Aneuploidy, an incorrect chromosome number, is a hallmark of cancer. Compounds that cause lethality in aneuploid, but not euploid, cells could therefore provide new cancer therapies. We have ...identified the energy stress-inducing agent AICAR, the protein folding inhibitor 17-AAG, and the autophagy inhibitor chloroquine as exhibiting this property. AICAR induces p53-mediated apoptosis in primary mouse embryonic fibroblasts (MEFs) trisomic for chromosome 1, 13, 16, or 19. AICAR and 17-AAG, especially when combined, also show efficacy against aneuploid human cancer cell lines. Our results suggest that compounds that interfere with pathways that are essential for the survival of aneuploid cells could serve as a new treatment strategy against a broad spectrum of human tumors.
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► 4 trisomic MEF lines were screened for compounds that antagonize their proliferation ► The AMPK agonist AICAR and the Hsp90 inhibitor 17-AAG induce apoptosis in trisomic MEFs ► AICAR increases already elevated levels of Hsp72 and autophagy in trisomic MEFs ► AICAR+17-AAG preferentially inhibit the growth of high-grade aneuploid cancer cells
The interplay between light and matter is the basis of many fundamental processes and various applications. Harnessing light-matter interactions in principle allows operation of solid state devices ...under new physical principles: for example, the a.c. optical Stark effect (OSE) has enabled coherent quantum control schemes of spins in semiconductors, with the potential for realizing quantum devices based on spin qubits. However, as the dimension of semiconductors is reduced, light-matter coupling is typically weakened, thus limiting applications at the nanoscale. Recent experiments have demonstrated significant enhancement of nanoscale light-matter interactions, albeit with the need for a high-finesse cavity, ultimately preventing device down-scaling and integration. Here we report that a sizable OSE can be achieved at substantial energy detuning in a cavity-free colloidal metal-semiconductor core-shell hetero-nanostructure, in which the metal surface plasmon is tuned to resonate spectrally with a semiconductor exciton transition. We further demonstrate that this resonantly enhanced OSE exhibits polarization dependence and provides a viable mechanism for coherent ultrafast spin manipulation within colloidal nanostructures. The plasmon-exciton resonant nature further enables tailoring of both OSE and spin manipulation by tuning plasmon resonance intensity and frequency. These results open a pathway for tailoring light-matter-spin interactions through plasmon-exciton resonant coupling in a judiciously engineered nanostructure, and offer a basis for future applications in quantum information processing at the nanoscale. More generally, integrated nanostructures with resonantly enhanced light-matter interactions should serve as a test bed for other emerging fields, including nano-biophotonics and nano-energy.
Manipulating ferroic orders and realizing their coupling in multiferroics at room temperature are promising for designing future multifunctional devices. Single external stimulation has been ...extensively proved to demonstrate the ability of ferroelastic switching in multiferroic oxides, which is crucial to bridge the ferroelectricity and magnetism. However, it is still challenging to directly realize multi‐field‐driven magnetoelectric coupling in multiferroic oxides as potential multifunctional electrical devices. Here, novel magneto–electric–optical coupling in multiferroic BiFeO3‐based thin films at room temperature mediated by deterministic ferroelastic switching using piezoresponse/magnetic force microscopy and aberration‐corrected transmission electron microscopy are shown. Reversible photoinduced ferroelastic switching exhibiting magnetoelectric responses is confirmed in BiFeO3‐based films, which works at flexible strain states. This work directly demonstrates room‐temperature magneto–electric–optical coupling in multiferroic films, which provides a framework for designing potential multi‐field‐driven magnetoelectric devices such as energy conservation memories.
The magneto–electric–optical coupling is realized in multiferroic BiFeO3‐based films at room temperature by engineering ferroelastic switching. The reversible ferroelastic switching is ubiquitous in BiFeO3‐based films with flexible strain states and domain patterns, which is determined by the photoinduced electric field and symmetry mismatch in films. This work provides a framework for multi‐field‐driven magnetoelectric memories with low power consumption.
Molecular ferroelectrics with high-temperature reversible phase-transition behaviors are very rare and have currently become one of the hotspots in the field of ferroelectric materials. Herein we ...display two new crown ether clathrates possessing unusual high-temperature ferroelectric phase-transition behaviors, cyclohexyl ammonium 18-crown-6 tetrafluoroborate (or perchlorate), Hcha-(18-crown-6)+ BF4− (1) and Hcha-(18-crown-6)+ClO4− (2) (Hcha = protonated cyclohexyl ammonium). We have proven their reversible structural phase transitions by variable-temperature PXRD measurements and temperature evolutions of Raman bands. Both clathrates exhibit clear ferroelectric phase transitions at about 397 and 390 K, respectively, revealed by the thermal anomalies of differential scanning calorimetry (DSC) measurements, together with abrupt dielectric anomalies in the heating and cooling processes. The measurements on ferroelectric properties using the single crystals showed optimized spontaneous polarization (P s) of ca. 3.27 μC cm–2 for 1 and 3.78 μC cm–2 for 2.
Abstract This work analyzes the present-day mass function (PDMF) of 93 star clusters utilizing Gaia Data Release 3 data, with membership determined by the StarGo machine-learning algorithm. The ...impact of unresolved binary systems on mass estimation is rigorously assessed, adopting three mass ratio profiles for correction. The PDMF is characterized by the power-law index, α , derived through a robust maximum likelihood method that avoids biases associated with data binning. The value of α for stars between the completeness limited mass of Gaia (with a mean 0.3 M ⊙ for our cluster samples) and 2 M ⊙ exhibits stability for clusters younger than 200 Myr, decreasing for older clusters, particularly when considering stars within the half-mass radius. The PDMF of these star clusters is consistent with a dynamically evolved Kroupa initial mass function via the loss of low-mass stars. Cluster morphology shows a correlation with α , as α values exhibit a decreasing trend from filamentary to tidal-tail clusters, mirroring the sequence of increasing cluster age. The dependence of α on the total cluster mass is weak, with a subtle increase for higher-mass clusters, especially outside the half-mass radius. We do not observe a correlation between α and the mean metallicity of the clusters. Younger clusters have lower metallicity compared to their older counterparts, which indicates that the older clusters might have migrated to the solar neighborhood from the inner disk. A comparison with numerical models incorporating a black hole population suggests the need for observations of distant, older, massive open clusters to determine whether or not they contain black holes.
Smart multifunctional molecular ferroelectrics bearing high Curie temperatures and diverse excellent physical properties, such as second harmonic generation (SHG) responses, luminescence, and ...semiconductivity, among others, have significant applications but have seldom been documented. Herein, the rare‐earth metals Nd and Pr are introduced into a simple molecular system (nBu4N)3M(NO3)x(SCN)y (nBu4N=tetrabutyl ammonium, M=rare‐earth metal, nBu=CH3CH2CH2CH2), and two new multifunctional molecular ferroelectrics are obtained: (nBu4N)3Nd(NO3)4(SCN)2 (1) and (nBu4N)3Pr(NO3)4(SCN)2 (2). Their distinct heat and dielectric anomaly dependence on temperature verifies that compounds 1 and 2 experience high‐temperature para‐ferroelectric phase transitions at 408 and 413 K, respectively. Strikingly, both molecular ferroelectrics possess large spontaneous polarization with Ps values of 9.05 and 8.50 μC cm−2, respectively, and are further characterized by the appearance of multiple intersecting non‐180° domains and polarization switching behavior. In particular, compounds 1 and 2 show good stability with only a small decrease in SHG intensity after switching cycles, suggesting that they have great potential for application in nonlinear optical (NLO) switches. Simultaneously, the rare‐earth compounds 1 and 2 present bright yellow–red and bright green fluorescence, respectively, at room temperature.
Multifunctional ferroelectrics: Two rare‐earth metal molecular ferroelectrics are synthesized: (nBu4N)3M(NO3)x(SCN)y (M=Nd, Pr). The two compounds have strong on–off second harmonic generation effects, and fluorescence characteristics that are adjustable from bright yellow–red to green light simply by changing the rare‐earth ion. These novel multifunctional molecular ferroelectric materials are promising for future applications.
The antitumor efficacy of Chinese herbal medicines has been widely recognized. Leading compounds such as sterols, glycosides, flavonoids, alkaloids, terpenoids, phenylpropanoids, and polyketides ...constitute their complex active components. The antitumor monomers derived from Chinese medicine possess an attractive anticancer activity. However, their use was limited by low bioavailability, significant toxicity, and side effects, hindering their clinical applications. Recently, new chemical entities have been designed and synthesized by combining natural drugs with other small drug molecules or active moieties to improve the antitumor activity and selectivity, and reduce side effects. Such a novel conjugated drug that can interact with several vital biological targets in cells may have a more significant or synergistic anticancer activity than a single‐molecule drug. In addition, antitumor conjugates could be obtained by combining pharmacophores containing two or more known drugs or leading compounds. Based on these studies, the new drug research and development could be greatly shortened. This study reviews the research progress of conjugates with antitumor activity based on Chinese herbal medicine. It is expected to serve as a valuable reference to antitumor drug research and clinical application of traditional Chinese medicine.
Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET), play key roles in drug discovery and development. A high-quality drug candidate should not only have sufficient ...efficacy against the therapeutic target, but also show appropriate ADMET properties at a therapeutic dose. A lot of
models are hence developed for prediction of chemical ADMET properties. However, it is still not easy to evaluate the drug-likeness of compounds in terms of so many ADMET properties. In this study, we proposed a scoring function named the ADMET-score to evaluate drug-likeness of a compound. The scoring function was defined on the basis of 18 ADMET properties predicted
our web server admetSAR. The weight of each property in the ADMET-score was determined by three parameters: the accuracy rate of the model, the importance of the endpoint in the process of pharmacokinetics, and the usefulness index. The FDA-approved drugs from DrugBank, the small molecules from ChEMBL and the old drugs withdrawn from the market due to safety concerns were used to evaluate the performance of the ADMET-score. The indices of the arithmetic mean and
-value showed that the ADMET-score among the three data sets differed significantly. Furthermore, we learned that there was no obvious linear correlation between the ADMET-score and QED (quantitative estimate of drug-likeness). These results suggested that the ADMET-score would be a comprehensive index to evaluate chemical drug-likeness, and might be helpful for users to select appropriate drug candidates for further development.
One dimensional (1D) organic‐inorganic halide hybrid perovskites have the advantages of excellent organic cation modifiability and diversity of inorganic framework structures, which cannot be ignored ...in the development of multi‐functional phase‐transition materials in photoelectric and photovoltaic devices. Here, we have successfully modified and synthesized an organic‐inorganic hybrid perovskite photoelectric multifunctional phase‐transition material: C7H13ONCH2F⋅PbBr3 (1). The synergistic effect of the order double disorder transition of organic cations and the change of the degree of distortion of the inorganic framework leads to its high temperature reversible phase‐transition point of Tc=374 K/346 K and its ultra‐low loss high‐quality dielectric switch response. Through in‐depth research and calculation, compound 1 also has excellent semiconductor characteristics with a band gap of 3.06 eV and the photoluminescence characteristics of self‐trapped exciton (STE) broadband emission. Undoubtedly, this modification strategy provides a new choice for the research field of organic‐inorganic hybrid perovskite reversible phase‐transition photoelectric multifunctional materials with rich coupling properties.
An organic‐inorganic hybrid perovskite photoelectric multifunctional material: C7H13ONCH2F PbBr3 (1) was successfully designed and synthesised. It realized the coupling of thermo‐dielectric switching characteristics, semiconductor characteristics and photoluminescence characteristics of STE broadband emission.
Organic‐inorganic hybrid multifunctional materials have shown significant application in lighting and sensor fields, owing to their prominent performance and diversity structures. Herein, we ...synthesized two multifunctional compounds: (propyl‐quinuclidone)2CdBr4 (1) and (F‐butyl‐quinuclidone)2CdBr4 (2). By introducing light‐emitting organic cation with flexible long chain, 1 and 2 exhibit excellent transition properties and bright blue‐white fluorescence. Then, combine fluorescence lifetime and first‐principal calculation, providing evidence for the electron transfer emission. Subsequently, investigated the impact of substituent carbon chain length (methyl to butyl), structural rigidity (C−C to C−F) and halide framework (Cl to I) on the fluorescence properties. Results indicate that Cd⋅⋅⋅Cd distance and structural rigidity play an important role in fluorescence. Overall, our research provides valuable insight and example for chemical modifications enhance compound performance.
Two Cd‐based hybrid multifunctional compounds with dual‐stable behavior in dielectric, high transition temperature and bright fluorescence were reported. Then, investigated the impact of substituent carbon chain length (methyl to butyl), structural rigidity (C−C to C−F), and halide framework (Cl to I) on fluorescent properties.
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