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1.
Small ; 20(23): e2306425, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38150634

RESUMEN

N doping is an essential strategy to prolong electron diffusion length and improve the photovoltaic performance of p-i-n structured perovskite solar devices, but current n-dopants generally suffer from air instability, poor compatibility with perovskites, and the compensation from perovskite intrinsic defects, thus limiting their doping effectiveness. To address these issues, in this work, a new perovskite n-doping strategy is developed by incorporating an air-stable n-dopant (1-ethyl-3-methylimidazolium-2-carboxylate, EMIC) that has no detrimental effects on perovskite crystallinity and morphology. EMIC is soluble in most polar solvents and can be readily introduced into perovskite precursor solutions. Upon thermal annealing of perovskite films, the decarboxylation of EMIC releases imidazolylidene, a reactive species that highly tends to donate electrons and thus efficiently prolongs the electron diffusion length from 0.57 µm to over 1.21 µm. As a result, the blade-coated perovskite solar cells and modules realize high power conversion efficiencies of 24.3% and 20.6% at 7.4 mm2 and 25.0 cm2 aperture areas, respectively.

2.
J Environ Manage ; 352: 120044, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38184867

RESUMEN

The increasing contamination of water systems by antibiotics and heavy metals has become a growing concern. The intimately coupled photocatalysis and biodegradation (ICPB) approach offers a promising strategy for the effective removal of mixed pollutants. Despite some prior research on ICPB applications, the mechanism by which ICPB eliminates mixed pollutants remains unclear. In our current study, the ICPB approach achieved approximately 1.53 times the degradation rate of ciprofloxacin (CIP) and roughly 1.82 times the reduction rate of Cr (VI) compared to photocatalysis. Remarkably, after 30 days, the ICPB achieved a 96.1% CIP removal rate, and a 97.8% reduction in Cr (VI). Our investigation utilized three-dimensional fluorescence analysis and photo-electrochemical characterization to unveil the synergistic effects of photocatalysis and biodegradation in removal of CIP and Cr (VI). Incorporation of B-Bi3O4Cl (B-BOC) photocatalyst facilitated electron-hole separation, leading to production of ·O2-, ·OH, and h+ species which interacted with CIP, while electrons reduced Cr (VI). Subsequently, the photocatalytic products were biodegraded by a protective biofilm. Furthermore, we observed that CIP, acting as an electron donor, promoted the reduction of Cr (VI). The microbial communities revealed that the number of bacteria favoring pollutant removal increased during ICPB operation, leading to a significant enhancement in performance.


Asunto(s)
Ciprofloxacina , Contaminantes Ambientales , Antibacterianos , Biodegradación Ambiental , Cromo/química , Catálisis
3.
J Hepatol ; 79(6): 1418-1434, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37604269

RESUMEN

BACKGROUND & AIMS: Integrin αv (ITGAV, CD51) is regarded as a key component in multiple stages of tumor progression. However, the clinical failure of cilengitide, a specific inhibitor targeting surface CD51, suggests the importance of yet-unknown mechanisms by which CD51 promotes tumor progression. METHODS: In this study, we used several hepatocellular carcinoma (HCC) cell lines and murine hepatoma cell lines. To investigate the role of CD51 on HCC progression, we used a 3D invasion assay and in vivo bioluminescence imaging. We used periostin-knockout transgenic mice to uncover the role of the tumor microenvironment on CD51 cleavage. Moreover, we used several clinically relevant HCC models, including patient-derived organoids and patient-derived xenografts, to evaluate the therapeutic efficacy of cilengitide in combination with the γ-secretase inhibitor LY3039478. RESULTS: We found that CD51 could undergo transmembrane cleavage by γ-secretase to produce a functional intracellular domain (CD51-ICD). The cleaved CD51-ICD facilitated HCC invasion and metastasis by promoting the transcription of oxidative phosphorylation-related genes. Furthermore, we identified cancer-associated fibroblast-derived periostin as the major driver of CD51 cleavage. Lastly, we showed that cilengitide-based therapy led to a dramatic therapeutic effect when supplemented with LY3039478 in both patient-derived organoid and xenograft models. CONCLUSIONS: In summary, we revealed previously unrecognized mechanisms by which CD51 is involved in HCC progression and uncovered the underlying cause of cilengitide treatment failure, as well as providing evidence supporting the translational prospects of combined CD51-targeted therapy in the clinic. IMPACT AND IMPLICATIONS: Integrin αv (CD51) is a widely recognized pro-tumoral molecule that plays a crucial role in various stages of tumor progression, making it a promising therapeutic target. However, despite early promising results, cilengitide, a specific antagonist of CD51, failed in a phase III clinical trial. This prompted further investigation into the underlying mechanisms of CD51's effects. This study reveals that the γ-secretase complex directly cleaves CD51 to produce an intracellular domain (CD51-ICD), which functions as a pro-tumoral transcriptional regulator and can bypass the inhibitory effects of cilengitide by entering the nucleus. Furthermore, the localization of CD51 in the nucleus is significantly associated with the prognosis of patients with HCC. These findings provide a theoretical basis for re-evaluating cilengitide in clinical settings and highlight the importance of identifying a more precise patient subpopulation for future clinical trials targeting CD51.


Asunto(s)
Carcinoma Hepatocelular , Integrina alfaV , Neoplasias Hepáticas Experimentales , Neoplasias Hepáticas , Animales , Humanos , Ratones , Secretasas de la Proteína Precursora del Amiloide , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Integrina alfaV/genética , Integrina alfaV/metabolismo , Neoplasias Hepáticas/genética , Microambiente Tumoral
4.
J Environ Manage ; 347: 119111, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37774664

RESUMEN

Ultrasonication allows sludge reduction to be performed in situ during wastewater treatment, and the reflux point of the lysed sludge affects this performance. This study investigated the effects of reflux point (anaerobic stage, carbon/nitrogen (C/N) lowest stage, and aerobic stage) on sludge lysis-cryptic growth in an anaerobic/aerobic reactor and variations in the sludge and microbial community. The best reflux point occurred at the lowest C/N ratio stage, and a 50.96% reduction in excess sludge was achieved. The reflux of the lysed sludge to the aerobic stage reduced nitrogen and phosphorus removal. The reflux of the lysed sludge decreased the average sludge size, reaching 29.2 µm when reflux to the aerobic stage. Scanning electron microscopy showed that the sludge surface was unaffected by the reflux point. The Fourier-transform infrared spectrometry and X-ray photoelectron spectroscopy results showed that the most prominent variation in the intensity of the sludge functional groups occurred when the reflux was at the lowest C/N stage. The amount of extracellular polymeric substances decreased the most during reflux to the anaerobic stage. The sludge microbial communities varied with the reflux point, and the dominant phyla during reflux to the anaerobic, lowest C/N, and aerobic stages were Bacteroidetes, Firmicutes, and Bacteroidetes, respectively. Furthermore, the reflux point did not alter the metabolic pathway of sludge microorganisms but increased the number of enzymes in metabolic pathways.


Asunto(s)
Microbiota , Aguas Residuales , Aguas del Alcantarillado/química , Anaerobiosis , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos , Nitrógeno , Carbono
5.
J Environ Manage ; 347: 119249, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37812897

RESUMEN

The integrated photocatalysis and fluidized bed biofilm reactor (FBBR) is an attractive wastewater treatment technique for managing wastewater containing antibiotics. However, the fast recombination of photoinduced charge and low microbial activity limit the degradation and mineralization efficiency for antibiotics. To address this, we attempt to introduce magnetic field (MF) to the integrated system with B-doped Bi3O4Cl as the photocatalysts to effectively improve removal and mineralization of ciprofloxacin (CIP). As a consequence, the degradation rate reaches 96% after 40 d in integrated system with MF. The biofilm inside the integrated system with MF carrier can mineralize the photocatalytic products, thereby increasing the total organic carbon (TOC) degradation rate by more than 32%. The electrochemical experiment indicates the Lorentz force generated by MF can accelerate charge separation, increasing the electron concentration. Simultaneously, the increased amounts of electrons lead to the generation of more ·OH and ·O2-. MF addition also results in increased biomass, increased biological respiratory activity, microbial community evolution and accelerated microbial metabolism, enabling more members to biodegrade photocatalytic intermediates. Therefore, applied MF is an efficient method to enhance CIP degradation and mineralization by the integrated system.


Asunto(s)
Reactores Biológicos , Aguas Residuales , Antibacterianos , Ciprofloxacina , Biopelículas
6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(5): 557-561, 2023 Sep 30.
Artículo en Zh | MEDLINE | ID: mdl-37753897

RESUMEN

With the highlighted advantages of 3D printing technology in the field of dental prosthodontics, there is increasing in the numbers of registration applications for additive manufacturing customized dentures. However, there is still a lack of unified analysis in the core elements of process control, the key points of registration and the safety production quality control. Based on the current research status of the industry, the study is intended to clarify confusion and difficulties, deeply analyse the mechanism of the product defects, sort the core elements of process control, then try to establish a systematic evaluation system from product performance research, key process verification, production quality control and the description of registration files, so that it can provide help for practitioners to clarify research direction, establishing quality management system, improving the efficiency of registration and ensuring product quality.

7.
Appl Opt ; 61(31): 9198-9202, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36607054

RESUMEN

A practical method for dynamic color holographic display by using a computer-generated hologram (CGH) with a high space-bandwidth product is proposed, and a dynamic color holographic display system is designed by a space-division method. First, three primary color CGHs of different frames from a color movie are fabricated on holographic recording material by a self-made CGH microfilming system. Secondly, the CGH is fixed on an X-Y moving stage, which is controlled by the system in order to bring the CGH to the appointed position. Thirdly, three primary color lasers are used to reconstruct the CGH. The switch of the lasers is controlled by the system synchronous with the X-Y moving stage. The color video with high quality can be obtained after filtering the three primary color reconstructed wavefronts. The experimental results demonstrate that the proposed dynamic color holographic display method is effective. It has practical application value in high-quality CGH display.

8.
Nucleic Acids Res ; 48(4): 1715-1729, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-31912146

RESUMEN

N6-methyladenosine (m6A) is a reversible and dynamic RNA modification in eukaryotes. However, how cells establish cell-specific m6A methylomes is still poorly understood. Here, we developed a computational framework to systematically identify cell-specific trans regulators of m6A through integrating gene expressions, binding targets and binding motifs of large number of RNA binding proteins (RBPs) with a co-methylation network constructed using large-scale m6A methylomes across diverse cell states. We applied the framework and successfully identified 32 high-confidence m6A regulators that modulated the variable m6A sites away from stop codons in a cell-specific manner. To validate them, we knocked down three regulators respectively and found two of them (TRA2A and CAPRIN1) selectively promoted the methylations of the m6A sites co-localized with their binding targets on RNAs through physical interactions with the m6A writers. Knockdown of TRA2A increased the stabilities of the RNAs with TRA2A bound near the m6A sites and decreased the viability of cells. The successful identification of m6A regulators demonstrates a powerful and widely applicable strategy to elucidate the cell-specific m6A regulators. Additionally, our discovery of pervasive trans-acting regulating of m6A provides novel insights into the mechanisms by which spatial and temporal dynamics of m6A methylomes are established.


Asunto(s)
Adenosina/análogos & derivados , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ARN/genética , ARN/genética , Adenosina/química , Adenosina/genética , Linaje de la Célula/genética , Supervivencia Celular/genética , Regulación de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen/métodos , Células Hep G2 , Humanos , Metilación , Procesamiento Postranscripcional del ARN/genética
9.
Nucleic Acids Res ; 48(13): 7182-7196, 2020 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-32510157

RESUMEN

Hippo-YAP signaling pathway functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. We found that knockout (KO) of Mst1 and Mst2, two key components of the Hippo signaling in mouse embryonic stem cells (ESCs), resulted in a disruption of differentiation into mesendoderm lineage. To further uncover the underlying regulatory mechanisms, we performed a series of ChIP-seq experiments with antibodies against YAP, ESC master transcription factors and some characterized histone modification markers as well as RNA-seq assays using wild type and Mst KO samples at ES and day 4 embryoid body stage respectively. We demonstrate that YAP is preferentially co-localized with super-enhancer (SE) markers such as Nanog, Sox2, Oct4 and H3K27ac in ESCs. The hyper-activation of nuclear YAP in Mst KO ESCs facilitates the binding of Nanog, Sox2 and Oct4 as well as H3K27ac modification at the loci where YAP binds. Moreover, Mst depletion results in novel SE formation and enhanced liquid-liquid phase-separated Med1 condensates on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Our study reveals a novel mechanism on how Hippo-YAP signaling pathway dictates ESC lineage differentiation.


Asunto(s)
Diferenciación Celular , Proteínas Serina-Treonina Quinasas/fisiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Madre Embrionarias de Ratones , Serina-Treonina Quinasa 3 , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAP
10.
J Environ Manage ; 301: 113859, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34597949

RESUMEN

In order to strengthen the treatment of low-concentration ammonia nitrogen wastewater at low temperature, iron-loaded activated carbon (Fe-AC) with ultrasonic impregnation method was used as the filter material of biofilter process. The performance and mechanism of ammonia nitrogen removal from simulated secondary wastewater by iron-loaded biological activated carbon filter (Fe-BACF) were studied at 10 °C. The characterization results showed that iron was loaded on the surface of AC in the form of Fe2O3, and the specific surface area, total pore volume, pore size and alkaline functional group content of Fe-AC were obviously increased. After the formation of biofilm on the surface of filter media, the average removal rate of ammonia nitrogen by Fe-BACF (97.9%) was significantly higher than that of conventional BACF (87.8%). The improved surface properties increased the number and metabolic activity of microorganisms, and promoted the secretion of EPS on the surface of Fe-BAC. The results of high-throughput sequencing showed that the existence of Fe optimized the bacterial community structure on the surface of Fe-BAC, with the increase of the abundances of psychrophilic bacteria and ammonia nitrogen removal bacteria. The mechanism of enhanced ammonia nitrogen removal by Fe-BACF was the joint action of many factors, among which the main causal relationship was that modification of iron could optimize the number and category of microorganisms on Fe-BAC surface by improving the surface properties, thus improving the biological nitrogen removal ability. Results of this study provided a practical way for the treatment of low ammonia nitrogen wastewater in cold regions.


Asunto(s)
Amoníaco , Aguas Residuales , Amoníaco/análisis , Reactores Biológicos , Carbón Orgánico , Desnitrificación , Filtración , Hierro , Nitrógeno/análisis , Temperatura
11.
J Environ Manage ; 316: 115213, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35561493

RESUMEN

To enhance the decolorization of methyl orange (MO), Fe-N complex biochar (Fe-N-BC) was developed as an accelerator in the sodium sulfide (Na2S) reduction system. The decolorization effect and mechanism of MO in the Fe-N-BC/Na2S composite system were studied. Surface pore analysis, Raman spectroscopy, FT-IR, XPS, and electrochemical analysis were used to characterize Fe-N-BC and unmodified biochar (BC). These results demonstrated that Fe-N-BC had better adsorption performance (specific surface area 463.46 m2 g-1) and electron transfer capacity than BC. By adding Fe-N-BC to the Na2S reduction system for MO, it was found that the decolorization of MO was greatly improved (increased by 93%). Besides, the effects of critical factors such as the initial concentration of Na2S, the dosage of Fe-N-BC, pH value, and temperature on the decolorization rate of MO were evaluated. Through the analysis of the action mechanism, the cooperation mode of Fe-N-BC and Na2S was to form an infinite cycle of adsorption-reduction-regeneration, so as to realize the rapid decolorization of MO. On the one hand, Fe-N-BC could adsorb MO and Na2S on its surface to increase the contact opportunity; on the other hand, it could act as a redox mediator to accelerate the electron transfer of the reduction reaction. In addition, the degradation of MO by Na2S was also an in-situ regeneration of Fe-N-BC. These findings may provide a feasible method to decolorize azo dyes quickly by cooperating with chemical reducing agents from a new perspective.


Asunto(s)
Contaminantes Químicos del Agua , Adsorción , Compuestos Azo , Carbón Orgánico , Hierro/química , Espectroscopía Infrarroja por Transformada de Fourier , Sulfuros , Contaminantes Químicos del Agua/química
12.
Opt Express ; 29(20): 32439-32452, 2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34615314

RESUMEN

We introduced a kind of novel perfect optical vortex beam, which we termed herein as perfect helical Mathieu vortex (PHMV) beams. The theoretical mechanism regarding the construction of PHMV beams was divided into two parts: generation of helical Mathieu (HM) beams using the stationary phase method and then Fourier transform of HM beams into the PHMV beams. Accordingly, the experimental system for generating PHMV beams was built as follows. Based on the complex amplitude modulation method, HM beams of different orders and ellipticity were generated using an amplitude-type spatial light modulator (SLM) and a radial-helical phase mask. Subsequently, an achromatic Fourier transform lens was illuminated using the HM beams, and the PHMV beams were presented on the focal plane after the Fourier transform lens. The experimental results were consistent with theoretical predictions. Compared with the classical perfect optical vortex (POV) beams, the PHMV beams still retained the property of ring radius independent of topological charge values. The distribution pattern of the PHMV beams can be controlled by the topological charges and elliptical parameters. Furthermore, two important optical properties of the PHMV beams were theoretically elucidated. First, we proved that the PHMV beams carry a fractional order orbital angular momentum (OAM). Second, we found that the complex amplitudes of any two PHMV beams with the same elliptical parameter but different order numbers are orthogonal to each other.

13.
Phys Chem Chem Phys ; 22(5): 2743-2747, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31984390

RESUMEN

Resistive switching (RS) memory behaviors are observed in an Ag|α-Fe2O3|Ti device after operating under an ultralow bias voltage of ±0.1 V. An SET voltage of ∼20 mV is obtained under illumination. Multilevel RS memory is realized under photoelectric signal control. The separation and fast transfer of hole-electron pairs are responsible for the enhanced RS memory under illumination.

14.
J Environ Sci (China) ; 96: 109-116, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32819685

RESUMEN

Refractory organic pollutants in water threaten human health and environmental safety, and advanced oxidation processes (AOPs) are effective for the degradation of these pollutants. Catalysts play vital role in AOPs, and Ce-based catalysts have exhibited excellent performance. Recently, the development and application of Ce-based catalysts in various AOPs have been reported. Our study conducts the first review in this rapid growing field. This paper clarifies the variety and properties of Ce-based catalysts. Their applications in different AOP systems (catalytic ozonation, photodegradation, Fenton-like reactions, sulfate radical-based AOPs, and catalytic sonochemistry) are discussed. Different Ce-based catalysts suit different reaction systems and produce different active radicals. Finally, future research directions of Ce-based catalysts in AOP systems are suggested.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Catálisis , Humanos , Oxidación-Reducción , Aguas Residuales
15.
Opt Express ; 27(13): 18085-18093, 2019 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-31252756

RESUMEN

We propose and experimentally demonstrate annular arrayed-Airy beams (AAABs) carrying vortex arrays by combining multiple beams. The propagation dynamics and abrupt autofocusing property are studied. The focal intensity can be greatly increased by two orders of magnitude by increasing vortex array number. Furthermore, the autofocusing property is also enhanced significantly. This tightly autofocusing property would be advantageous for the generation of high intensity laser, optical manipulation, medical treatments, and nonlinear effects.

16.
Opt Lett ; 44(12): 3158-3161, 2019 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-31199405

RESUMEN

We report a technique to break the depth of field (DOF) limit in optical coherence tomography (OCT) using a finite energy Airy beam. The Airy beam is generated using a phase mask in a Fourier transform schematic and provides the DOF improvement due to its low diffraction. We compare Airy beam OCT with conventional Gaussian beam OCT using lateral resolution and sensitivity. Experimental data from the polystyrene beads in water as well as lemon tissue confirm the extension of DOF up to 10 mm in Airy beam OCT, while the DOF of Gaussian beam OCT is less than 3.0 mm. We also demonstrate that a modified Airy beam can be effectively used in OCT by adjusting the truncating factor of the Airy beam via changing the pattern scale of the phase mask. This result provides a selection method for the use of a finite energy Airy beam in OCT.

17.
Water Sci Technol ; 77(1-2): 296-303, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29377815

RESUMEN

To better understand the microbial oil removal enhancement process by a magnetic field, the effect of a static magnetic field (SMF) on the microscopic characteristics of highly efficient biodegradation oil-removing bacteria was studied. The Acinetobacter sp. B11 strain with a 53.6% oil removal rate was selected as the reference bacteria. The changes in the microscopic characteristics of Acinetobacter sp. B11 such as the cell surface morphology, cell permeability and cell activity of the bacteria were investigated. The results showed that low-intensity magnetic fields (15-35 mT) improved the ability of Acinetobacter sp. B11 to remove oil by 11.9% at 25 mT compared with that of bacteria with no magnetic field. Without destroying the cell membrane, the low-intensity magnetic fields increased the cell membrane permeability and improved the activity of superoxide dismutase (SOD), which effectively enhanced the oil degradation performance of the bacteria.


Asunto(s)
Acinetobacter/crecimiento & desarrollo , Campos Magnéticos , Petróleo/análisis , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Acinetobacter/metabolismo , Biodegradación Ambiental , Permeabilidad de la Membrana Celular , Modelos Teóricos
18.
J Opt Soc Am A Opt Image Sci Vis ; 33(8): 1523-30, 2016 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-27505650

RESUMEN

We introduce another type of Pearcey beam, namely, dual Pearcey (DP) beams, based on the Pearcey function of catastrophe theory. DP beams are experimentally generated by applying Fresnel diffraction of bright elliptic rings. Form-invariant Bessel distribution beams can be regarded as a special case of DP beams. Subsequently, the basic propagation characteristics of DP beams are identified. DP beams are the result of the interference of two half DP beams instead of two classical Pearcey beams. Moreover, we also verified that half DP beams (including special-case parabolic-like beams) generated by half elliptical rings (circular rings) are a new member of the family of form-invariant beams.

19.
Appl Opt ; 55(27): 7694-9, 2016 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-27661599

RESUMEN

We construct and generate symmetric accelerating caustic beams (ACBs) by using 3/2-order phase-only masks with elliptical contour based on optical caustics and diffraction theory. The symmetric ACBs are a type of bimodal accelerating caustic beam with two quasi-constant intensity peaks, very similar to the combination of two face-to-face Airy-like beams judging by appearance. Their fundamental optical morphology and force properties of particles in ACBs are subsequently provided. The unique optical properties of ACBs can be exploited for practical uses, such as accelerating electrons and clearing micrometer-sized particles as a laser micrometer-sized "water pump" instead of a laser micrometer-sized "snowblower" of accelerating Airy beams.

20.
J Neuroinflammation ; 11: 41, 2014 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-24594021

RESUMEN

BACKGROUND: Depression has most often been diagnosed in patients with temporal lobe epilepsy (TLE), but the mechanism underlying this association remains unclear. In this study, we report that indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in epilepsy-associated depressive-like behavior. METHODS: Rats which develop chronic epilepsy following pilocarpine status epilepticus exhibited a set of interictal disorders consistent with depressive-like behavior. Changes of depressive behavior were examined by taste preference test and forced swim test; brain IL-1ß, IL-6 and IDO1 expression were quantified using real-time reverse transcriptase PCR; brain kynurenine/tryptophan and serotonin/tryptophan ratios were analyzed by liquid chromatography-mass spectrometry. Oral gavage of minocycline or subcutaneous injection of 1-methyltryptophan (1-MT) were used to inhibite IDO1 expression. RESULTS: We observed the induction of IL-1ß and IL-6 expression in rats with chronic TLE, which further induced the upregulation of IDO1 expression in the hippocampus. The upregulation of IDO1 subsequently increased the kynurenine/tryptophan ratio and decreased the serotonin/tryptophan ratio in the hippocampus, which contributed to epilepsy-associated depressive-like behavior. The blockade of IDO1 activation prevented the development of depressive-like behavior but failed to influence spontaneous seizures. This effect was achieved either indirectly, through the anti-inflammatory tetracycline derivative minocycline, or directly, through the IDO antagonist 1-MT, which normalizes kynurenine/tryptophan and serotonin/tryptophan ratios. CONCLUSION: Brain IDO1 activity plays a key role in epileptic rats with epilepsy-associated depressive-like behavior.


Asunto(s)
Depresión/etiología , Depresión/patología , Epilepsia del Lóbulo Temporal/complicaciones , Hipocampo/enzimología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Animales , Cromatografía Liquida , Citocinas/metabolismo , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Preferencias Alimentarias , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/patología , Cloruro de Litio/toxicidad , Masculino , Espectrometría de Masas , Minociclina/uso terapéutico , Ratas , Ratas Wistar , Estadísticas no Paramétricas , Factores de Tiempo , Triptófano/análogos & derivados , Triptófano/metabolismo , Triptófano/uso terapéutico
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