaluated. Gratifyingly, inhibitor potencies were in excellent agreement with predicted values and crystallographic data of an inhibitor bound to CLK1 confirmed the unusual binding mode of the compounds.

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Abstract: Colloidal quantum dots (QDs) represent a versatile class of luminescent nanomaterials whose physicochemical and interfacial properties can be engineered for advanced bio-related applications. Herein, the wet-precipitation synthesis and surface engineering of ultra-small fluorine-doped ZnO quantum dots (F/ZnO QDs) were proposed and their formulation into stable amphiphilic nanosystems using synthetic glycoglycerolipids. To control aggregation and interfacial behavior, the QDs were first capped with oleylamine and subsequently functionalized through an emulsion-based approach with mono-acyl or di-acyl glycoglycerolipids, yielding double-coated amphiphilic nanoformulations. The resulting materials were extensively characterized by TEM, DLS, zeta-potential measurements, XRD, FTIR/ATR, UV–Vis, and fluorescence spectroscopy, allowing to explore correlations between surface chemistry, colloidal stability, and optical properties. Glycoglycerolipid functionalization led to a marked improvement in aqueous dispersibility and long-term colloidal stability while preserving the enhanced fluorescence induced by fluorine doping. Biological assays confirmed the cytocompatibility of the coated QDs and supported their suitability for further biointerface studies. This work highlights glycoglycerolipid-based amphiphilic coatings as an effective strategy to tailor the surface and colloidal properties of ZnO-based QDs, enabling the development of stable luminescent nanomaterials as biocompatible nanoprobes and for bio-interfacial applications.

Open Access

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Abstract: The β′-Gd2(MoO4)3 phase is one of the most well-known multiferroic materials, exhibiting both ferroelectricity and ferroelasticity under ambient conditions, with a complex temperature-pressure phase diagram. In this study, we review the pressure-dependent behavior of the RE2(MoO4)3 compound family (where RE ≡ Pr–Ho), which crystallizes in the β′-phase, with the β-phase being the paraelectric parent structure. Eu, Tb, and Ho molybdates were synthesized via solid-state reactions, ensuring the absence of impurities. High-pressure experiments at DIAMOND synchrotron revealed that the β′-phase persists at low-pressures. At approximately 2 GPa, new peaks emerged, which were refined as a mixture of the β′-phase, other rare-earth molybdates, and oxides, some of which have been detected in earlier stages of synthesis. The β′-phase became distorted with increasing pressure while coexisting with these new phases, whose average unit cell volume was found to lie between that of the β′-phase and the formed distorted phase. Ultimately, this multiphase crystalline decomposition acts as a precursor to pressure-induced amorphization, leading to a loss of long-range periodicity without complete loss of local order. The onsets of pressure-induced decomposition, distortion of the β′-phase and apparent amorphization increase as the ionic radius of the rare-earth element decreases. This scenario of irreversible structural disorder accumulated through phase coexistence is consistent with previous studies and resolves a debate persisting for over half a century.

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Abstract: A robust single-phase AC–AC chopper topology with a grounded load is proposed for compact, high-efficiency power conversion. The converter comprises one P-type and one N-type AC switching-cell leg, enabling four-quadrant operation while simultaneously being inherently immune to shoot-through conditions. The legs are connected to a grounded load via a coupled inductor, and together with a three-step switching strategy, form a topology that is tolerant to supply voltage polarity detection errors of at least ±20° around the mains zero-crossing, without the need for large, bulky snubbers. An analytic method is presented for sizing the current-limiting inductors, which accounts for the effects of circuit parasitics. SPICE simulations and measurements from a 1.5 kW GaN-based prototype validate the design, demonstrating low output voltage total harmonic distortion and high robustness. The converter is suitable for space-constrained, high-performance AC–AC conversion applications.

Open Access

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Abstract: The structural behaviour of homoleptic xenon difluoride (XeF2) com­plexes [M(XeF2)6][SbF6]2 (M = Cu, Zn) under varying tem­per­a­ture and pressure has been investigated, aiming to resolve the disordered Jahn–Teller distortions in the copper com­plex (CuSb). At 200 K, both CuSb and its zinc analogue (ZnSb) crystallize in a layered CdCl2-type structure with the space group R3. Upon cooling below 170 (CuSb) and 160 K (ZnSb), both systems transition to iso­structural phases in P1, with CuSb assuming an ordered Jahn–Teller distortion. The transformation is driven by the shortening and optimization of the Xe⋯F inter­molecular contacts, forming stronger and more directional inter­actions, rather than by Jahn–Teller effects alone. This is supported by the observation of similar transitions in the Jahn–Teller-inactive Zn system. High-pressure ex­peri­ments up to ∼2.8 GPa at room tem­per­a­ture show the structural stability of the high-symmetry phases, implicating kinetic barriers to further transformation. Additionally, the synthesis and structural characterization of a novel arsenic analogue, [Zn(XeF2)6][AsF6]2 (ZnAs), reveal similar layered motifs but distinct phase behaviour. Symmetry-mode analyses relate all observed phases through distortions of a common CdCl2 aristotype.