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1.
Cell Mol Life Sci ; 80(6): 160, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210406

RESUMO

We previously reported that permanent ischemia induces marked dysfunction of the autophagy-lysosomal pathway (ALP) in rats, which is possibly mediated by the transcription factor EB (TFEB). However, it is still unclear whether signal transducer and activator of transcription 3 (STAT3) is responsible for the TFEB-mediated dysfunction of ALP in ischemic stroke. In the present study, we used AAV-mediated genetic knockdown and pharmacological blockade of p-STAT3 to investigate the role of p-STAT3 in regulating TFEB-mediated ALP dysfunction in rats subjected to permanent middle cerebral occlusion (pMCAO). The results showed that the level of p-STAT3 (Tyr705) in the rat cortex increased at 24 h after pMCAO and subsequently led to lysosomal membrane permeabilization (LMP) and ALP dysfunction. These effects can be alleviated by inhibitors of p-STAT3 (Tyr705) or by STAT3 knockdown. Additionally, STAT3 knockdown significantly increased the nuclear translocation of TFEB and the transcription of TFEB-targeted genes. Notably, TFEB knockdown markedly reversed STAT3 knockdown-mediated improvement in ALP function after pMCAO. This is the first study to show that the contribution of p-STAT3 (Tyr705) to ALP dysfunction may be partly associated with its inhibitory effect on TFEB transcriptional activity, which further leads to ischemic injury in rats.


Assuntos
Autofagia , Fator de Transcrição STAT3 , Animais , Ratos , Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Isquemia/metabolismo , Lisossomos/metabolismo , Fosforilação , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
2.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34782465

RESUMO

Ischemic stroke can induce neurogenesis. However, most stroke-generated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone-releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 µg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation-reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice.


Assuntos
Hormônio Liberador de Hormônio do Crescimento/agonistas , Hormônio Liberador de Hormônio do Crescimento/metabolismo , AVC Isquêmico/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hormônio Liberador de Hormônio do Crescimento/genética , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/metabolismo , Plasticidade Neuronal , Fármacos Neuroprotetores , Proteínas Tirosina Quinases/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos
3.
Anal Chem ; 95(9): 4529-4535, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36814089

RESUMO

Sensitive detection of miRNA targets in complex biological samples possesses great value in biopsy analysis and disease diagnosis but is still challenging because of low abundance and nonspecific interferences. In this work, self-primer DNA polymerization-propelled stochastic walkers (SWs) were proposed to detect miRNA-24 by combining magnetic microbeads (MMBs) and flow cytometry. The MMBs not only provide a three-dimensional interface for DNA walkers but also facilitate the enrichment and isolation of RNA targets from complex biological samples such as serum. The SWs can be initiated to walk through the entire surface of MMBs and transduce RNA walking into amplified fluorescence signals, with the detection limit of miRNA-24 at 0.95 pM. Moreover, this strategy integrating with flow cytometry was demonstrated to have good specificity with other homologous miRNAs. This platform offers promising applications in RNA biosensing and biomedical diagnostics.


Assuntos
Técnicas Biossensoriais , MicroRNAs , MicroRNAs/análise , Microesferas , Polimerização , Limite de Detecção , DNA/análise , Fenômenos Magnéticos
4.
Small ; 19(12): e2205903, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36638250

RESUMO

DNA cascaded circuits have great potential in detecting low abundance molecules in complex biological environment due to their powerful signal amplification capability and nonenzymatic feature. However, the problem of the cascaded circuits is that the design is relatively complex and the kinetics is slow. Herein, a new design paradigm called catalyst-accelerated circular cascaded circuits is proposed, where the catalyst inlet is implanted and the reaction speed can be adjusted by the catalyst concentration. This new design is very simple and only requires three hairpin probes. Meanwhile, the results of a series of studies demonstrate that the reaction speed can be accelerated and the sensitivity can be also improved. Moreover, endogenous mRNA can also be used as a catalyst to drive the circuits to amplify the detection of target miRNA in live cells and in mice. These catalyst-accelerated circular cascaded circuits can substantially expand the toolbox for intracellular low abundance molecular detection.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Animais , Camundongos , DNA Circular , DNA , MicroRNAs/genética , RNA Mensageiro , Cinética , Técnicas Biossensoriais/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos
5.
Phys Chem Chem Phys ; 25(38): 26270-26277, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37743842

RESUMO

We study the regulation of the electronic and spin transport properties of the WGe2N4 monolayer by adsorbing 4d transition metal atoms (Y-Cd) using density functional theory combined with non-equilibrium Green's function. It is found that the adsorption of transition metal atoms (except Pd, Ag and Cd atoms) can introduce a magnetic moment into the WGe2N4 monolayer. Among the transition metal atoms, the adsorption of Nb and Rh atoms transforms WGe2N4 from a semiconductor to a half-metal and a highly spin-polarized semiconductor, respectively. The half-metallic Nb-adsorbed WGe2N4 system is selected to investigate the spin transport properties, and a high magnetoresistance ratio of 107% is achieved. In both parallel and antiparallel magnetization configurations, the spin filtering efficiency reaches close to 100% in the whole bias range, and the antiparallel magnetization configuration exhibits a dual spin filtering effect with a rectification ratio of up to 104. Our study predicts that the adsorption of 4d transition metal heteroatoms is an effective method to regulate the electronic and magnetic properties of WGe2N4 towards high-performance spintronic devices.

6.
Phys Chem Chem Phys ; 24(3): 1849-1859, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34988568

RESUMO

The spin-resolved transport properties of molecular logic devices composed of two Mn porphyrin molecules connected to each other via a six-carbon atomic chain were studied using the non-equilibrium Green's function combined with density functional theory. The molecules were symmetrically connected to armchair graphene nanoribbon electrodes through four-carbon atomic chains on the left- and right-hand sides. Our calculations revealed that the spin-resolved current-voltage curves depend on the initial spin setting of the transition metal Mn atoms and carbon atoms on the zigzag edges where the electrodes come in contact with the molecule. By simultaneously regulating the spin orientations of the intermediate functional molecules and the zigzag edges of the armchair graphene nanoribbon electrodes, seven spin polarization configurations were obtained. These configurations were examined in this study considering the spin-related symmetry of molecular junctions. By meticulously selecting different combinations according to the specific input and output signals, YES, NOT, OR, NOR, and XOR multifarious spin logic devices were created. The findings of this study are expected to contribute toward the extension of molecular junction functions in future spintronic integrated circuit design and further miniaturization.

7.
Phys Chem Chem Phys ; 24(47): 29057-29063, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36437710

RESUMO

Diodes have been widely studied as one of the most commonly used electronic components in circuits, and it is important to find diodes with an excellent rectification performance. Herein, we investigate the electronic and transport properties of Schottky contact diodes based on zigzag hydrogenated blue phosphorene nanoribbons, by employing density functional theory combined with the non-equilibrium Green's function. It is found that the adsorption of transition metal atoms Sc/Cr/Ti and Ni on the top site of blue phosphorene nanoribbons leads to metallic and semiconducting properties, respectively. Devices consisting of the planar contact of the metallic and semiconducting nanoribbons show rectifying behavior due to the Schottky barriers of the homojunctions. The current is preferential to flow from the semiconducting side to the metallic side. The rectification ratio of the Sc-Ni device and the Cr-Ni device can reach up to 108, which is much higher than that of traditional p-n junctions of about 105-107. The high rectification ratio at low bias regions, together with the low threshold voltages and negligible reverse currents, make blue phosphorene nanoribbon homojunctions ideal rectifier diodes.

8.
Stroke ; 52(5): 1809-1821, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33874744

RESUMO

Background and Purpose: CAPN1 (calpain1)­an intracellular Ca2+-regulated cysteine protease­can be activated under cerebral ischemia. However, the mechanisms by which CAPN1 activation promotes cerebral ischemic injury are not defined. Methods: In the present study, we used adeno-associated virus-mediated genetic knockdown and pharmacological blockade (MDL-28170) of CAPN1 to investigate the role of CAPN1 in the regulation of the autophagy-lysosomal pathway and neuronal damage in 2 models, rat permanent middle cerebral occlusion in vivo model and oxygen-glucose­deprived primary neuron in vitro model. Results: CAPN1 was activated in the cortex of permanent middle cerebral occlusion­operated rats and oxygen-glucose deprivation­exposed neurons. Genetic and pharmacological inhibition of CAPN1 significantly attenuated ischemia-induced lysosomal membrane permeabilization and subsequent accumulation of autophagic substrates in vivo and in vitro. Moreover, inhibition of CAPN1 increased autophagosome formation by decreasing the cleavage of the autophagy regulators BECN1 (Beclin1) and ATG (autophagy-related gene) 5. Importantly, the neuron-protective effect of MDL-28170 on ischemic insult was reversed by cotreatment with either class III-PI3K (phosphatidylinositol 3-kinase) inhibitor 3-methyladenine or lysosomal inhibitor chloroquine (chloroquine), suggesting that CAPN1 activation-mediated impairment of autophagic flux is crucial for cerebral ischemia-induced neuronal damage. Conclusions: The present study demonstrates for the first time that ischemia-induced CAPN1 activation impairs lysosomal function and suppresses autophagosome formation, which contribute to the accumulation of substrates and aggravate the ischemia-induced neuronal cell damage. Our work highlights the vital role of CAPN1 in the regulation of cerebral ischemia­mediated autophagy-lysosomal pathway defects and neuronal damage.


Assuntos
Autofagia/fisiologia , Isquemia Encefálica/metabolismo , Calpaína/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Neurônios/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Dipeptídeos/farmacologia , Modelos Animais de Doenças , Masculino , Neurônios/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
9.
Mol Hum Reprod ; 27(8)2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34240166

RESUMO

Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Dendritic cells (DCs) are thought to confer fetal-maternal immunotolerance and play a crucial role in ensuring a successful pregnancy. A decrease of plasmacytoid dendritic cells (pDCs) was found to be involved in RSA, but the underlying mechanisms of decreased pDC in RSA remain unclear. MicroRNAs (miRNAs) play critical roles in RSA as well as the development, differentiation and functional regulation of pDCs; however, the regulatory effect of miRNAs on pDC in RSA has not been fully investigated. Here we demonstrated that both the proportion of pDC and signal transducer and activator of transcription (STAT3)/transcription factor 4 (Tcf4/E2-2) expression decreased in the peripheral blood mononuclear cells and decidua of patients with RSA compared to those with normal pregnancy (NP), and there was a significantly positive correlation between pDC and STAT3 mRNA. MiRNA microarray assay and quantitative reverse transcription PCR results showed that miR-6875-5p expression was markedly increased in women with RSA and negatively correlated with mRNA expression level of STAT3. Up-regulated miR-6875-5p could sensitively discriminate patients with RSA from NP subjects. Overexpression of miR-6875-5p significantly down-regulated the mRNA expression of STAT3 and E2-2 as well as the protein and phosphorylation level of STAT3, while miR-6875-5p knockdown showed opposite results. Dual luciferase reporter verified that miR-6875-5p regulated STAT3 expression by directly binding to its 3'untranslated region. Overall, our results suggested that increased miR-6875-5p is involved in RSA by decreasing the differentiation of pDCs via inhibition of the STAT3/E2-2 signaling pathway. miR-6875-5p may be explored as a promising diagnostic marker and therapeutic target for RSA.


Assuntos
Aborto Habitual/imunologia , Células Dendríticas/citologia , MicroRNAs/metabolismo , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/fisiologia , Proteína 2 Semelhante ao Fator 7 de Transcrição/fisiologia , Regiões 3' não Traduzidas/genética , Aborto Habitual/genética , Adulto , Diferenciação Celular , Decídua/metabolismo , Células Dendríticas/metabolismo , Feminino , Genes Reporter , Células HEK293 , Humanos , Leucócitos Mononucleares/metabolismo , Gravidez
10.
Phys Chem Chem Phys ; 23(20): 11852-11862, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33988194

RESUMO

The development of highly sensitive, low-power consuming, stable and recyclable gas sensing devices at room temperature has become an important solution for environmental safety detection. Utilizing a two-dimensional metalloporphyrin monolayer for gas sensing is appealing due to its large specific surface area and high surface activity. A two-dimensional manganese porphyrin monolayer (2DMnPr) is selected from 2D metalloporphyrins with 3d metal centers due to its semi-metallicity to explore its gas sensing properties. Using first-principles calculations, we systematically investigate the electronic structures and adsorption characteristics of gas molecules with toxicity and greenhouse effect on the surface of 2DMnPr, including H2S, CO, CO2, SO2, NO and NO2. The strength of the interaction and charge transfer between the 2DMnPr surface and the adsorbed molecules have a direct effect on the electronic properties and the sensing properties of the adsorbent surface. The sensing performance of the 2DMnPr adsorbent is evaluated via two observable parameters: work function and electrical conductivity. The work functions of 2DMnPr after the adsorption of CO, SO2, NO and NO2 gas molecules increase by different degrees depending on the charge transfer, and those of the H2S and CO2 cases decrease. In our simulation, adsorption of CO, SO2, NO and NO2 gas molecules affects the electronic properties of 2DMnPr markedly, and current-voltage characteristics within a low bias range uncover the superior sensitivity of the conductivity of the 2DMnPr monolayer to these molecules. Besides, the sensing performance is demonstrated to be stable under strain and at room temperature. The desorption time of a gas is positively related to its adsorption energy. The recovery time of CO is predicted to be short enough to realize sustainable detection at room temperature, and the SO2, NO and NO2 gases can also be desorbed at higher temperatures. These results demonstrate that 2DMnPr enables the sensitive detection of these gases and predict the potential application of 2DMnPr as an ultra-sensitive, low-power, stable and recyclable gas sensor at room temperature.

11.
Mediators Inflamm ; 2021: 8876484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981184

RESUMO

Thrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombospondin-2 (TSP-2) has been associated with activation of "anti-inflammatory" T-regulatory cells (Tregs). In this study, we investigated the effects of both TSP-1 and TSP-2 overexpression on macrophage polarization and activation in vitro and in vivo. We analyzed the effects of TSP-1 and TSP-2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP-2 overexpression effectively attenuated LPS-induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro. Furthermore, TSP-2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP-2 can modulate inflammation and could therefore be a potential therapeutic target against LPS-induced ARDS.


Assuntos
Síndrome do Desconforto Respiratório/prevenção & controle , Trombospondina 1/fisiologia , Trombospondinas/fisiologia , Animais , Permeabilidade Capilar , Polaridade Celular , Células Cultivadas , Citocinas/biossíntese , Terapia Genética , Lipopolissacarídeos , Pulmão/patologia , Lesão Pulmonar/prevenção & controle , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/fisiologia , Síndrome do Desconforto Respiratório/induzido quimicamente
12.
Nanotechnology ; 31(22): 225705, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995789

RESUMO

Monolayer (ML) graphdiyne, a two-dimensional semiconductor with appropriate band gap and high carrier mobility, is a promising candidate for channel material in field effect transistors (FETs). Using density functional theory combined with non-equilibrium Green's function method, we systematically investigate the contact and transport properties of graphdiyne FETs with various electrodes, including metals (Cu, Au, Ni, Al and Ag) and MXenes (Cr2C, Ta2C and V2C). Strong interaction can be found between ML graphdiyne and the Cu, Ni and MXenes electrodes with indistinguishable band structure of ML graphdiyne, while weak or medium interaction exists in the contacts of ML graphdiyne and the Au, Al and Ag electrodes where the band structure of ML graphdiyne remains intact. Despite the different contact interactions, Ohmic contacts are generated with all considered electrode materials owing to the weak Fermi level pinning of graphdiyne. The linear I-V characteristic curve verifies the Ohmic contact between Au electrode and graphdiyne ultimately. The theoretically calculated Schottky barrier heights of graphdiyne with Cu electrode are consistent with the available experimental data. Our calculation suggests that graphdiyne is an excellent channel material of FETs forming desired Ohmic contacts with wide-ranging electrodes and thus is promising to fabricate high performance FETs.

13.
Phys Chem Chem Phys ; 22(28): 16063-16071, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32633289

RESUMO

The recent production of phosphorene nanoribbons provides a platform for designing phosphorene-based high-speed electronic devices. Introducing a magnetic moment to phosphorene nanoribbons for spintronics application is attractive. Based on density functional theory combined with the non-equilibrium Green's function method, the electronic, magnetic and spin-polarized transport properties of phosphorene nanoribbons modified by adsorption and substitutional doping of 4d transition metal atoms (Y, Zr, Nb and Mo) are investigated systematically. The results show that both the adsorption and the doping of 4d transition metal atoms can introduce a magnetic moment into phosphorene nanoribbons, except the Y- and Nb-doping cases. The adsorption shows superior performance in terms of modulating the electronic and magnetic properties of phosphorene nanoribbons compared to substitutional doping, exhibiting higher spin polarization near the Fermi level with a narrower band gap. This discrepancy originates from the different electronic redistribution in the adsorption and doping situations. Furthermore, the nanoribbons with adsorbed 4d transition metal atoms exhibit excellent spin-polarized transport properties: a giant magnetoresistance ratio of the Mo-adsorbed nanoribbon reaches over 108 under low bias; the Y-Mo-adsorbed nanoribbons with parallel spin configurations show a spin filtering effect of about 100% with the bias larger than 0.1 V, and those with antiparallel spin configurations exhibit a dual spin filtering effect in an applied bias range of (-0.2 V, 0.2 V). Our results demonstrate that 4d-transition-metal-atom adsorption is a favourable approach to modify the electronic, magnetic and transport properties of phosphorene nanoribbons, thus providing a reference for the rational design of spintronic devices based on phosphorene nanoribbons.

14.
Phys Chem Chem Phys ; 22(48): 28074-28085, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33289744

RESUMO

Monolayer C2N is promising for next-generation electronic and optoelectronic applications due to its appropriate band gap and high carrier efficiency. However, relative studies have been held back due to the lack of high-quality electrode contacts. Here, we comprehensively study the electronic and transport properties of monolayer C2N with a series of electrode materials (Al, Ti, Ni, Cu, Ag, Pt, V2C, Cr2C and graphene) by using the nonequilibrium Green's function (NEGF) method combined with density functional theory (DFT). The monolayer C2N forms Ohmic contacts with the Ti/Cu/Ag electrode material in both armchair and zigzag directions, whereas Ohmic contact is only formed in the zigzag direction of the C2N-Al field effect transistor. However, the C2N-Ni, -Pt, -V2C, -Mo2C, -graphene contact systems form n-type Schottky contacts in either the armchair or zigzag direction owing to the relatively strong Fermi level pinning (the pinning factor S = 0.32 in the armchair direction and S = 0.26 in the zigzag direction). By insertion of BN or graphene between the C2N and Pt electrode in the armchair direction of contact systems, the Fermi level pinning can be effectively weakened due to the suppression of metal-induced gap states. Conspicuously, an Ohmic contact is realized in the C2N field effect transistors with the BN-Pt electrode, suggesting a possible approach to fabricating high-performance devices. Our study is conducive to selecting appropriate electrode materials for C2N-based field effect transistors.

15.
Phys Chem Chem Phys ; 21(22): 11755-11763, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31114815

RESUMO

Modulation of the electronic and magnetic structure of blue phosphorene nanoribbons to explore the potential application in spintronics is appealing. Using density functional theory in combination with the non-equilibrium Green's function method, the energetic, electronic, magnetic, and spin-resolved transport properties of hydrogenated armchair and zigzag blue phosphorene nanoribbons with surface modification by 3d transition metal atoms (ranging from Sc to Ni) were systematically investigated. The blue phosphorene nanoribbons were found to be highly capable of adsorbing impurity atoms, and the adatoms prefer a 2D growth mode on the nanoribbons. The band structures of the blue phosphorene nanoribbons were effectively modulated by the adatoms: the bandgap dramatically decreased with remarkable spin-polarization, except in the case of Ni. The spin-resolved transport properties of Sc-adsorbed zigzag blue phosphorene nanoribbons were selectively investigated to explore the potential application in spintronics, and a giant magnetoresistance effect of above 500 was found. This work suggests that the surface adsorption of 3d transition metal heteroatoms is a feasible and effective approach to functionalize blue phosphorene nanoribbons for spintronic applications.

16.
Phys Chem Chem Phys ; 21(9): 4879-4887, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30778495

RESUMO

Modulating the electronic and magnetic properties of phosphorene is important for fabricating multi-functional electronic and spintronic devices. Employing density functional theory combined with the non-equilibrium Green's function, we systematically investigate the electronic, magnetic and transport properties of hydrogenated armchair phosphorene nanoribbons chemically modified by 3d transition metal atoms (Sc, Ti, V, Cr, Mn, Fe, Co and Ni). With chemical adsorption of transition metal atoms, the phosphorene nanoribbons exhibit excellent spin-polarized transport properties. A giant magnetoresistance effect is found with Ti, Fe and Mn adsorption, in which ratios higher than 102 for the Ti and Mn cases, and 105 for the Fe case, are exhibited. Moreover, in the bias range of (-0.2 V, 0.2 V), the Ti, V, Mn and Fe-adsorbed nanoribbons with parallel spin configurations demonstrate a remarkable bias-independent spin filtering efficiency at about 100%, while the Fe and Mn-adsorbed nanoribbons with antiparallel spin configuration show a dual spin filtering effect. The spin-polarized electronic transport properties are closely related to the band structures. Remarkable spin-polarization of the current occurs when the dispersed and flat bands near the Fermi level originate from different spin orientations. The magnetic moments of transition metal adatoms on nanoribbons are reduced by 0.2-2 µB relative to the isolated atoms due to electron rearrangement and charge transfer, which results in various degrees of spin polarization. These results provide a fundamental understanding of the electronic, magnetic and transport properties of transition metal modified hydrogenated armchair phosphorene nanoribbons, and suggest a referential approach to manufacture spintronic devices based on phosphorene.

17.
ESC Heart Fail ; 11(3): 1305-1316, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38243645

RESUMO

Recent findings indicate that fluctuations in blood glucose could potentially increase the risk of unfavourable outcomes in individuals with cardiovascular conditions. The objective of the research was to assess the correlation between glycaemic variability (GV) and the mortality of patients with heart failure (HF) through a comprehensive review and meta-analysis. Longitudinal follow-up studies comparing the mortality risk between HF patients with higher and lower GV were identified by searching Medline, Embase, Web of Science, and Cochrane Library databases. The results were combined using a random-effects model that accounted for the potential variability. The meta-analysis included nine cohort studies involving 76 843 patients diagnosed with HF, out of which 35 853 patients died within a follow-up period of up to 86 months. The combined findings indicated that a significant increase in GV was linked to an elevated risk of mortality in patients with HF during the follow-up period (RR 2.18, 95% CI 1.61 to 2.96, P < 0.001, I2 = 83%). The relationship between GV and mortality in HF patients was not significantly influenced by the patients' diabetic status (diabetic or non-diabetic), type of GV (acute or long-term GV), study design (prospective or retrospective), country of the study (Asian or non-Asian), follow-up durations, or the scores of study quality (P-values for subgroup differences all >0.05). A high GV could be a risk factor of mortality of patients with HF.


Assuntos
Glicemia , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Glicemia/metabolismo , Glicemia/análise , Saúde Global , Taxa de Sobrevida/tendências , Prognóstico , Fatores de Risco
18.
Front Pharmacol ; 15: 1290128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384299

RESUMO

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvß3 and α5ß1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model. Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE. Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvß3, and α5ß1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16. Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.

19.
Nanoscale ; 15(20): 9106-9115, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37133349

RESUMO

Multifunctional nanoscale devices integrating multiple functions are of great importance for meeting the requirements of next-generation electronics. Herein, using first-principles calculations, we propose multifunctional devices based on the two-dimensional monolayer MoSi2As4, where a single-gate field-effect transistor (FET) and FET-type gas sensor are integrated. After introducing the optimizing strategies, such as underlap structures and dielectrics with a high dielectric constant (κ), we designed a 5 nm gate-length MoSi2As4 FET, whose performance fulfilled the key criteria of the International Technology Roadmap for Semiconductors (ITRS) for high-performance semiconductors. Under the joint adjustment of the underlap structure and high-κ dielectric material, the on/off ratio of the 5 nm gate-length FET reached up to 1.38 × 104. In addition, driven by the high-performance FET, the MoSi2As4-based FET-type gas sensor showed a sensitivity of 38% for NH3 and 46% for NO2. Moreover, the weak interaction between NH3 (NO2) and MoSi2As4 favored the recycling of the sensor. Furthermore, the sensitivity of the sensor could be effectively improved by the gate voltage, and was increased up to 67% (74%) for NH3 (NO2). Our work provides theoretical guidance for the fabrication of multifunctional devices combining a high-performance FET and sensitive gas sensor.

20.
Drug Deliv ; 30(1): 2241664, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37545034

RESUMO

Gradual loss of neuronal structure and function due to impaired blood-brain barrier (BBB) and neuroinflammation are important factors in multiple sclerosis (MS) progression. Our previous studies demonstrated that the C16 peptide and angiopoietin 1 (Ang-1) compound (C + A) could modulate inflammation and vascular protection in many models of MS. In this study, nanotechnology and a novel nanovector of the leukocyte chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) were used to examine the effects of C + A on MS. The acute experimental autoimmune encephalomyelitis (EAE) model of MS was established in Lewis rats. The C + A compounds were conjugated to control nano-carriers and fMLP-nano-carriers and administered to animals by intravenous injection. The neuropathological changes in the brain cortex and spinal cord were examined using multiple approaches. The stimulation of vascular injection sites was examined using rabbits. The results showed that all C + A compounds (C + A alone, nano-carrier C + A, and fMLP-nano-carrier C + A) reduced neuronal inflammation, axonal demyelination, gliosis, neuronal apoptosis, vascular leakage, and BBB impairment induced by EAE. In addition, the C + A compounds had minimal side effects on liver and kidney functions. Furthermore, the fMLP-nano-carrier C + A compound had better effects compared to C + A alone and the nano-carrier C + A. This study indicated that the fMLP-nano-carrier C + A could attenuate inflammation-related pathological changes in EAE and may be a potential therapeutic strategy for the treatment of MS and EAE.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Ratos , Animais , Coelhos , N-Formilmetionina Leucil-Fenilalanina/química , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Esclerose Múltipla/tratamento farmacológico , Lipossomos , Angiopoietina-1/uso terapêutico , Ratos Endogâmicos Lew , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Inflamação/tratamento farmacológico
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