SummaryThe bisindole indirubin has been described, more than 30 years ago, as being clinically active in the treatment of human chronic myelocytic leukaemia. However, the underlying mechanism of action has remained unclear. We have reported previously that indirubin and its analogues are potent and selective inhibitors of cyclin-dependent kinases (CDK). In this study, we investigated the influence of indirubin and derivatives on CDK1/cyclin B kinase in human tumour cells at concentrations known to induce growth inhibition. Cells of the mammary carcinoma cell line MCF-7, synchronized by serum deprivation, after serum repletion stay arrested in the G 1 /G 0 phase of the cell cycle in the presence of 2 µM indirubin-3′-monoxime. At higher drug concentrations (≥ 5 µM) an increase of the cell population in the G 2 /M phase is additionally observed. Cells synchronized in G 2 /M phase by nocodazole remain arrested in the G 2 /M phase after release, in the presence of indirubin-3′-monoxime (≥5 µM). After 24 h treatment with 10 µM indirubin-3′-monoxime a sub-G 2 peak appears, indicative for the onset of apoptotic cell death. Treatment of MCF-7 cells with growth inhibitory concentrations of indirubin-3′-monoxime induces dose-dependent inhibition of the CDK1 activity in the cell. After 24 h treatment, a strong decrease of the CDK1 protein level along with a reduction of cyclin B in complex with CDK1 is observed. Taken together, the results of this study strongly suggest that inhibition of CDK activity in human tumour cells is a major mechanism by which indirubin derivatives exert their potent antitumour efficacy.

Modern-days CMOS-based computation technology is reaching fundamental limitations which restrain further progress towards faster and more energy efficient devices [1]. A promising path to overcome these limitations is the emerging field of magnonics which utilizes spin waves for data transport and computation operations [2-5]. Many different devices have already been demonstrated on the macro-and microscale [2,4-12]. However, the feasibility of this technology essentially relies on the scalability to the nanoscale and a proof that coherent spin waves can propagate in these structures.Here, we present a study of the spin-wave dynamics in individual yttrium iron garnet (YIG) magnonic conduits with lateral dimensions down to 50 nm. Space and time resolved micro-focused Brillouin-Light-Scattering (BLS) spectroscopy is used to extract the exchange constant and directly measure the spin-wave decay length and group velocity. Thereby, the first experimental proof of propagating spin waves in individual nano-sized YIG conduits and the fundamental feasibility of a nano-scaled magnonics are demonstrated.State of the art investigations are typically performed in micron-sized structures [13][14][15] lacking the final push to the nanoscale and are often based on the so-called Damon-Eshbach (DE) geometry, since this geometry provides a high spin-wave group velocity [16]. However, large bias magnetic fields are required to achieve the corresponding magnetization state in nano-sized conduits. Therefore, using the Backward-Volume (BV) geometry is a necessity regarding any application of spin waves for data processing, since it corresponds to the natural self-magnetized state of such a conduit. Besides the propagation geometry, the choice of material is crucial as well. Being the material providing the lowest known spin-wave damping, yttrium iron garnet (YIG) is the naturally preferred material for magnonics. However, this comes at the cost of a complex crystallographic structure [17] featuring a unit cell size of 1.2376 nm [18], which opens up the question whether the material can be scaled down to the nanoscale while preserving its unique properties during this process.Here, a thin (111) YIG film with a thickness of = 44 nm is used, which is grown on top of a 500 µm thick (111) Gadolinium Gallium Garnet (GGG) substrate by Liquid Phase Epitaxy (LPE) [19]. A preliminary characterization by stripline Vector-Network-Analyzer ferromagnetic resonance (VNA-FMR) spectroscopy [20,21] is performed to obtain the fundamental magnetic properties. The measurement, shown in Supplementary Fig. S1, yields a saturation magnetization of s = (140.7 ± 2.8) kA m and a Gilbert damping parameter of = (1.75 ± 0.08) × 10 −4 . These values are common for high-quality YIG thin films [19]. Thereafter, the nanostructuring process is carried out by Figure 2| Measurement of the thermal spin-wave population and determined exchange constant. (a) Exemplary thermal BLS spectra in the absence of any microwave excitation for a = 1000 YIG waveguide. A field dependent ...

Despite recent advances in exfoliated vdW ferromagnets, the widespread application of 2D magnetism requires a Curie temperature (Tc) above room temperature as well as a stable and controllable magnetic anisotropy. Here we demonstrate a large-scale iron-based vdW material Fe4GeTe2 with the Tc reaching ~530 K. We confirmed the high-temperature ferromagnetism by multiple characterizations. Theoretical calculations suggested that the interface-induced right shift of the localized states for unpaired Fe d electrons is the reason for the enhanced Tc, which was confirmed by ultraviolet photoelectron spectroscopy. Moreover, by precisely tailoring Fe concentration we achieved arbitrary control of magnetic anisotropy between out-of-plane and in-plane without inducing any phase disorders. Our finding sheds light on the high potential of Fe4GeTe2 in spintronics, which may open opportunities for room-temperature application of all-vdW spintronic devices.

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