Artificial synapses are the key building blocks for low‐power neuromorphic computing that can go beyond the constraints of von Neumann architecture. In comparison with two‐terminal memristors and ...three‐terminal transistors with filament‐formation and charge‐trapping mechanisms, emerging electrolyte‐gated transistors (EGTs) have been demonstrated as a promising candidate for neuromorphic applications due to their prominent analog switching performance. Here, a novel graphdiyne (GDY)/MoS2‐based EGT is proposed, where an ion‐storage layer (GDY) is adopted to EGTs for the first time. Benefitting from this Li‐ion‐storage layer, the GDY/MoS2‐based EGT features a robust stability (variation < 1% for over 2000 cycles), an ultralow energy consumption (50 aJ µm−2), and long retention characteristics (>104 s). In addition, a quasi‐linear conductance update with low noise (1.3%), an ultrahigh Gmax/Gmin ratio (103), and an ultralow readout conductance (<10 nS) have been demonstrated by this device, enabling the implementation of the neuromorphic computing with near‐ideal accuracies. Moreover, the non‐volatile characteristics of the GDY/MoS2‐based EGT enable it to demonstrate logic‐in‐memory functions, which can execute logic processing and store logic results in a single device. These results highlight the potential of the GDY/MoS2‐based EGT for next‐generation low‐power electronics beyond von Neumann architecture.
A novel graphdiyne (GDY)/MoS2‐based electrolyte‐gated transistor using GDY as a Li‐ion‐storage layer is proposed, which features robust stability and flexibility, an ultralow energy consumption, a long retention time, a quasi‐linear weight update with low noise, an ultrahigh Gmax/Gmin ratio, and an ultralow readout conductance. This GDY/MoS2‐based EGT has demonstrated its potential in applications of neuromorphic computing and in‐memory computing.
Previous studies report that (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic ingredient in green tea, has high efficacy against Alzheimer's disease (AD) in various in vivo and ...in vitro models. However, as a water-soluble component, how EGCG exerts its anti-AD effects in the brain was not elucidated. In the present study, we investigated the anti-AD mechanisms of EGCG in natural aging rats with cognitive impairments (CIs) assessed using Morris water maze. The rats were treated with EGCG (100 mg/kg per day, intragastrically) for 4 weeks. The expression of β-amyloid (Aβ
) in the brain was detected with immunohistochemical staining. We showed that EGCG administration significantly ameliorated the CI in the aging rats with CI and decreased Aβ
plaque formation in their brains. Then we used an efficient ultra-performance liquid chromatography-tandem mass spectrometer method to evaluate EGCG concentrations in rat plasma and tissue distribution. We found that EGCG absorption was significantly increased in the aging with CI group compared with control young rats. After oral administration of EGCG (100 mg), EGCG could not be detected in the brain tissues of control young rats, but it was found in the brain tissue of aging rats with CI. By using Evans Blue assay, transmission electron microscopy, and Western blotting assay, we demonstrated that the permeability of blood-brain barrier (BBB) was significantly increased in aging rats with CI. These results suggest that the permeability change of BBB is the physiological structural basis for EGCG treatment to improve learning and memory, thus providing a solid evidence for EGCG druggability in anti-AD therapeutic field.
Optoelectronic synapses integrating synaptic and optical-sensing functions exhibit large advantages in neuromorphic computing for visual information processing and complex learning, recognition, and ...memory in an energy-efficient way. However, electric stimulation is still essential for existing optoelectronic synapses to realize bidirectional weight-updating, restricting the processing speed, bandwidth, and integration density of the devices. Herein, a two-terminal optical synapse based on a wafer-scale pyrenyl graphdiyne/graphene/PbS quantum dot heterostructure is proposed that can emulate both the excitatory and inhibitory synaptic behaviors in an optical pathway. The simple device architecture and low-dimensional features of the heterostructure endow the optical synapse with robust flexibility for wearable electronics. This optical synapse features a linear and symmetric conductance-update trajectory with numerous conductance states and low noise, which facilitates the demonstration of accurate and effective pattern recognition with a strong fault-tolerant capability even at bending states. A series of logic functions and associative learning capabilities have been demonstrated by the optical synapses in optical pathways, significantly enhancing the information processing capability for neuromorphic computing. Moreover, an integrated visible information sensing memory processing system based on the optical synapse array is constructed to perform real-time detection, in situ image memorization, and distinction tasks. This work is an important step toward the development of optogenetics-inspired neuromorphic computing and adaptive parallel processing networks for wearable electronics.
Hepatocellular carcinoma (HCC) is one of the most lethal tumours worldwide. However, the effects of first-line sorafenib treatment in advanced HCC fail to prolong patients' survival due to the highly ...heterogeneous characteristics of HCC etiology. Cyclin-dependent kinase 9 (CDK9) is an important target in the continuous development of cancer therapy. Here, we demonstrate that CDK9 is closely associated with the progression of HCC and can serve as an HCC therapeutic target by modulating the recovery of wild-type p53 (wt-p53) function. We prove that mouse double minute 2 homologue (MDM2) and Sirtuin 1 (SIRT1) are phosphorylated by CDK9 at Ser166 and Ser47, respectively. Inhibition of CDK9 not only reduces the MDM2-mediated ubiquitination and degradation of wt-p53 but also increases wt-p53 stability by suppressing deacetylase activity of SIRT1. Thus, inhibition of CDK9 promotes the wt-p53 stabilization and prevents HCC progression. However, excessive inhibition by high concentrations of specific CDK9 inhibitors counteracts the promotion of p53 stability and reduces their anti-HCC activity because of extreme general transcription repression. The effects of a novel CDK9 inhibitor named oroxylin A (OA) from Scutellaria baicalensis are explored, with the results indicating that OA shows moderate and controlled inhibition of CDK9 activity and expression, and stabilizes wt-p53 by inhibiting CDK9-regulated MDM2 and SIRT1 signaling. These outcomes indicate the high therapeutic potential of OA against HCC and its low toxicity in normal tissue. This study demonstrates a novel mechanism for the regulation of wt-p53 by CDK9 and indicates that OA is a potential candidate for HCC therapy.
Achieving multifunctional van der Waals nanoelectronic devices on one structure is essential for the integration of 2D materials; however, it involves complex architectural designs and manufacturing ...processes. Herein, a facile, fast, and versatile laser direct write micro/nanoprocessing to fabricate diode, NPN (PNP) bipolar junction transistor (BJT) simultaneously based on a pre‐fabricated black phosphorus/molybdenum disulfide heterostructure is demonstrated. The PN junctions exhibit good diode rectification behavior. Due to different carrier concentrations of BP and MoS2, the NPN BJT, with a narrower base width, renders better performance than the PNP BJT. Furthermore, the current gain can be modulated efficiently through laser writing tunable base width WB, which is consistent with the theoretical results. The maximum gain for NPN and PNP is found to be ≈41 (@WB≈600 nm) and ≈12 (@WB≈600 nm), respectively. In addition, this laser write processing technique also can be utilized to realize multifunctional WSe2/MoS2 heterostructure device. The current work demonstrates a novel, cost‐effective, and universal method to fabricate multifunctional nanoelectronic devices. The proposed approach exhibits promise for large‐scale integrated circuits based on 2D heterostructures.
Herein, a facile, fast, and versatile laser direct write micro/nanoprocessing technique is utilized to achieve multifunctional nanoelectronic devices (PN diode, NPN, and PNP bipolar junction transistor (BJT)) simultaneously based on one 2D material heterostructure. The current gain of the BJT can be modulated efficiently by the laser writing tunable base width.
Graphdiyne (GDY) is emerging as a promising material for various applications owing to its unique structure and fascinating properties. However, the application of GDY in electronics and ...optoelectronics are still in its infancy, primarily owing to the huge challenge in the synthesis of large-area and uniform GDY film for scalable applications. Here a modified van der Waals epitaxy strategy is proposed to synthesize wafer-scale GDY film with high uniformity and controllable thickness directly on graphene (Gr) surface, providing an ideal platform to construct large-scale GDY/Gr-based optoelectronic synapse array. Essential synaptic behaviors have been realized, and the linear and symmetric conductance-update characteristics facilitate the implementation of neuromorphic computing for image recognition with high accuracy and strong fault tolerance. Logic functions including “NAND” and “NOR” are integrated into the synapse which can be executed in an optical pathway. Moreover, a visible information sensing-memory-processing system is constructed to execute real-time image acquisition,
in situ
image memorization and distinction tasks, avoiding the time latency and energy consumption caused by data conversion and transmission in conventional visual systems. These results highlight the potential of GDY in applications of neuromorphic computing and artificial visual systems.
Intracellular Staphylococcus aureus (S. aureus) often causes clinical failure and relapse after antibiotic treatment. We previously found that 20(S)-ginsenoside Rh2 20(S)-Rh2 enhanced the therapeutic ...effect of quinolones in a mouse model of peritonitis, which we attributed to the increased concentrations of quinolones within bacteria. In this study, we investigated the enhancing effect of 20(S)-Rh2 on levofloxacin (LVF) from a perspective of intracellular bacteria. In S. aureus 25923-infected mice, coadministration of LVF (1.5 mg/kg, i.v.) and 20(S)-Rh2 (25, 50 mg/kg, i.g.) markedly increased the survival rate, and decreased intracellular bacteria counts accompanied by increased accumulation of LVF in peritoneal macrophages. In addition, 20(S)-Rh2 (1, 5, 10 μM) dose-dependently increased the uptake and accumulation of LVF in peritoneal macrophages from infected mice without drug treatment. In a model of S. aureus 25923-infected THP-1 macrophages, we showed that 20(S)-Rh2 (1, 5, 10 μM) dose-dependently enhanced the intracellular antibacterial activity of LVF. At the cellular level, 20(S)-Rh2 increased the intracellular accumulation of LVF by inhibiting P-gp and BCRP. PK-PD modeling revealed that 20(S)-Rh2 altered the properties of the cell but not LVF. At the subcellular level, 20(S)-Rh2 did not increase the distribution of LVF in lysosomes but exhibited a stronger sensitizing effect in acidic environments. Molecular dynamics (MD) simulations showed that 20(S)-Rh2 improved the stability of the DNA gyrase-LVF complex in lysosome-like acidic conditions. In conclusion, 20(S)-Rh2 promotes the cellular pharmacokinetics and intracellular antibacterial activities of LVF against S. aureus through efflux transporter inhibition and subcellular stabilization, which is beneficial for infection treatment.
It is an indisputable fact that electrochemical performance is always ameliorated by introducing proper phosphorus vacancy defect into electrode materials. In this work, the lattice-like CoP grown on ...the nickel foam with appropriate concentration of vacancies is fabricated successfully. The specific capacitance of 1865 F g−1 is improved by 1.7 times compared with the pristine CoP of 1125 F g−1 at the current density of 1 A g−1. Meanwhile, the deliberately designed electrode also possesses great stability of retention rate up to 90% after 5000 cycles. Before the electrode is assembled into the asymmetric supercapacitor, the potential window is altered by electrode potential blend technique in order to utilize capacitances of anode and cathode efficiently. Subsequently, the supercapacitor is studied in the electrochemistry systematically. The results show that power density is up to 737 W kg−1 as energy density is 31 W h kg−1. Meanwhile, the capacitance retention rate remains 88% after 5000 cycles. It is a meaningful guide for exploring efficient energy storage equipment that appropriate vacancies are injected into electrode materials, and optimal potential windows are obtained via electrode potential blend technology.
The self-supported CoP with lattice-like morphology was prepared on the nickel foam homogeneously. Subsequently, the as-prepared samples, under the circumstances of Ar plasma, were introduced phosphorus vacancies into for different time. On the basis of electrochemical measurement and analysis of the related samples, the sample bombarded in the plasma for 15 min marked as 15-CoP@NF owns optimal performances. Afterwards, before being assembled as supercapacitor, the potential windows of the 15-CoP@NF and CMK-3@NF were adjusted via charge injection method. Finally, the as-assembled supercapacitor was investigated in the electrochemical properties showing more excellent performance than the original in every aspect. It is a new guide for researchers to study electrochemical energy storage equipment with high performance. Display omitted
•The self-supported CoP is successfully prepared on nickel foam via modifying technological parameters.•The CoP@NF with optimal vacancy concentration is fabricated for supercapacitor via adopting magnetron sputtering technique.•The 15-CoP//CMK-3 is assembled via electrode potential blend technology and shows marked pseudocapacitive performance.
Emerging observational studies suggest an association between metabolic syndrome (MetS) and osteoarthritis (OA). This meta-analysis was conducted to examine whether or not there is a bidirectional ...relationship between MetS and OA.
The PubMed and Embase databases were searched from their inception to October 2019. We selected studies according to predefined criteria. Random effects were selected to calculate two sets of pooled risk estimates: MetS predicting OA and OA predicting MetS.
A total of seven cross-sectional studies and four cohort studies met the criteria for MetS predicting the onset of OA. Another six cross-sectional studies and one cohort study met the criteria for OA predicting the onset of MetS. The pooled odds risk (OR) for OA incidences associated with baseline MetS was 1.45 (95% CI 1.27-1.66). The OR for MetS incidences associated with baseline OA was 1.90 (95% CI 1.11-3.27). In an overall analysis, we found that MetS was associated with prevalent OA in both cross-sectional studies (OR = 1.32, 95% CI 1.21-1.44) and cohort studies (OR = 1.76, 95% CI 1.29-2.42). No indication of heterogeneity was found in the cross-sectional studies (p = 0.395, I
= 4.8%), whereas substantial heterogeneity was detected in the cohort studies (p = 0.000, I
= 79.3%).
Meta-analysis indicated a bidirectional association between MetS and OA. We advise that patients with MetS should monitor their OA status early and carefully, and vice versa.
This work successfully synthesized blue-fluorescence and photostability manganese-doped carbon dots (Mn-CDs). The Mn-CDs are demonstrated as promising fluorescent sensors for Fe3+, indicating their ...great potential as a fluorescent probe for chemical sensing.
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Heteroatom doped carbon dots (CDs) with distinct merits are of great attractions in various fields such as solar cells, catalysis, trace element detection and photothermal therapy. In this work, we successfully synthesized blue-fluorescence and photostability manganese-doped carbon dots (Mn-CDs) with a quantum yield up to 7.5%, which was prepared by a facile one-step hydrothermal method with sodium citrate and manganese chloride. The Mn-CDs is the high mono-dispersity, uniform spherical nanoparticles. The Mn element plays a critical role in achieving a high quantum yield in synthesis of carbon dots, which was confirmed by the structure analysis using XPS and FTIR. Spectroscopic investigations proved that the decent PLQY and luminescence properties of Mn-CDs are due to the heteroatom doped, oxidized carbon-based surface passivation. In addition, the Mn-CDs are demonstrated as promising fluorescent sensors for iron ions with a linear range of 0–500 μmol/L and a detection limit of 2.1 nmol/L (turn-off), indicating their great potential as a fluorescent probe for chemical sensing.
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