Exosomes are nanosized extracellular vesicles (EVs) that show great promise in tissue regeneration and injury repair as mesenchymal stem cell (MSC). MSC has been shown to alleviate diabetes mellitus (DM) in both animal models and clinical trials. In this study, we aimed to investigate whether exosomes from human umbilical cord MSC (hucMSC-ex) have a therapeutic effect on type 2 DM (T2DM). We established a rat model of T2DM using a high-fat diet and streptozotocin (STZ). We found that the intravenous injection of hucMSC-ex reduced blood glucose levels as a main paracrine approach of MSC. HucMSC-ex partially reversed insulin resistance in T2DM indirectly to accelerate glucose metabolism. HucMSC-ex restored the phosphorylation (tyrosine site) of the insulin receptor substrate 1 and protein kinase B in T2DM, promoted expression and membrane translocation of glucose transporter 4 in muscle, and increased storage of glycogen in the liver to maintain glucose homeostasis. HucMSC-ex inhibited STZ-induced β-cell apoptosis to restore the insulin-secreting function of T2DM. Taken together, exosomes from hucMSC can alleviate T2DM by reversing peripheral insulin resistance and relieving β-cell destruction, providing an alternative approach for T2DM treatment.
Memtransistor is a multiterminal device combining the concepts of memristor and field-effect transistor with two-dimensional (2D) materials. The gate tunability of resistive switching in 2D memtransistor enables the multifunctional modulation and promising applications in neuromorphic network. However, the tunability of switching ratio in 2D memtransistor remains small and seriously limits its practical application. Here, we investigate a memtransistor based on a 3-layer MoS2 and realize the electric, light, and their combined modulations. In the electric gate mode, switching ratio is tunable in a large scale in the range 100–105. In the light gate mode, a maximum conductance change of 450% can be obtained by increasing the light power. Moreover, the switching ratio can be further improved to ∼106 through a combination of electric and light dual gating. Such a gating effect can be ascribed to the modulation of carrier density in the MoS2 channel. Our work provides a simple approach for achieving a high-performance multifunctional memtransistor.
Exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Ex) have been suggested as novel nanomaterials for regenerative medicine. Here we explored the roles of hucMSC-Ex through regulating Yes-associated protein (YAP) in renal injury repair by using rat unilateral ureteral obstruction (UUO) models. Our study identified mechanical stress induced YAP nucleus expression and stimulated collagen deposition and interstitial fibrosis in the kidney. Then, infusion with hucMSC-Ex promoted YAP nuclear cytoplasmic shuttling and ameliorated renal fibrosis in UUO model. Interestingly, hucMSC-Ex delivered casein kinase 1δ (CK1δ) and E3 ubiquitin ligase β-TRCP to boost YAP ubiquitination and degradation. Knockdown of CK1δ and β-TRCP in hucMSC decreased the repairing effects of hucMSC-Ex on renal fibrosis. Our results suggest that hucMSC-Ex attenuates renal fibrosis through CK1δ/β-TRCP inhibited YAP activity, unveiling a new mechanism for the therapeutic effects of hucMSC-Ex on tissue injury and offering a potential approach for renal fibrosis treatment.
Electrochemical metallization memories (ECM)-based memristors are widely regarded as potential electronic devices for neuromorphic computing. However, in ECM-based memristors, the formation of metallic conducting filament in insulating layer will cause an abrupt current increase, making it hard for analog neuromorphic emulation. Here, a memristor fabricated by using two-dimensional (2D) semiconductor MoS 2 that can provide atomically smooth and semi-insulating surface as the medium for electric-field-driven migration of conducting filaments is proposed. This memristor based on the Ag ions migration on 2D MoS 2 surface exhibits gradual conductance change behavior. Microstructure characterization shows that such gradual conductance change behavior can be attributed to the formation of conducting filament composed of a chain of metallic Ag nanoparticles of %5 nm at ONstate device. By comparing with biological experimental data, it is found that our device can well mimic the learning behavior of Drosophila. Finding shows the potential to realize stable analog ECM-based memristors and paves the way for fabricating large-scale memristor network.
In most cases, the current flows uniformly through the device in the HRS and is restricted to a local region with high conductance known as a conducting filament (CF) in the LRS. [3] Among them, a specific memory device is termed as conductivebridge RRAM (CBRAM), where the formation/rupture of metallic conductive filaments are dominated by cation migration and redox processes. [4] Meanwhile, volatile resistance switching behaviors are commonly observed in CBRAM as threshold switching (TS). Analogous to the nonvolatile electrochemical metallization mechanism in terms of materials and structures, [5] the electrical resistance of such a threshold switching memristor (TSM) could decrease by orders of magnitude when an electric field is applied due to the formation of CFs with active metal (such as Ag or Cu) atoms. [6] Differently, the resistance returns back spontaneously after the termination of the external bias, yielding a superior I-V nonlinearity and unique temporal conductance evolution dynamics. [7] Recent years, the threshold switching memristors based on active metals are also called "diffusive memristors" to emphasize the diffusion dynamics of the metal species. [8] To be more comprehensively, redox-diffusive threshold switching memristor (RDTSM) might be the best choice to demonstrate the overall switching behavior. [1a] RDTSM has gained significant attention due to its similar advantages to RRAM, such as the simple structure, great fabricability and integrability, and compatibility with conventional CMOS technology. More importantly, it has great potential in many vital applications, such as two-terminal selectors with high nonlinearity, [9] high-powerefficient synaptic or neuronal devices with novel functions. [8,10] A specific application requires a correspondingly proper device. Figure 1 displays the measurement schematic of the key parameters of RDTSM, including selectivity (or nonlinearity), compliance currents, switching voltages (including threshold voltages and hold voltages),TS mode (unidirectional and bidirectional, as shown in Figure 1a,b, respectively), switching slopes (Figure 1c), response time (including delay and relaxation, as shown in Figure 1d) and endurance, which are all up to the material composition and device structure. [11] Therefore, With the rapid development of information technique in the big-data era, there is an extremely urgent demand for new circuit building blocks, represented by resistive switching memristors with high speed, high-density integration, and power-efficiency, to overcome the limitations of electronic device scaling and thus achieve non-von-Neumann neuromorphic computing. Redox-diffusive threshold switching memristors, based on the volatile formation/rupture of metallic conductive filaments, are attracting great attention for many novel applications, ranging from selectors to synaptic and neuronal devices. Here, how to design a proper redox-diffusive threshold switching memristor is comprehensively introduced, with particular focus on the effect of the devic...
Magnetic skyrmions are vortex-like spin textures with nontrivial spin topology and novel physical properties that show promise as an essential building block for novel spintronic applications. Skyrmions in synthetic antiferromagnets (SAF) have been proposed long-term to have many advantages than those in ferromagnetic materials, which suffer from fundamental limits for size and efficient manipulation. Thus, experimental realization of skyrmions in SAF is intensely pursued. Here we show the observation of zero-field stable magnetic skyrmions at room temperature in SAF [Co/Pd]/Ru/[Co/Pd] multilayers with Lorentz transmission electron microscope, where uncompensated moments of the SAF provide a medium for the skyrmion characterization. Isolated skyrmions and high-density skyrmions via magnetic field and electromagnetic coordinated methods have been observed, respectively. These created high-density skyrmions maintain at zero-field even when both the current and magnetic field are removed. The use of skyrmions in SAF would advance the process toward practical nonvolatile memories based on spin topology.
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