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.
Memory plays a vital role in modern information society. High‐speed and low‐power nonvolatile memory is urgently demanded in the era of big data. However, ultrafast nonvolatile memory with ...nanosecond‐timescale operation speed and long‐term retention is still unavailable. Herein, an ultrafast nonvolatile memory based on van der Waals heterostructure is proposed, where a charge‐trapping material, graphdiyne (GDY), serves as the charge‐trapping layer. With the band‐engineered heterostructure and excellent charge‐trapping capability of GDY, charges are directly injected into the GDY layer and are persistently captured by the trapping sites in GDY, which result in an ultrafast writing speed (8 ns), a low operation voltage (30 mV), and a long retention time (over 104 s). Moreover, a high on/off ratio of 106 is demonstrated by this memory, which enables the achievement of multibit storage with 6 discrete storage levels. This device fills the blank of ultrafast nonvolatile memory technology, which makes it a promising candidate for next‐generation high‐speed and low‐power‐consumption nonvolatile memory.
A novel semi‐floating‐gate nonvolatile memory based on van der Waals heterostructure is proposed, which combines the advantages of ultrafast writing speed (8 ns), low operation voltage (2–30 mV), long retention time (over 104 s), and high on/off ratio (106). This memory device fills the blank of ultrafast nonvolatile memory technology.
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.
Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with high incidence in both advanced and developing countries. Children surviving from HIE often have severe long-term sequela ...including cerebral palsy, epilepsy, and cognitive disabilities. The severity of HIE in infants is tightly associated with increased IL-1β expression and astrocyte activation which was regulated by transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel in the TRP family.
Neonatal hypoxic ischemia (HI) and oxygen-glucose deprivation (OGD) were used to simulate HIE in vivo and in vitro. Primarily cultured astrocytes were used for investigating the expression of glial fibrillary acidic protein (GFAP), IL-1β, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and activation of the nucleotide-binding, oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome by using Western blot, q-PCR, and immunofluorescence. Brain atrophy, infarct size, and neurobehavioral disorders were evaluated by Nissl staining, 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and neurobehavioral tests (geotaxis reflex, cliff aversion reaction, and grip test) individually.
Astrocytes were overactivated after neonatal HI and OGD challenge. The number of activated astrocytes, the expression level of IL-1β, brain atrophy, and shrinking infarct size were all downregulated in TRPV1 KO mice. TRPV1 deficiency in astrocytes attenuated the expression of GFAP and IL-1β by reducing phosphorylation of JAK2 and STAT3. Meanwhile, IL-1β release was significantly reduced in TRPV1 deficiency astrocytes by inhibiting activation of NLRP3 inflammasome. Additionally, neonatal HI-induced neurobehavioral disorders were significantly improved in the TRPV1 KO mice.
TRPV1 promotes activation of astrocytes and release of astrocyte-derived IL-1β mainly via JAK2-STAT3 signaling and activation of the NLRP3 inflammasome. Our findings provide mechanistic insights into TRPV1-mediated brain damage and neurobehavioral disorders caused by neonatal HI and potentially identify astrocytic TRPV1 as a novel therapeutic target for treating HIE in the subacute stages (24 h).
The neonatal heart possesses the ability to proliferate and the capacity to regenerate after injury; however, the mechanisms underlying these processes are not fully understood. Melatonin has been ...shown to protect the heart against myocardial injury through mitigating oxidative stress, reducing apoptosis, inhibiting mitochondrial fission, etc. In this study, we investigated whether melatonin regulated cardiomyocyte proliferation and promoted cardiac repair in mice with myocardial infarction (MI), which was induced by ligation of the left anterior descending coronary artery. We showed that melatonin administration significantly improved the cardiac functions accompanied by markedly enhanced cardiomyocyte proliferation in MI mice. In neonatal mouse cardiomyocytes, treatment with melatonin (1 μM) greatly suppressed miR-143-3p levels. Silencing of miR-143-3p stimulated cardiomyocytes to re-enter the cell cycle. On the contrary, overexpression of miR-143-3p inhibited the mitosis of cardiomyocytes and abrogated cardiomyocyte mitosis induced by exposure to melatonin. Moreover, Yap and Ctnnd1 were identified as the target genes of miR-143-3p. In cardiomyocytes, inhibition of miR-143-3p increased the protein expression of Yap and Ctnnd1. Melatonin treatment also enhanced Yap and Ctnnd1 protein levels. Furthermore, Yap siRNA and Ctnnd1 siRNA attenuated melatonin-induced cell cycle re-entry of cardiomyocytes. We showed that the effect of melatonin on cardiomyocyte proliferation and cardiac regeneration was impeded by the melatonin receptor inhibitor luzindole. Silencing miR-143-3p abrogated the inhibition of luzindole on cardiomyocyte proliferation. In addition, both MT1 and MT2 siRNA could cancel the beneficial effects of melatonin on cardiomyocyte proliferation. Collectively, the results suggest that melatonin induces cardiomyocyte proliferation and heart regeneration after MI by regulating the miR-143-3p/Yap/Ctnnd1 signaling pathway, providing a new therapeutic strategy for cardiac regeneration.
Artificial synapses and neurons are crucial milestones for neuromorphic computing hardware, and memristors with resistive and threshold switching characteristics are regarded as the most promising ...candidates for the construction of hardware neural networks. However, most of the memristors can only operate in one mode, that is, resistive switching or threshold switching, and distinct memristors are required to construct fully memristive neuromorphic computing hardware, making it more complex for the fabrication and integration of the hardware. Herein, we propose a flexible dual‐mode memristor array based on core–shell CsPbBr3@graphdiyne nanocrystals, which features a 100% transition yield, small cycle‐to‐cycle and device‐to‐device variability, excellent flexibility, and environmental stability. Based on this dual‐mode memristor, homo‐material‐based fully memristive neuromorphic computing hardware—a power‐free artificial nociceptive signal processing system and a spiking neural network—are constructed for the first time. Our dual‐mode memristors greatly simplify the fabrication and integration of fully memristive neuromorphic systems.
An optically modulated dual‐mode memristor array based on core–shell CsPbBr3@graphdiyne nanocrystals is developed, which can emulate both the artificial synapses and neurons. Based on this dual‐mode memristor, homo‐material‐based fully memristive neuromorphic computing hardware including a power‐free artificial nociceptive signal processing system and a spiking neural network are constructed for the first time.
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.
Polygonatum rhizoma polysaccharide (PP) is a main ingredient of Polygonatumrhizoma, which is both food and traditional herbal medicine. In this study, we aimed to investigate the hypoglycemic effect ...of PP and the underlying mechanisms in db/db mice. Our finding showed that PP significantly ameliorates diabetic symptoms by reducing glucose levels in blood and urine and increasing insulin and leptin abundance in the serum. Histopathological examination revealed that PP improved the pathological state and increased hepatic glycogen storage in liver. Additionally, RT-qPCR results indicated that PP significantly down-regulated the expression of phosphoenolpyruvate carboxykinase 1. Furthermore, 16s rRNA sequencing results demonstrated that PP intervention resulted in an increase in beneficial bacteria genus and a reduction in harmful genus. Redundancy analysis revealed the correlation between intestinal flora and clinical factors. Taken together, these results suggest that PP has a significant hypoglycemic effect on type 2 diabetes (T2D) through up-regulating serum insulin and leptin, as well as hepatic glycogen storage, and down-regulating hepatic phosphoenolpyruvate carboxykinase 1 expression, as well as modulating gut microbiota composition. In conclusion, this study investigated the mechanisms of PP in the treatment of diabetes in db/db mice. To the best of our knowledge, this is the first study to explore the positive and negative correlations between gut microbiota and clinical factors, such as oxidative stress injury in liver and glucose related indicators in the blood.
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AIM： To observe the attenuation of ethanol extract of Herba Scutellaria barbata （SE） against diabetic retinopathy （DR） and its engaged mechanism. METHODS： C57BL/6J mice were intraperitoneally ...injected with streptozotocin （STZ, 55 mg/kg） for 5 consecutive days to induce diabetes, The diabetic mice were orally given with SE （100, 200 mg/kg） for lmo at lmo after STZ injection. Blood-retinal barrier （BRB） breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction （RT-PCR）, Western blot and immunofiuorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum contents of tumor necrosis factor-e （TNF-a） and interleukin （IL）-II. RESULTS： SE （100, 200 mg/kg） reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction （T J） proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-a and IL-113. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 （ICAM-1）. SE reduced the increased phosphorylation of nuclear factor kappa B （NFKB） p65 and its subsequent nuclear translocation in retinas from STZ- induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 （Ibal） demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION： SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high vascularity and frequent metastasis. Tumor-associated abnormal vasculature was reported to accelerate TNBC ...metastasis. Scutellarin (SC) is a natural flavonoid with a cardiovascular protective function. In this study, SC reduced TNBC metastasis and alleviated tumor-associated vascular endothelial barrier injury in vivo. SC rescued the tumor necrosis factor-α (TNFα)-induced diminishment of endothelial junctional proteins and dysfunction of the endothelial barrier in vitro. SC reduced the increased transendothelial migration of TNBC cells through a monolayer composed of TNFα-stimulated human mammary microvascular endothelial cells (HMMECs) or human umbilical vein endothelial cells (HUVECs). TNFα induced the nuclear translocation of enhancer of zeste homolog-2 (EZH2), and its chemical inhibitor GSK126 blocked TNFα-induced endothelial barrier disruption and subsequent TNBC transendothelial migration. TNF receptor 2 (TNFR2) is the main receptor by which TNFα regulates endothelial barrier breakdown. Extracellular signal-regulated protein kinase (ERK)1/2 was found to be downstream of TNFα/TNFR2 and upstream of EZH2. Additionally, SC abrogated the TNFR2-ERK1/2-EZH2 signaling axis both in vivo and in vitro. Our results suggest that SC reduced TNBC metastasis by suppressing TNFα-initiated vascular endothelial barrier breakdown through rescuing the reduced expression of junctional proteins by regulating the TNFR2-ERK1/2-EZH2 signaling pathway.
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