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.     

Induced slim ferroelectric hysteresis loops and enhanced energy-storage properties of Mn-doped (Pb0·93La0.07)(Zr0·82Ti0.18)O3 anti-ferroelectric thick films by aerosol deposition

In this study, the high ferroelectric hysteresis loss of (Pb_0·93La_0.07)(Zr_0·82Ti_0.18)O₃ (PLZT 7/82/18) antiferroelectric (AFE) ceramics was reduced by employing a combinatorial approach of Mn acceptor doping followed by thick film fabrication via an aerosol deposition (AD) process. The grains of the as-deposited PLZT 7/82/18 AFE AD thick films were grown by thermal annealing at 550 °C to enhance their electrical properties. Investigation of the electrical properties revealed that Mn-doping results in improved dielectric and ferroelectric properties, increased dielectric breakdown strength (DBS), and energy-storage properties. The Mn-doped PLZT AFE AD films possess a frequency-independent high dielectric constant (ε_r ≈ 660) with low dielectric loss (tan δ ≈ 0.0146), making them suitable candidates for storage capacitor applications. The bipolar and unipolar polarization vs. electric field (P-E) hysteresis loops of PLZT 7/82/18 AFE AD thick films were found to be slimmer than those of their bulk form (double hysteresis) with significantly reduced ferroelectric hysteresis loss, which is attributed to the AD-induced mixed grain structure. The Mn-doped PLZT 7/82/18 AFE AD thick films exhibited a low remnant polarization (P_r ≈ 9.22 μC/cm²) at a high applied electric field (~2750 kV/cm). The energy-storage density and energy efficiency of the Mn-doped PLZT AFE AD thick films were calculated from unipolar P-E hysteresis loops and found to be ~38.33 J/cm³ and ~74%, respectively.     

High energy storage and ultrafast discharge in NaNbO3-based lead-free dielectric capacitors via a relaxor strategy

Dielectric capacitors with decent energy storage and fast charge-discharge performances are essential in advanced pulsed power systems. In this study, novel ceramics (1-x)NaNbO₃-xBi(Ni_2/3Nb_1/3)O₃(xBNN, x = 0.05, 0.1, 0.15 and 0.20) with high energy storage capability, large power density and ultrafast discharge speed were designed and prepared. The impedance analysis proves that the introducing an appropriate amount of Bi(Ni_0·5Nb_0.5)O₃ boosts the insulation ability, thus obtaining a high breakdown strength (E_b) of 440 kV/cm in xBNN ceramics. A high energy storage density (W_total) of 4.09 J/cm³, recoverable energy storage density (W_rec) of 3.31 J/cm³, and efficiency (η) of 80.9% were attained in the 0.15BNN ceramics. Furthermore, frequency and temperature stability (fluctuations of W_rec ≤ 0.4% over 5–100 Hz and W_rec ≤ 12.3% over 20–120 °C) were also observed. The 0.15BNN ceramics exhibited a large power density (19 MW/cm³) and ultrafast discharge time (~37 ns) over the range of ambient temperature to 120 °C. These enhanced performances may be attributed to the improved breakdown strength and relaxor behavior through the incorporation of BNN. In conclusion, these findings indicate that 0.15BNN ceramics may serve as promising materials for pulsed power systems.     

Design of Ti4+-doped Li3V2(PO4)3/C fibers for lithium energy storage

In this work, we propose a facile approach to fabricate Ti⁴⁺-doped Li₃V₂(PO₄)₃/C (abbreviated as C-LVTP) nanofibers using an electrospinning route followed by a high temperature treatment. In this designed nanocomposite, the ultrafine LVTP dots are homogeneously dispersed into one-dimensional carbon nanofibers and the Ti⁴⁺ doping does not destroy the crystal structure of monoclinic Li₃V₂(PO₄)₃. Compared to the undoped Li₃V₂(PO₄)₃/C (abbreviated as C-LVP), the as-fabricated C-LVTP fibers present higher reversible capacity, superior high-rate capability as well as better cyclic property. Especially, the C-LVT_7%P cathode delivers not only high capacities of 187.2 and 160.3 mAh g^?1 at 0.5 and 10 C respectively, but also stable cyclic property with the reversible capacity of 135.8 mAh g^?1 at 20 C following 500-cycle spans. The good battery characteristics of C-LVT_7%P can be mainly ascribed to Ti⁴⁺ doping, which can increase the electrical conductivity and Li⁺ diffusion coefficient.     

Catalytic combustion synthesis of CNTs/MgO composite powders and the influences on the thermal shock resistance of low-carbon Al2O3–C refractories

Using MgC₂O₄, Mg powders as raw materials and Ni(NO₃)₂?6H₂O as a catalyst, CNTs/MgO composite powders were prepared by a catalytic combustion synthesis method. The CNTs/MgO composite powders were characterized by XRD, Raman spectroscopy, FESEM/EDS and HRTEM. The effects of catalyst content on the degree of graphitization and aspect ratio of the CNTs in composite powders were investigated. Moreover, the thermal shock resistance of low-carbon Al₂O₃–C refractories after adding the composite powder was investigated. The results indicated that the CNTs prepared with 1 wt% Ni(NO₃)₂?6H₂O addition had a higher degree of graphitization and aspect ratio. In particular, the aspect ratio could reach approximately 200. The growth mechanism of hollow bamboo-like CNTs in the composite powders was proven to be a V-L-S mechanism. The thermal shock resistance of Al₂O₃–C samples could be improved significantly after adding CNTs/MgO composite powders. In particular, compared with CM0, the residual strength ratio of Al₂O₃–C samples with added 2.5 wt% composite powders could be increased 63.9%.     

Preparation of high-purity SiC ceramics with good plasma corrosion resistance by hot-pressing sintering

High-purity SiC ceramic devices are applied in semiconductor industry owing to their outstanding properties. Nevertheless, it is difficult to densify SiC ceramics without any sintering additive even by HP sintering. In this work, high-purity and dense SiC ceramics were fabricated by HP sintering with very low amounts of sintering aids. Residual B content was only 556 ppm and relative density was more than 99.5%. Furthermore, thermal conductivity of as-prepared SiC ceramics was improved from 155 W m^?1 K^?1 to 167 W m^?1 K^?1 by increasing holding time and their plasma corrosion resistance was promoted in the meantime. The as-prepared high-purity SiC ceramics have broad application prospects in the field of semiconductor industry.     

Microstructure,mechanical, tribological,and oxidizing properties of AlCrSiN/AlCrVN/AlCrNbN multilayer coatings with different modulated thicknesses

Multilayer structure design is one of the most promising methods for improving the comprehensive performance of AlCrN-based hard coatings applied to cutting tools. In this study, four types of AlCrSiN/AlCrVN/AlCrNbN multilayer coatings, with different modulated thicknesses, were deposited to investigate their microstructure, mechanical, tribological, and oxidizing properties. All multilayer coatings exhibited grain growth along the crystallographic plane of (200) with a NaCl-type face-centered cubic (FCC) structure. The results show that, as the modulation thickness decreases from ～35 nm to ～10 nm, (1) the grain refinement effect is increasingly evident; (2) all multilayer coatings show a hardness of >30 GPa and an elastic modulus of >300 GPa. Both the ability to resist elastic strain to failure and the plastic deformation of multilayer coatings increase. In addition, their resistance to cracking reduces; (3) the wear rates of these multilayer coatings reduce successively from 1.78 × 10^?16 m³ N^?1 m^?1 to 7.7 × 10^?17 m³ N^?1 m^?1. This is attributed to an increase in self-lubricating VO_x and a decrease in adhesives from the counterparts; (4) the best high-temperature oxidation resistance was obtained for the multilayer coating with a modulated thickness of ～15 nm.     

Structure,mechanical and thermal properties of Y-doped CrAlN coatings

CrAlYN coatings with different Y contents (0, 5 and 12 at.%) were deposited by cathodic arc evaporation to investigate the influence of Y-addition on the structure, mechanical and thermal properties of CrAlN coatings by using X-ray diffraction, scanning electron microscopy, differential scanning calorimetry, thermal gravimetric analysis and nanoindentation. The structural transformation of single phase cubic Cr_0.42Al_0.58N and Cr_0.39Al_0.56Y_0.05N coatings to cubic–wurtzite mixed Cr_0.32Al_0.56Y_0.12N coating leads to a drop in hardness from (30.2±0.7) GPa of Cr_0.42Al_0.58N and (32.0±1.0) GPa of Cr_0.39Al_0.56Y_0.05N to (25.2±0.7) GPa of Cr_0.32Al_0.56Y_0.12N. The incorporation of 5 at.% Y retards the thermal decomposition of CrAlN, verified by the postponed precipitation of w-AlN and N-loss upon annealing. Correspondingly, Cr_0.39Al_0.56Y_0.05N coating consistently exhibits the highest hardness value during thermal annealing. Nevertheless, alloying with Y exerts an adverse effect on the oxidation resistance of CrAlN.