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Sodium-ion layered oxides are one of the most highly regarded sodium-ion cathode materials and are expected to be used in electric vehicles and large-scale grid-level energy storage systems. However, highly air-sensitive issues limit sodium-ion layered oxide cathode materials to maximize cost advantages. Industrial and scientific researchers have been developing cost-effective air sensitivity treatment strategies with little success because the impurity formation mechanism is still unclear. Using density functional theory calculations and ab initio molecular dynamics simulations, this work shows that the poor air stability of O3-type NaMn1/3Fe1/3Ni1/3O2 (NMFNO) may be as follows: (1) low percentage of nonreactive (003) surface; (2) strong surface adsorption capacity and high surface reactivity; and (3) instability of the surface sodium ions. Our physical images point out that the high reactivity of the NMFNO surface originates from the increase in electron loss and unpaired electrons (magnetic moments) of the surface oxygen active site as well as the enhanced metal coactivation effect due to the large radius of the sodium ion. We also found that the hydrolysis reaction requires a higher reactivity of the surface oxygen active site, while the carbon hybridization mode transformation in carbonate formation depends mainly on metal activation and does not even require the involvement of surface oxygen active sites. Based on the calculation results and our proposed physical images, we discuss the feasibility of these treatment strategies (including surface morphology modulation, cation/anion substitution, and surface configuration design) for air-sensitive issues.
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As an important half-reaction for electrochemical water splitting, electrocatalytic hydrogen evolution reaction suffers from sluggish kinetics, and it is still urgent to search high efficiency non-platinum-based electrocatalysts. Mo-based catalysts such as Mo2 C, MoO2 , MoP, MoS2 , and MoNx have emerged as promising alternatives to Pt/C owing to their similar electronic structure with Pt and abundant reserve of Mo. On the other hand, due to the adjustable topology, porosity, and nanostructure of metal organic frameworks (MOFs), MOFs are extensively used as precursors to prepare nano-electrocatalysts. In this review, for the first time, the progress of Mo-MOFs-derived electrocatalysts for hydrogen evolution reaction is summarized. The preparation method, structures, and catalytic performance of the catalysts are illustrated based on the types of the derived electrocatalysts including Mo2 C, MoO2 , MoP, MoS2 , and MoNx . Especially, the commonly used strategies to improve catalytic performance such as heteroatoms doping, constructing heterogeneous structure, and composited with noble metal are discussed. Moreover, the opportunities and challenges in this area are proposed to guide the designment and development of Mo-based MOF derived electrocatalysts.
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This study examines the anti-inflammatory activity of cynaropicrin against lipopolysaccharide (LPS) in vitro and ovalbumin (OVA)-challenged asthma in mice. Cynaropicrin's antimicrobial effects were tested on Escherichia coli (E. coli) and Streptococcus pyogenes (S. pyogenes) using the disc diffusion technique. Cytotoxicity was assessed with an (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The anti-inflammatory property was evaluated in LPS-induced RAW264.7 cells, while OVA-challenged asthmatic mice were treated with 10 mg/kg of cynaropicrin. Key inflammatory and antioxidant markers were quantified, and lung histology was examined to confirm therapeutic roles. The antimicrobial studies proved that cynaropicrin effectively inhibited the growth of E. coli and S. pyogenes. Cynaropicrin displayed no cytotoxicity on RAW264.7 cells. Furthermore, it significantly inhibited inflammatory cytokine synthesis upon LPS induction. Cynaropicrin treatment decreased the inflammatory cell counts and also suppressed specific allergic markers in OVA-challenged mice. It also decreased nitric oxide and myeloperoxidase levels and reduced pulmonary edema. Cynaropicrin increased antioxidant levels and decreased proinflammatory cytokines in the asthmatic mice. Lung histological examination confirms the ameliorative potency of cynaropicrin against OVA-induced asthmatic pulmonary inflammation in mice. Our findings suggest cynaropicrin possesses significant ameliorative potency against allergen-induced pulmonary inflammation.
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Asma , Citocinas , Lipopolissacarídeos , Ovalbumina , Animais , Camundongos , Asma/tratamento farmacológico , Asma/induzido quimicamente , Asma/metabolismo , Asma/patologia , Lipopolissacarídeos/toxicidade , Células RAW 264.7 , Citocinas/metabolismo , Sesquiterpenos/farmacologia , Camundongos Endogâmicos BALB C , Escherichia coli , Streptococcus pyogenes , Anti-Inflamatórios/farmacologia , Masculino , Feminino , LactonasRESUMO
Hepatocellular carcinoma (HCC) is a globally prevalent malignancy, marked by genetic heterogeneity and intricate tumor microenvironment interactions. In this study, we undertook a detailed single-cell analysis of six active HCC patients, highlighting strong correlations between gene expression levels and cellular characteristics. UMAP clustering revealed seven distinct cell categories with associated gene expressions. A divergence was observed in tumor cells into high and low cuproptosis groups, each associated with distinct pathways: oxidative stress for the high cuproptosis group and inflammatory and angiogenesis pathways for the low group. CellChat analysis on the TCGA-LIHC cohort displayed unique intercellular interactions among hepatocytes, T cells, and other cells, with pathways like COLLAGEN and VEGF being pivotal. Functional enrichment analyses exposed pathways enriched between cuproptosis groups, with KEGG emphasizing diseases like Parkinson's. COX survival analysis identified key prognostic genes, revealing distinct survival rates between risk groups in TCGA and GSE14520 cohorts. Mutation data highlighted missense mutations, with TTN, TP53, and CTNNB1 being the most mutated in HCC. Immune infiltration analysis via CIBERSORTx indicated differences between risk groups in NK cells, neutrophils, and other cells. Our drug sensitivity investigation showed significant correlations between model genes and drug responsiveness, emphasizing the importance of patient risk stratification for therapeutic approaches. Further, ATP6V1G1 was recognized in its role in apoptosis and migration in HCC cells. In conclusion, our findings illuminate the complexities of HCC progression, potential predictive genetic markers for drug response, and the pivotal role of ATP6V1G1, suggesting avenues for targeted therapeutic strategies in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Genômica , Hepatócitos , Apoptose , Microambiente TumoralRESUMO
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in immunocompromised children with systemic lupus erythematosus (SLE). Prophylaxis against PJP in high-risk children is crucial, but the risk factors for PJP in children with SLE are not adequately characterized. This study sought to identify the risk factors for PJP in long-term glucocorticoid-treated pediatric SLE patients. METHODS: This study encompassed 71 treatment episodes involving 64 children with prolonged (≥4 weeks) high-dose (≥20 mg/d prednisone) steroid regimens. Fourteen treatment episodes involved the PJP, whereas others did not. Risk factors for PJP were assessed through Cox regression. The predictive value of these factors was evaluated using receiver operating characteristic curves. The incidence of PJP in different risk groups was compared using the Kaplan-Meier method. RESULTS: The creatinine (hazard ratio, 1.009; 95% confidence interval [CI], 1.001-1.017; p = 0.021) and the lowest lymphocyte count (hazard ratio, 0.007; 95% CI, 0.000-0.373; p = 0.014) were independent risk factors for PJP in children with SLE. The receiver operating characteristic curve showed that using creatinine greater than 72.5 µmol/L and the lowest lymphocyte count less than 0.6 × 109/L as risk predictors for PJP resulted in an area under the curve value of 0.934 (95% CI, 0.870-0.997; p < 0.001). The study revealed a significant increase in PJP prevalence (p < 0.001) in children with elevated creatinine levels and low lymphocyte count. CONCLUSIONS: Elevated levels of creatinine and decreased lymphocyte count are identified as distinct risk factors for PJP in children with SLE who receive prolonged high-dose steroid therapy.
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The efficiency of energy coupled to plasma during femtosecond (fs) laser filamentation plays a decisive role in a variety of filament applications such as remote fabrication and spectroscopy. However, the energy deposition characterization in the fs laser filament formed by a telescope, which provides an efficient way to extend the filament distance, has not yet been revealed. In the present study, we show that when the distance between the two lenses in a telescope changes, i.e., the effective focal length changes, there exists an optimal plateau energy deposition region in which the energy deposited into the filament per unit length called the average lineic energy deposition (ALED) remains at high levels, exhibiting a remarkable difference from the monotonic change in a single-lens focusing system. As a proof of principle, we examined the influence of the energy deposition on the ignition of a lean methane/air mixture, and found that the use of the telescope can efficiently extend the ignition distance when compared with a single-lens focusing system under the same incident laser energy condition. Our results may help understand the energy deposition behaviors in a variety of telescopic filaments and provide more options to manipulating laser ignition at a desired distance.
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Air lasing induced by laser filamentation opens a new route for research on atmospheric molecular physics and remote sensing. The generation of air lasing is composed of two processes, i.e., building up optical gain of air molecules in femtosecond time scale and emitting coherent radiation in picosecond time scale. Here, we focus on the emission mechanisms of N2 + air lasing and reveal, by examining the intensities and temporal profiles of N2 + lasing at 391â nm generated respectively in a time-varying polarization-modulated and a linearly polarized pump laser field under different nitrogen gas pressures, that the N2 + lasing can emit through either triggered super-radiance or seed amplification. We find that the two pressure-sensitive factors, i.e., the dipole dephasing time T2 and the population inversion density n, determine which of these two mechanisms dominates the N2 + lasing emission process, enabling manipulation of the transition from triggered super-radiance to seed amplification or vice versa. Our findings clarify the emission mechanism of N2 + lasing under different pressures and provide a deeper understanding of N2 + air lasing not only in the establishment of optical gain but also in the lasing emission process.
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The functionalization of noble metals is an effective approach to lowering the sensing temperature and improving the sensitivity of metal oxide semiconductor (MOS)-based gas sensors. However, there is a dearth of comparative analyses regarding the differences in sensitization mechanisms between the two functionalization modes of noble metal loading and doping. In this investigation, we synthesized Pt-doped CuO gas-sensing materials using a one-pot hydrothermal method. And for Pt-loaded CuO, Pt was deposited on the synthesized pristine CuO surface by using a dipping method. We found that both functionalization methods can considerably enhance the response and selectivity of CuO toward NO2 at low temperatures. However, we observed that CuO with Pt loading had superior sensing performance at 25 °C, while CuO with Pt doping showed more substantial response changes with an increase in the operating temperature. This is mainly due to the different dominant roles of electron sensitization and chemical sensitization resulting from the different forms of Pt present in different functionalization modes. For Pt doping, electron sensitization is stronger, and for Pt loading, chemical sensitization is stronger. The results of this study present innovative ideas for understanding the optimization of noble metal functionalization for the gas-sensing performance of metal oxide semiconductors.
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Femtosecond filament-induced breakdown spectroscopy (FIBS) is an efficient approach in remote and in situ detection of a variety of trace elements, but it was recently discovered that the FIBS of water is strongly dependent on the large-bandgap semiconductor property of water, making the FIBS signals sensitive to laser ionization mechanisms. Here, we show that the sensitivity of the FIBS technique in monitoring metal elements in water can be efficiently improved by using chirped femtosecond laser pulses, but an asymmetric enhancement of the FIBS intensity is observed for the negatively and positively chirped pulses. We attribute the asymmetric enhancement to their different ionization rates of water, in which the energy of the photons participating in the ionization process in the front part of the negatively chirped pulse is higher than that in the positively chirped pulse. By optimizing the pulse chirp, we show that the limit of detection of the FIBS technique for metal elements in water, e.g., aluminum, can reach to the sub-ppm level, which is about one order of magnitude better than that by the transform-limited pulse. We further examine the FIBS spectra of several representative water samples including commercial mineral water, tap water, and lake water taken from two different environmental zones, i.e., a national park and a downtown business district (Changchun, China), from which remarkably different concentrations of Ca, Na, and K elements of these samples are obtained. Our results provide a possibility of using FIBS for direct and fast metal elemental analysis of water in different field environments.
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Oligoelementos , Água , Lasers , Análise Espectral , SemicondutoresRESUMO
Optical transport networks (OTNs) are widely used in backbone- and metro-area transmission networks to increase network transmission capacity. In the OTN, it is particularly crucial to rationally allocate routes and maximize network capacities. By employing deep reinforcement learning (DRL)- and software-defined networking (SDN)-based solutions, the capacity of optical networks can be effectively increased. However, because most DRL-based routing optimization methods have low sample usage and difficulty in coping with sudden network connectivity changes, converging in software-defined OTN scenarios is challenging. Additionally, the generalization ability of these methods is weak. This paper proposes an ensembles- and message-passing neural-network-based Deep Q-Network (EMDQN) method for optical network routing optimization to address this problem. To effectively explore the environment and improve agent performance, the multiple EMDQN agents select actions based on the highest upper-confidence bounds. Furthermore, the EMDQN agent captures the network's spatial feature information using a message passing neural network (MPNN)-based DRL policy network, which enables the DRL agent to have generalization capability. The experimental results show that the EMDQN algorithm proposed in this paper performs better in terms of convergence. EMDQN effectively improves the throughput rate and link utilization of optical networks and has better generalization capabilities.
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Redes Neurais de Computação , Software , Algoritmos , AprendizagemRESUMO
Software-defined networking (SDN) has become one of the critical technologies for data center networks, as it can improve network performance from a global perspective using artificial intelligence algorithms. Due to the strong decision-making and generalization ability, deep reinforcement learning (DRL) has been used in SDN intelligent routing and scheduling mechanisms. However, traditional deep reinforcement learning algorithms present the problems of slow convergence rate and instability, resulting in poor network quality of service (QoS) for an extended period before convergence. Aiming at the above problems, we propose an automatic QoS architecture based on multistep DRL (AQMDRL) to optimize the QoS performance of SDN. AQMDRL uses a multistep approach to solve the overestimation and underestimation problems of the deep deterministic policy gradient (DDPG) algorithm. The multistep approach uses the maximum value of the n-step action currently estimated by the neural network instead of the one-step Q-value function, as it reduces the possibility of positive error generated by the Q-value function and can effectively improve convergence stability. In addition, we adapt a prioritized experience sampling based on SumTree binary trees to improve the convergence rate of the multistep DDPG algorithm. Our experiments show that the AQMDRL we proposed significantly improves the convergence performance and effectively reduces the network transmission delay of SDN over existing DRL algorithms.
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Fast detection of low-concentration exosomes in body fluids is of great significance in understanding the pathogenesis and disease diagnosis but is quite a challenging work due to the complex matrix, tedious pretreatment, and relatively poor sensitivity without the aid of instruments. In this work, by simply using a filter membrane to enrich the exosomes at low concentrations and the use of CuS nanoparticles as labels, we were able to detect exosomes at concentrations as low as 2 × 103 particles/µL in a complex matrix by the naked eye. Due to its high sensitivity, specificity, and simplicity, it can be used for the diagnosis of direct prostate cancer via a 5 mL urine sample within 2 h without the use of any instrument. This method can also be applicable for the detection of other biological nanoparticles, such as viruses, at low concentrations in a complex matrix, offering a promising candidate for point-of-care disease diagnosis with low cost.
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Líquidos Corporais , Exossomos , Nanopartículas , Humanos , Masculino , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
Fabricating electrical double-layer capacitors (EDLCs) with high energy density for various applications has been of great interest in recent years. However, activated carbon (AC) electrodes are restricted to a lower operating voltage because they suffer from instability above a threshold potential window. Thus, they are limited in their energy storage. The deposition of inorganic compounds' atomic layer deposition (ALD) aiming to enhance cycling performance of supercapacitors and battery electrodes can be applied to the AC electrode materials. Here, we report on the investigation of zinc oxide (ZnO) coating strategy in terms of different pulse times of precursors, ALD cycles, and deposition temperatures to ensure high electrical conductivity and capacitance retention without blocking the micropores of the AC electrode. Crystalline ZnO phase with its optimal forming condition is obtained preferably using a longer precursor pulse time. Supercapacitors comprising AC electrodes coated with 20 cycles of ALD ZnO at 70 °C and operated in TEABF4/acetonitrile organic electrolyte show a specific capacitance of 23.13 F g-1 at 5 mA cm-2 and enhanced capacitance retention at 3.2 V, which well exceeds the normal working voltage of a commercial EDLC product (2.7 V). This work delivers an additional feasible approach of using ZnO ALD modification of AC materials, enhancing and promoting stable EDLC cells under high working voltages.
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In many optoelectronic applications, patterning is required for functional and/or aesthetic purposes. However, established photolithographic technique cannot be applied directly to the hybrid perovskites, which are considered as promising candidates for optoelectronic applications. In this work, a wettability-assisted photolithography (WAP) process, which employs photolithography and one-step solution process to deposit hybrid perovskite, was developed for fabricating patterned hybrid perovskite films. Uniform pinhole-free hybrid perovskite films with sharp-edged micropatterns of any shapes can be constructed through the WAP process. Semitransparent solar cells with an adjustable active layer average visible transmittance of a wide range from 20.0% to 100% and regular solar cells based on patterned CH3NH3PbI3 perovskite films were fabricated to demonstrate that the WAP process was compatible with the manufacturing process of optoelectronic devices. With the widely equipped photolithographic facilities in the modern semiconductor industry, we believe the WAP process have a great potential in the industrial production of functionally or aesthetically patterned hybrid perovskite devices.
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BACKGROUND: Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. METHODS: The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. RESULTS: It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1ß, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological functions after TBI. We further demonstrated that ω-3 PUFA supplementation inhibited HMGB1 nuclear translocation and secretion and decreased expression of HMGB1 in neurons and microglia in the lesioned areas. Moreover, ω-3 PUFA supplementation inhibited microglial activation and the subsequent inflammatory response by regulating HMGB1 and the TLR4/NF-κB signaling pathway. CONCLUSIONS: The results of this study suggest that microglial activation and the subsequent neuroinflammatory response as well as the related HMGB1/TLR4/NF-κB signaling pathway play essential roles in secondary injury after TBI. Furthermore, ω-3 PUFA supplementation inhibited TBI-induced microglial activation and the subsequent inflammatory response by regulating HMGB1 nuclear translocation and secretion and also HMGB1-mediated activation of the TLR4/NF-κB signaling pathway, leading to neuroprotective effects.
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Lesões Encefálicas Traumáticas/patologia , Encefalite/dietoterapia , Ácidos Graxos Ômega-3/administração & dosagem , Proteína HMGB1/metabolismo , Microglia/efeitos dos fármacos , Neuroprostanos/administração & dosagem , Animais , Edema Encefálico/etiologia , Lesões Encefálicas Traumáticas/complicações , Proteínas de Ligação ao Cálcio/metabolismo , Córtex Cerebral/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/etiologia , Encefalite/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/patologia , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Fatores de TempoRESUMO
To compare the toxicity of landfill leachate exposure at the early stages of seed soaking and germination on maize, a field experiment was conducted to evaluate the physiological aspects of growth, yield and potential clastogenicity of root-tip cells. The maizes were treated with leachate at levels of 2%, 10%, 20%, 30% or 50% (V/V). First, the change of physiological indexes, including chlorophyll (Chl), Malondialdehyde (MDA) and Reactive oxygen species (ROS) levels, combined with yield all showed that soaking with leachate, but not germination, generated a greater ecological risk on maize. After a soaking treatment of maize with 50% leachate, the Chl, MDA and ROS levels during a vigorous growth period were 47.3%, 149.8% and 309.7%, respectively, of the control, whereas the yield decreased to 68.6% of the control. In addition, our results demonstrated that the leachate at lower levels could promote growth. This is mainly embodied in that the yield of maize treated with 10% leachate at the soaking stage increased to 116.0% of the control. Moreover, the cytological analysis experiment also demonstrated that the ecological risk of leachate still exists in both cases. Furthermore, the gray relational analysis showed that the ear row number and tassel branch number were the major factors affecting the yield of maize treated with 50% leachate at the stages of soaking and germination, respectively. In general, these results are helpful in understanding the phytotoxicity of leachate, which provides additional reference data for risk assessment and management of leachate.
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Monitoramento Ambiental , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água/toxicidade , Zea mays/efeitos dos fármacos , Clorofila , Germinação , Malondialdeído , Plântula/crescimento & desenvolvimento , Sementes , Testes de Toxicidade , Zea mays/crescimento & desenvolvimentoRESUMO
We propose a single layer all-dielectric metasurface lens to simultaneously convert and focus an incident linear polarization into a radial beam with high efficiency and high numerical aperture (NA). It shows a better focusing property compared with the linearly polarized metasurface lens for high NA. A tight spot size (0.502λ) is achieved for the NA = 0.94. Additionally, the emergent polarization can in principle be switched flexibly between radially and azimuthally polarized beams by the adjustment of incident polarization direction. It is expected that our scheme may have potential value in microscopy, material processing, medicine, particles accelerating and trapping, and so on.
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With great interest, we read the article "Relationships between PTEN gene mutations and prognosis in glioma: a meta-analysis" (by Xiao et al. Tumor Biol 35(7):6687-6693, 2014), which has reached important conclusions that the phosphatase and tensin homolog (PTEN) gene mutations were closely related to poor prognosis of glioma patients. Through quantitative analysis, the investigators (Xiao WZ et al.) showed that glioma patients with PTEN gene mutations exhibited a significantly shorter overall survival (OS) than those without PTEN gene mutations (HR = 3.66, 95 % CI = 2.02â¼5.30, P < 0.001). Ethnicity-stratified subgroup analysis demonstrated that PTEN gene mutations were closely linked to poor prognosis in glioma among Americans (HR = 3.72, 95 % CI = 1.72â¼5.73, P < 0.001), while similar correlations were not observed among populations in Sweden, Italy, and Malaysia (all P > 0.05). The meta-analysis results are encouraging. Nevertheless, some deficiencies still existed that we would like to raise.
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Neoplasias Encefálicas/genética , Glioma/genética , PTEN Fosfo-Hidrolase/genética , HumanosRESUMO
Dihydroartemisinin (DHA) is a semi-synthetic derivative of artemisinin, a well-tolerated and effective drug for malaria treatment, and has recently been shown to have antitumorigenic activity. However, the mechanistic basis of these activities in gliomas is unknown. The objective of this study was to evaluate whether DHA inhibits cell proliferation and invasion in glioma cells, and to elucidate the underlying mechanisms. The results demonstrate that DHA treatment significantly inhibited cell proliferation, migration and invasion, as determined using viability, transwell migration, and matrix penetration assays, respectively. Western blot analysis revealed that protein expression levels of a disintegrin and metalloproteinase 17 (ADAM17), and phosphorylated epidermal growth factor receptor and AKT (p-EGFR and p-AKT, respectively), were suppressed by DHA. EGFR and AKT phosphorylation was enhanced by stimulation with the ADAM17 agonist chemokine phorbol myristate acetate. These data suggest that DHA inhibits glioma proliferation and invasion through suppression of ADAM17 and downregulation of EGFR-PI3 K-AKT signaling.
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Antineoplásicos/farmacologia , Artemisininas/farmacologia , Glioma/tratamento farmacológico , Proteínas ADAM/metabolismo , Proteína ADAM17 , Antineoplásicos/uso terapêutico , Artemisininas/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacosRESUMO
SCAI (suppressor of cancer cell invasion), has been recently characterized as a novel tumor suppressor that inhibits the invasive migration of several human tumor cells. However, the expression pattern, biological role and molecular mechanism of SCAI in human glioma remain unknown. In this study, we found that levels of SCAI protein and mRNA expression were significantly down-regulated in glioma tissues and cell lines. Overexpression of SCAI inhibited, but silencing of SCAI robustly promoted the invasive and cancer stem cell-like phenotypes of glioma cells. Furthermore, we demonstrated that SCAI downregualtion activated the Wnt/ß-catenin signaling, and blockade of the Wnt/ß-catenin pathway abrogated the effects of SCAI downregulation on glioma cell aggressiveness. Taken together, our results provide the first demonstration of SCAI downregulation in glioma, and its downregulation contributes to increased glioma cell invasion and self-renewal by activating the Wnt/ß-catenin pathway.