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2.
Adv Mater ; : e1905764, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31850652

RESUMO

Neuromorphic computing consisting of artificial synapses and neural network algorithms provides a promising approach for overcoming the inherent limitations of current computing architecture. Developments in electronic devices that can accurately mimic the synaptic plasticity of biological synapses, have promoted the research boom of neuromorphic computing. It is reported that robust ferroelectric tunnel junctions can be employed to design high-performance electronic synapses. These devices show an excellent memristor function with many reproducible states (≈200) through gradual ferroelectric domain switching. Both short- and long-term plasticity can be emulated by finely tuning the applied pulse parameters in the electronic synapse. The analog conductance switching exhibits high linearity and symmetry with small switching variations. A simulated artificial neural network with supervised learning built from these synaptic devices exhibited high classification accuracy (96.4%) for the Mixed National Institute of Standards and Technology (MNIST) handwritten recognition data set.

3.
ACS Appl Mater Interfaces ; 11(46): 43473-43479, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31702891

RESUMO

The development of artificial synapses has enabled the establishment of brain-inspired computing systems, which provides a promising approach for overcoming the inherent limitations of current computer systems. The two-terminal memristors that faithfully mimic the function of biological synapses have intensive prospects in the neural network field. Here, we propose a high-performance artificial synapse based on oxide tunnel junctions with oxygen vacancy migration. Both short-term and long-term plasticities are mimicked in one device. The oxygen vacancy migration through oxide ultrathin films is utilized to manipulate long-term plasticity. Essential synaptic functions, such as paired pulse facilitation, post-tetanic potentiation, as well as spike-timing-dependent plasticity, are successfully implemented in one device by finely modifying the shape of the pre- and postsynaptic spikes. Ultralow femtojoule energy consumption comparable to that of the human brain indicates its potential application in efficient neuromorphic computing. Oxide tunnel junctions proposed in this work provide an alternative approach for realizing energy-efficient brain-like chips.

4.
iScience ; 16: 368-377, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31220760

RESUMO

Oxide-based resistive switching devices, including ferroelectric tunnel junctions and resistance random access memory, are promising candidates for the next-generation non-volatile memory technology. In this work, we propose a ferroionic tunnel junction to realize a giant electroresistance. It functions as a ferroelectric tunnel junction at low resistance state and as a Schottky junction at high resistance state, due to interface engineering through the field-induced migration of oxygen vacancies. An extremely large electroresistance with ON/OFF ratios of 5.1×107 at room temperature and 2.1×109 at 10 K is achieved, using an ultrathin BaTiO3-δ layer as the ferroelectric barrier and a semiconducting Nb-doped SrTiO3 substrate as the bottom electrode. The results point toward an appealing way for the design of high-performance resistive switching devices based on ultrathin oxide heterostructures by ionic controlled interface engineering.

5.
Adv Mater ; 31(19): e1900379, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30924206

RESUMO

Hardware implementation of artificial synaptic devices that emulate the functions of biological synapses is inspired by the biological neuromorphic system and has drawn considerable interest. Here, a three-terminal ferrite synaptic device based on a topotactic phase transition between crystalline phases is presented. The electrolyte-gating-controlled topotactic phase transformation between brownmillerite SrFeO2.5 and perovskite SrFeO3- δ is confirmed from the examination of the crystal and electronic structure. A synaptic transistor with electrolyte-gated ferrite films by harnessing gate-controllable multilevel conduction states, which originate from many distinct oxygen-deficient perovskite structures of SrFeOx induced by topotactic phase transformation, is successfully constructed. This three-terminal artificial synapse can mimic important synaptic functions, such as synaptic plasticity and spike-timing-dependent plasticity. Simulations of a neural network consisting of ferrite synaptic transistors indicate that the system offers high classification accuracy. These results provide insight into the potential application of advanced topotactic phase transformation materials for designing artificial synapses with high performance.

6.
J Exp Bot ; 70(12): 3089-3099, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30919902

RESUMO

Cuticular waxes, long-chain hydrocarbon compounds, form the outermost layer of plant surfaces in most terrestrial plants. The presence of cuticular waxes protects plants from water loss and other environmental stresses. Cloning and characterization of genes involved in the regulation, biosynthesis, and extracellular transport of cuticular waxes onto the surface of epidermal cells have revealed the molecular basis of cuticular wax accumulation. However, intracellular trafficking of synthesized waxes to the plasma membrane for cellular secretion is poorly understood. Here, we characterized a maize glossy (gl6) mutant that exhibited decreased epicuticular wax load, increased cuticle permeability, and reduced seedling drought tolerance relative to wild-type. We combined an RNA-sequencing-based mapping approach (BSR-Seq) and chromosome walking to identify the gl6 candidate gene, which was confirmed via the analysis of multiple independent mutant alleles. The gl6 gene represents a novel maize glossy gene containing a conserved, but uncharacterized, DUF538 domain. This study suggests that the GL6 protein may be involved in the intracellular trafficking of cuticular waxes, opening the door to elucidating the poorly understood process by which cuticular wax is transported from its site of biosynthesis to the plasma membrane.

7.
J Ethnopharmacol ; 235: 155-163, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30763696

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The abnormal increase in vascular smooth muscle cell (VSMC) proliferation and migration are critical events in the pathogenesis of cardiovascular diseases (CVDs) including restenosis and atherosclerosis. The dried roots of Scutellaria baicalensis Georgi (common name: Huangqin in China) have been confirmed to possess beneficial effects on CVD by clinical and modern pharmacological studies. Flavonoids in Huangqin exert anti-proliferative and anti-migratory effects. Similar to Huangqin, Scutellaria strigillosa Hemsley (SSH) has been used to clear heat and damp and is especially rich in flavonoids including wogonin, wogonoside, baicalein, and baicalin. However, there have been few of reports about pharmacological activities of SSH. AIM OF THE STUDY: To investigate the anti-proliferative and anti-migratory properties of Scutellaria strigillosa Hemsley extract (SSHE) in vitro and in vivo and explore its possible mechanism of action. MATERIALS AND METHODS: The chemical constituents of SSHE were analyzed by ultra-high performance liquid chromatography coupled with triple time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS). Cell proliferation and migration were investigated using BrdU incorporation assay and cell scratch test, respectively. The protein expression was determined by western blotting. In vivo, we established an artery ligation model of C57BL/6 mice and orally administered them with 50 or 100 mg/kg/day of SSHE. The carotid arteries were harvested and the intima-media thickness was examined 28 days post-ligation. RESULTS: Twelve compounds were identified and tentatively characterized. SSHE significantly inhibited the VSMC proliferation and migration stimulated by PDGF-BB and decreased the relative protein expression of regulatory signaling intermediates. Furthermore, the expression of SM22α was significantly elevated in SSHE-pretreated VSMCs, whereas knockdown of SM22α impaired the PDGF-BB-induced proliferation and migration arrest. Meanwhile, both ROS generation and the phosphorylation of ERK decreased in SSHE-pretreated VSMCs. In carotid artery ligation mice model, SSHE treatment significantly inhibited neointimal hyperplasia. CONCLUSIONS: SSHE significantly inhibited the PDGF-BB-induced VSMC proliferation, migration, and neointimal hyperplasia of carotid artery caused by ligation. Upregulation of SM22α expression, inhibition of ROS generation and ERK phosphorylation were, at least, partly responsible for the effects of SSHE on VSMCs.


Assuntos
Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Scutellaria/química , Animais , Becaplermina/administração & dosagem , Espessura Intima-Media Carotídea , Movimento Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Extratos Vegetais/administração & dosagem , Ratos , Espectrometria de Massas em Tandem
8.
PLoS One ; 12(3): e0174270, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28339488

RESUMO

Preharvest sprouting reduces the maize quality and causes a significant yield loss in maize production. vp-wl2 is a Mutator (Mu)-induced viviparous mutant in maize, causing white or pale yellow kernels, dramatically reduced carotenoid and ABA content, and a high level of zeta-carotene accumulation. Here, we reported the cloning of the vp-wl2 gene using a modified digestion-ligation-amplification method (DLA). The results showed that an insertion of Mu9 in the first intron of the zeta-carotene desaturase (ZDS) gene results in the vp-wl2 mutation. Previous studies have suggested that ZDS is likely the structural gene of the viviparous9 (vp9) locus. Therefore, we performed an allelic test using vp-wl2 and three vp9 mutants. The results showed that vp-wl2 is a novel allele of the vp9 locus. In addition, the sequences of ZDS gene were identified in these three vp9 alleles. The vp-wl2 mutant gene was subsequently introgressed into four maize inbred lines, and a viviparous phenotype was observed with yield losses from 7.69% to 13.33%.


Assuntos
Genes de Plantas , Mutação , Oxirredutases/genética , Proteínas de Plantas/genética , Zea mays/fisiologia , Alelos , Zea mays/genética
9.
Mol Plant ; 10(3): 470-482, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-27825944

RESUMO

Regulation of gene expression at the post-transcriptional level is of crucial importance in the development of an organism. Here we present the characterization of a maize gene, U6 biogenesis-like 1 (UBL1), which plays an important role in kernel and seedling development by influencing pre-mRNA splicing. The ubl1 mutant, exhibiting small kernel and weak seedling, was isolated from a Mutator-tagged population. Transgenic complementation and three independent mutant alleles confirmed that UBL1, which encodes a putative RNA exonuclease belonging to the 2H phosphodiesterase superfamily, is responsible for the phenotype of ubl1. We demonstrated that UBL1 possess the RNA exonuclease activity in vitro and found that loss of UBL1 function in ubl1 causes decreased level and abnormal 3' end constitution of snRNA U6, resulting in splicing defect of mRNAs. Through the in vitro and in vivo studies replacing two histidines with alanines in the H-X-T/S-X (X is a hydrophobic residue) motifs we demonstrated that these two motifs are essential for the normal function of UBL1. We further showed that the function of UBL1 may be conserved across a wide phylogenetic distance as the heterologous expression of maize UBL1 could complement the Arabidopsis ubl1 mutant.


Assuntos
RNA Nuclear Pequeno/genética , Plântula/genética , Zea mays/genética , Íntrons/genética , Processamento de RNA/genética
10.
Biochim Biophys Acta ; 1860(2): 384-91, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26116914

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality and poor prognosis. Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways have been implicated in promoting tumor cell proliferation and invasion of HCC cells. METHODS: As a potential inhibitor of tumor metastasis, the role of Raf kinase inhibitor protein (RKIP) in HCC development and the functional relevance with MAPK and NF-κB signaling pathways were investigated. The levels of RKIP expression were examined in human HCC tissues and correlated with tumor stages and metastatic status. Function of RKIP in cellular proliferation, migration, invasion and apoptosis was investigated in HCC cell lines by either overexpressing or knocking down RKIP expression. Mouse xenograft model was established to assess the effect of RKIP expression on tumor growth. RESULTS: Our results demonstrated decreased RKIP expression in HCC tissues and a strong correlation with tumor grade and distant metastasis. Manipulation of RKIP expression in HCCLM3 and HepG2 cells indicated that RKIP functioned to inhibit HCC cell motility and invasiveness, and contributed to tumor growth inhibition in vivo. Mechanistic studies showed that the function of RKIP was mediated through MAPK and NF-κB signaling pathways. However, cell type-dependent RKIP regulation on these two pathways was also suggested, indicating the complex nature of signaling network. CONCLUSION: Our study provides a better understanding on the molecular mechanisms of HCC metastasis and sets the foundation for the development of targeted therapeutics for HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteína de Ligação a Fosfatidiletanolamina/fisiologia , Transdução de Sinais/fisiologia , Animais , Carcinoma Hepatocelular/secundário , Movimento Celular , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/fisiologia , Invasividade Neoplásica
12.
Zhonghua Zhong Liu Za Zhi ; 33(5): 358-62, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21875465

RESUMO

OBJECTIVE: To investigate the expression of RKIP, p65 and pERK in hepatocellular carcinoma (HCC) and theIr correlation with invasion and metastasis of HCC. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RKIP mRNA. The expression levels of RKIP, p65 and pERK proteins in HCC tumor and peritumoral tissues were determined by immunohistochemistry and Western blot analysis. Statistical analysis was performed to determine the relationship between their expression and clinicopathological parameters. RESULTS: RKIP protein expression level (RKIP/actin) was 0.579 ± 0.380 in HCCs, 1.178 ± 0.659 in peritumoral tissues and 1.115 ± 0.442 in normal liver tissues. The pERK protein level was 1.023 ± 0.478, 0.605 ± 0.367 and 0.461 ± 0.293, p65 protein level was 0.83 ± 0.376, 0.63 ± 0.337 and 0.466 ± 0.345, respectively. Immunohistochemistry analysis showed that the RKIP positive rates in HCCs, peritumoral tissues and normal liver tissues, were 22.2%, 86.0%, and 93.8%, positive rates of p65 were 73.6%, 56.0% and 37.5%, positive rates of pERK were 65.3%, 38.0% and 31.3%, respectively. Statistical analysis revealed that there was a significant difference in RKIP protein expression levels (P < 0.05), but no significant difference in RKIP mRNA expression levels (P > 0.05) among HCC tumors, peritumoral tissues and normal liver tissues. The p65-positive and pERK-positive rates were higher in tumor tissues than that in peritumoral tissues and in normal liver tissues (P < 0.05), but RKIP-positive rates were lower in tumor tissues than that in paritumoral tissues and normal liver tissues (P < 0.05). RKIP protein expression levels were significantly lower in HCCs with intrahepatic or lymphatic metastasis than that in without. The RKIP positive rates in moderately and well differentiated HCCs were significantly higher than that in poorly differentiated HCCs. There was a relationship between RKIP and pERK expressions (P = 0.04), but RKIP expression was not correlated with p65 expression in HCCs (P = 0.143). CONCLUSIONS: Our findings indicate that the down-regulation of RKIP expression may serve as a predictive marker for HCC development, progression and metastasis, which may contribute to the elevated ERK activity. The inhibiting effect of RKIP on invasion and metastasis of liver cancer cells may be due to the down-regulation of pERK expression rather than p65 expression.


Assuntos
Carcinoma Hepatocelular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Hepáticas , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteína de Ligação a Fosfatidiletanolamina/genética , Fosforilação , RNA Mensageiro/metabolismo , Fator de Transcrição RelA/metabolismo
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