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Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple‐negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti‐cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the ubiquitin E3 ligase βTRCP in the form of molecular glue. C1 significantly inhibits the proliferation and metastasis of TNBC cells both in vitro and in vivo and in TNBC patient‐derived organoids, and these antitumor effects are attributed to the degradation of eEF2K by C1. Additionally, combination treatment of C1 with paclitaxel, a commonly used chemotherapeutic drug, exhibits synergistic anti‐tumor effects against TNBC. This study not only generates a powerful research tool to investigate the therapeutic potential of targeting eEF2K, but also provides a promising lead compound for developing novel drugs for the treatment of TNBC and other cancers. [ABSTRACT FROM AUTHOR]

The comparison and analysis of piezoelectric properties for [001]-oriented PMN-0.30PT by different polarization conditions were investigated. It should be noticed that the average piezoelectric coefficients d33 of PMN-0.30PT crystals were 1860 pC/N by alternating current (AC) polarization and 1380 pC/N by direct current (DC) polarization, which indicates a promotion of 35.3%. The domain patterns in the [001] surface of PMN-0.30PT single crystals under different polarization conditions are obtained by piezo-response force microscopy. The enhancement of piezoelectric performance by AC polarization is attributed to the regular stripe domains with high domain wall density. With the temperature increased to TR-T, both the values of dielectric constant ε r T and piezoelectric coefficients d33 under AC polarization condition maintain higher compared to traditional DC poled samples. In addition, both the values of e 33 and ε 33 S under AC polarization retain higher than that of DC polarization, suggesting that the special domain structure with high domain wall density by AC polarization keeps a stable state as the temperature increased to TR-T. When the temperature increased from TR-T to TT-C, the piezoelectric properties of crystals (ε r T and d33) under different polarization conditions become the same status, which indicates that the domain structure under the different conditions of polarization may tend to the similar state and the extrinsic contribution from the domain wall motion by AC polarization is disappeared. [ABSTRACT FROM AUTHOR]

The [111]‐oriented rhombohedral Mn‐doped 0.15Pb(In1/2Nb1/2)‐0.55Pb(Mg1/3Nb2/3)O3‐0.30PbTiO3 (Mn:PIMNT(15/55/30)) crystal and the [001]‐oriented tetragonal Mn‐doped 0.29Pb(In1/2Nb1/2)‐0.29Pb(Mg1/3Nb2/3)O3‐0.42PbTiO3 (Mn:PIMNT(29/29/42)) crystal were poled under different conditions. The pyroelectric performance of the two crystals as a function of poling temperature, as well as the relationship with ferroelectric domain configuration and phase structure was investigated systematically. The pyroelectric properties of the two crystals enhance with rising the poling temperature, which can be attributed to the improvement of the single state. And for the rhombohedral Mn:PIMNT(15/55/30) crystal locating near morphotropic phase boundary (MPB), the increase of tetragonal phase induces the deterioration of pyroelectric properties. Due to more residual tetragonal phase, the pyroelectric coefficient of the Mn:PIMNT(15/55/30) crystal poled at 150°C is lower than that poled at 100°C. In general, both the crystals poled above TC achieve nearly single state, exhibiting the best pyroelectric properties with relatively high Curie temperature (TC), where P = 9.71 × 10−4 C m−2 K−1, Fi = 3.88 × 10−10 m V−1, Fv = 0.068 m2 C−1 and Fd = 29.7 × 10−5 Pa−1/2 for the rhombohedral Mn:PIMNT(15/55/30) crystal (TC = 171°C) and P = 6.78 × 10−4 C m−2 K−1, Fi = 2.71 ×10−10 mV−1, Fv = 0.1 m2 C−1, Fd = 23.54 × 10−5 Pa−1/2 for the tetragonal Mn:PIMNT(29/29/42) single crystal (TC = 251°C), meeting the stable operation of infrared detector at relatively high environmental temperatures. [ABSTRACT FROM AUTHOR]

The dielectric, ferroelectric and piezoelectric properties of the high-Curie temperature (high-T C ) 0.15Pb(Mg 1/3 Nb 2/3 )O 3 -0.38PbHfO 3 -0.47PbTiO 3 (0.15PMN-0.38PH-0.47PT) ceramics synthesized by three different methods were investigated. The 0.15PMN-0.38PH-0.47PT ceramics prepared by the partial oxalate route present the best electrical properties (T C = 291 °C, ε m = 28,937, P r = 32.89 μC/cm 2 , E c = 9.35 kV/cm, d 33 = 456.2 pC/N and K p = 67.2%) and excellent thermal stability of the piezoactivity properties under T C . Piezoresponse force microscopy (PFM) and confocal Raman microscopy (CRM) were employed to probe the nanoscale mechanism responsible for the performance difference of the 0.15PMN-0.38PH-0.47PT ceramics prepared by three different methods, disclosing the existence of the fine stripe domains, which make up the big island domains. The interplay between the macroscopic properties and nanoscopic domain structures of the 0.15PMN-0.38PH-0.47PT ceramics has been revealed. The better ferroelectric and piezoelectric response arise from the smaller domain size, which reduces the domain wall energy; whereas the higher coercive field E c detected by the polarization-electric field (P-E) loops results from the harder domain switching for the 0.15PMN-0.38PH-0.47PT ceramics prepared by the wet chemical synthesis techniques. [ABSTRACT FROM AUTHOR]

The ferroelectric phase transition characteristics of the 0.32Pb(In1/2Nb1/2)O3-0.345Pb(Mg1/3Nb2/3)O3-0.335PbTiO3(0.32PIN-0.345PMN-0.335PT) single crystals were studied by the temperature-dependent Raman spectroscopy and some electrical properties. Ferroelectric monoclinic phase was confirmed at room temperature by the numbers of the Raman modes. Successive ferroelectric phase transitions, i.e. ferroelectric monoclinic phase to ferroelectric tetragonal phase transition (FEM-FET) and ferroelectric tetragonal phase to paraelectric cubic phase transition (FET-PC), are evidenced by the anomalies of Raman modes line width, peaks intensity and their ratios aroundTM-TandTC/Tmtemperatures. The temperature dependent permittivity derivative ξ =dϵ/dTnot only provides further evidence of the successive ferroelectric phase transitions, but also demonstrates the second-order transition characteristic of the FEM-FETphase transition and the first-order transition feature of the FET-PCphase transition. The FEM-FETphase transition is also confirmed by the abnormal narrowing of the P-E loops, decrease of thePrandEcvalues, and extremums of the pyroelectric performance. [ABSTRACT FROM PUBLISHER]

The widely conserved multiple antibiotic resistance regulator (MarR) family of transcription factors modulates bacterial detoxification in response to diverse antibiotics, toxic chemicals or both. The natural inducer for Escherichia coli MarR, the prototypical transcription repressor within this family, remains unknown. Here we show that copper signaling potentiates MarR derepression in E. coli. Copper(II) oxidizes a cysteine residue (Cys80) on MarR to generate disulfide bonds between two MarR dimers, thereby inducing tetramer formation and the dissociation of MarR from its cognate promoter DNA. We further discovered that salicylate, a putative MarR inducer, and the clinically important bactericidal antibiotics norfloxacin and ampicillin all stimulate intracellular copper elevation, most likely through oxidative impairment of copper-dependent envelope proteins, including NADH dehydrogenase-2. This membrane-associated copper oxidation and liberation process derepresses MarR, causing increased bacterial antibiotic resistance. Our study reveals that this bacterial transcription regulator senses copper(II) as a natural signal to cope with stress caused by antibiotics or the environment. [ABSTRACT FROM AUTHOR]