Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine

Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.     

The structure,vacancy characteristics,and magnetic properties of GdMn1-xCrxO3 ceramics

To investigate the evolution of the structural and enhanced magnetic properties of GdMnO₃ systems induced by the substitution of Mn with Cr, polycrystalline GdMn_1-xCr_xO₃ samples were synthesized via solid-state reactions. XRD characterization shows that all GdMn_1-xCr_xO₃ compounds with single-phase structures crystallize well and that Cr³⁺ ions entering the lattice sites of GdMnO₃ induce structural distortion. SEM results indicate that the grain size of the synthesized samples (a few microns) decreases as the Cr substitution concentration increases. Positron annihilation lifetime spectroscopy reveals that vacancy-type defects occur in GdMn_1-xCr_xO₃ ceramics and that the vacancy size and concentration clearly change with the Cr content. The temperature and field dependence of the magnetization curves show that Cr substitution significantly influences the magnetic ordering of the gadolinium sublattice, improving the weak ferromagnetic transition temperature and magnetization of GdMn_1-xCr_xO₃. The enhanced magnetization of GdMn_1-xCr_xO₃ is closely related to the vacancy defect concentration.     

Superradiant Emission from Coherent Excitons in van Der Waals Heterostructures

Recent advancements in isolation and stacking of layered van der Waals materials have created an unprecedented paradigm for demonstrating varieties of 2D quantum materials. Rationally designed van der Waals heterostructures composed of monolayer transition-metal dichalcogenides (TMDs) and few-layer hBN show several unique optoelectronic features driven by correlations. However, entangled superradiant excitonic species in such systems have not been observed before. In this report, it is demonstrated that strong suppression of phonon population at low temperature results in a formation of a coherent excitonic-dipoles ensemble in the heterostructure, and the collective oscillation of those dipoles stimulates a robust phase synchronized ultra-narrow band superradiant emission even at extremely low pumping intensity. Such emitters are in high demand for a multitude of applications, including fundamental research on many-body correlations and other state-of-the-art technologies. This timely demonstration paves the way for further exploration of ultralow-threshold quantum-emitting devices with unmatched design freedom and spectral tunability.     

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Interfacial microstructure and mechanical properties of Ti3SiC2 ceramic and TC11 alloy joint diffusion bonded with a Cu interlayer

Reliable joints of Ti₃SiC₂ ceramic and TC11 alloy were diffusion bonded with a 50 μm thick Cu interlayer. The typical interfacial structure of the diffusion boned joint, which was dependent on the interdiffusion and chemical reactions between Al, Si and Ti atoms from the base materials and Cu interlayer, was TC11/α-Ti + β-Ti + Ti₂Cu + TiCu/Ti₅Si₄ + TiSiCu/Cu(s, s)/Ti₃SiC₂. The influence of bonding temperature and time on the interfacial structure and mechanical properties of Ti₃SiC₂/Cu/TC11 joint was analyzed. With the increase of bonding temperature and time, the joint shear strength was gradually increased due to enhanced atomic diffusion. However, the thickness of Ti₅Si₄ and TiSiCu layers with high microhardness increased for a long holding time, resulting in the reduction of bonding strength. The maximum shear strength of 251 ± 6 MPa was obtained for the joint diffusion bonded at 850 °C for 60 min, and fracture primarily occurred at the diffusion layer adjacent to the Ti₃SiC₂ substrate. This work provided an economical and convenient solution for broadening the engineering application of Ti₃SiC₂ ceramic.     

Wall Rock Alteration,Uranium Mineralization,and Potentiality of Uranium and Iron Dissolution from Mineralized Abu Rusheid Gneiss Rock,South Eastern Desert,Egypt

Radiochemistry - Ferrugination, sericitization, desulfitization, chloritization, and kaolinitization of hydrothermal origin are the main wall rock alterations occurring within the NNW shear zones...     

Granulation Tissue Enhanced with Aspirin and Omega-3 PUFAs as a Local Adjunct to the Surgical Treatment of Periodontitis

The topical application of aspirin and omega-3 polyunsaturated fatty acids (PUFAs) may trigger the resolution of inflammation by inducing the biosynthesis of pro-resolvers such as lipoxins and resolvins while also avoiding the side effects of systemic aspirin intake. This study assessed the effect of enhanced granulation tissue (EGT) on periodontal tissue regeneration through the local application of aspirin and omega-3 PUFAs directly to granulation tissue (GT) during periodontal surgery. This randomized controlled experiment assesses 38 pockets in 19 patients. In every patient, two similar intrabony periodontal defects are treated with an open flap debridement, one with EGT (GT extracted, enhanced with aspirin and omega-3 PUFAs, and replaced) and the other with standard GT removal. Clinical attachment level (CAL) and probing pocket depth (PPD) are assessed at baseline and 2 and 6 months after surgery. The experimental protocol (EGT) results in a greater CAL gain as compared to that in the controls at 6 months (p < 0.05), while PPD reduction is not affected. The retained GT does not compromise healing. EGT is proposed as a promising, inexpensive, and simple method that may improve the outcome of periodontal regenerative treatment. However, the described protocol requires optimization and further assessment. Practical Applications : The biosynthesis of mediators including resolvins and lipoxins triggered by aspirin and omega-3 PUFAs promote the resolution of inflammation, eventually leading to faster regeneration of inflamed tissues. While granulation tissue is a necessary component in wound healing, enhancing granulation tissue with aspirin and omega-3 PUFAs results in CAL gain in the surgical treatment of periodontal defects. Retained granulation tissue does not compromise periodontal healing. The EGT strategy is an inexpensive and simple method that may improve the clinical outcomes of regenerative periodontal procedures.     

Hydraulic reactivity and cement formation of baghdadite

In this study, the hydraulic reactivity and cement formation of baghdadite (Ca₃ZrSi₂O₉) was investigated. The material was synthesized by sintering a mixture of CaCO₃, SiO₂, and ZrO₂ and then mechanically activated using a planetary mill. This leads to a decrease in particle and crystallite size and a partial amorphization of baghdadite as shown by X-ray powder diffraction (XRD) and laser diffraction measurements. Baghdadite cements were formed by the addition of water at a powder to liquid ratio of 2.0 g/ml. Maximum compressive strengths were found to be ~2 MPa after 3-day setting for a 24-h ground material. Inductively coupled plasma mass spectrometry (ICP-MS) measurements showed an incongruent dissolution profile of set cements with a preferred dissolution of calcium and only marginal release of zirconium ions. Cement formation occurs under alkaline conditions, whereas the unground raw powder leads to a pH of 11.9 during setting, while prolonged grinding increased pH values to approximately 12.3.     

Chemoenzymatic Asymmetric Synthesis of Pyridine-Based α-Fluorinated Secondary Alcohols

Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield.