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A rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of doxorubicin (DOX) in mouse plasma and tissues, including the heart, liver, spleen, lung, kidney and tumor, and to investigate the pharmacokinetics and distribution in mice. In this study, daunorubicin (DNR) was used as an internal standard, and the mobile phase consisted of ammonium formate 2 mM containing 0.1 % formic acid (A) and acetonitrile (B), the chromatographic column was ACQUITY UPLC BEHTM C18 with a gradient elution at a flow rate of 0.2 mL/min. Electrospray ionization (ESI) in positive ion pattern was utilized for the ion separation of DOX, with the ions used for quantitative analysis being DOX m/z 544.28 â 397.10 and DNR m/z 528.35 â 321.08, respectively. The results showed that a good linear relationship in the calibration curve range of 1-800 ng/mL in mouse plasma and 1-2500 ng/g in tissues (R2 > 0.99) with the limits of quantification of 1 ng/mL in plasma and tissues. The method exhibited good matrix effect and extraction recovery, with the intra-day and inter-day precision of plasma and tissue were less than 10.3 % and 15.4 %, and the relative error (RE) were both less than ±14.8 % and ±18.9 %, respectively. The stability results under different conditions were found to be accurate. It also revealed the distribution of DOX in various tissues of mice, with the concentration ranking as liver > heart > kidney > spleen > lung > tumor. This method was successfully used to the study for the pharmacokinetics in plasma and drug distribution in tissues of BALB/c mice.
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Understanding the dynamics of neural networks and their response to external stimuli is crucial for unraveling the mechanisms associated with learning processes. In this study, we hypothesized that electrical stimulation (ES) would lead to significant alterations in the activity patterns of hippocampal neuronal networks and investigated the effects of low-frequency ES on hippocampal neuronal populations using the microelectrode arrays (MEAs). Our findings revealed significant alterations in the activity of hippocampal neuronal networks following low-frequency ES trainings. Post-stimulation, the neural activity exhibited an organized burst firing pattern characterized by increased spike and burst firings, increased synchronization, and enhanced learning behaviors. Analysis of peri-stimulus time histograms (PSTHs) further revealed that low-frequency ES (1Hz) significantly enhanced neural plasticity, thereby facilitating the learning process of cultured neurons, whereas high-frequency ES (>10Hz) impeded this process. Moreover, we observed a substantial increase in correlations and connectivity within neuronal networks following ES trainings. These alterations in network properties indicated enhanced synaptic plasticity and emphasized the positive impact of low-frequency ES on hippocampal neural activities, contributing to the brain's capacity for learning and memory.
Subject(s)
Electric Stimulation , Hippocampus , Learning , Nerve Net , Neuronal Plasticity , Animals , Hippocampus/physiology , Nerve Net/physiology , Learning/physiology , Cells, Cultured , Neuronal Plasticity/physiology , Rats , Neurons/physiology , Action Potentials/physiology , Rats, Sprague-DawleyABSTRACT
Introduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs. Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated. Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice. Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.
Subject(s)
Hydroxyethyl Starch Derivatives , Hyperuricemia , Luteolin , Nanoparticles , Animals , Nanoparticles/chemistry , Hydroxyethyl Starch Derivatives/chemistry , Hydroxyethyl Starch Derivatives/pharmacokinetics , Hydroxyethyl Starch Derivatives/administration & dosage , Hydroxyethyl Starch Derivatives/pharmacology , Luteolin/pharmacokinetics , Luteolin/pharmacology , Luteolin/chemistry , Luteolin/administration & dosage , Mice , Caco-2 Cells , Hyperuricemia/drug therapy , Hyperuricemia/blood , Humans , Male , Particle Size , Disease Models, Animal , Solubility , Uric Acid/blood , Uric Acid/chemistry , Biological Availability , Administration, Oral , Drug StabilityABSTRACT
Intracavity optical metasurfaces with compact and flexible light manipulation capabilities, effectively enrich the implementation of miniaturized and user-friendly orbital angular momentum (OAM) laser sources. Here we demonstrate a wavelength-tunable figure-9 Yb-doped vortex fiber laser solely with standard non-polarization-maintaining single-mode fibers, which utilizes a gap-surface plasmon (GSP) metasurface as the intracavity mode regulation component to generate OAM beams, extending the avenues and related applications for cost-effective OAM laser sources. Gained by the broadband operation range of the metasurface, the figure-9 fiber laser could emit OAM light with center wavelength tunable from 1020â nm to 1060â nm and of high mode purity (about 90%). OAM beams with different topological charges such as l = ±1 have been obtained by changing the metasurface design. The proposed fiber laser with the intracavity GSP metasurface provides a reliable and customized output of OAM beams at the laser source, holding great promise for a wide range of applications in optical communications, sensing, and super-resolution imaging.
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Metasurfaces for edge detection through spatial analog calculations have attracted much attention due to advantages such as a flexible design and small footprint. Up until now, most studies have focused on single-wavelength operation in the near-infrared or visible regions, while little work has been done in the ultraviolet band. It is of significance to explore metasurfaces for edge detection in the ultraviolet band for their great potential in high-resolution imaging and lithography. Here, we propose a dual-wavelength H f O 2 metasurface for edge detection working at 273 nm and 293 nm, with 25% and 72% efficiency, respectively, controlled by the linear polarization of the incident light. The efficient dual-wavelength second-order differential calculation in the ultraviolet band of the metasurface has been confirmed by 1D signal and 2D image processing. It may find applications in the fields of computer vision and bioimaging.
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Resonant plasmonic metasurfaces have attracted much attention for great potential in augmenting nonlinear optical conversion at the nanoscale and thus related sensing and integrated optics applications. In this work, we use the nonlinear scattering theory to numerically investigate enhanced second-harmonic generation (SHG) from Fano metasurfaces which consist of gold asymmetric double-bars. We find that the Fano resonance at the fundamental wavelength boosts the nonlinear response by more than a factor of 60. On this basis, by introducing translational and rotational structural asymmetries, the SHG signal is further amplified because of the broken mirror symmetry. More specifically, under the optimal condition, the previously suppressed SHG component can be greatly released and play a more important role compared to the original existing SHG component in an extra 6-fold enhancement in total SHG intensity. The 360-fold enhancement by tailoring both resonance quality and structural asymmetries indicates the clear and important roles of both linear resonance and local-field distribution in reaching the largest SHG emission. Our results are a step towards enlarging SHG responses of more complex plasmonic nanostructures.
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Recently, deep reinforcement learning (DRL) for metasurface design has received increased attention for its excellent decision-making ability in complex problems. However, time-consuming numerical simulation has hindered the adoption of DRL-based design method. Here we apply the Deep learning-based virtual Environment Proximal Policy Optimization (DE-PPO) method to design the 3D chiral plasmonic metasurfaces for flexible targets and model the metasurface design process as a Markov decision process to help the training. A well trained DRL agent designs chiral metasurfaces that exhibit the optimal absolute circular dichroism value (typically, â¼ 0.4) at various target wavelengths such as 930 nm, 1000 nm, 1035 nm, and 1100 nm with great time efficiency. Besides, the training process of the PPO agent is exceptionally fast with the help of the deep neural network (DNN) auxiliary virtual environment. Also, this method changes all variable parameters of nanostructures simultaneously, reducing the size of the action vector and thus the output size of the DNN. Our proposed approach could find applications in efficient and intelligent design of nanophotonic devices.
Subject(s)
Algorithms , Neural Networks, Computer , Computer Simulation , PolicyABSTRACT
Due to the small core diameter, a single-core multimode fiber (MMF) has been extensively investigated for endoscopic imaging. However, an extra light path is always utilized for illumination in MMF imaging system, which takes more space and is inapplicable in practical endoscopy imaging. In order to make the imaging system more practical and compact, we proposed a dual-function MMF imaging system, which can simultaneously transmit the illumination light and the images through the same imaging fiber. Meanwhile, a new deep learning-based encoder-decoder network with full-connected (FC) layers was designed for image reconstruction. We conducted an experiment of transmitting images via a 1.6 m long MMF to verify the effectiveness of the dual-function MMF imaging system. The experimental results show that the proposed network achieves the best reconstruction performance compared with the other four networks on different datasets. Besides, it is worth mentioning that the cropped speckle patterns can still be used to reconstruct the original images, which helps to reduce the computing complexity significantly. We also demonstrated the ability of cross-domain generalization of the proposed network. The proposed system shows the potential for more compact endoscopic imaging without external illumination.
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A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10-8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10-7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.
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This study focuses on media framings of COVID-19 in Chinese social and cultural contexts. After analysing nine weeks' news reports of Xinwen Lianbo, one of China's mainstream media, we discovered that the metaphorical war frame dominated throughout the corpus but it did not remain the same. Some of its semantic concepts like the type of war evolved over time. There are also several minor metaphors such as race, challenge, chess and combination blow metaphors, which are not as dominant as the war metaphor but should by no means be neglected. The race and challenge metaphors are complementary with the war metaphor to frame COVID-19, while the chess and combination blow metaphors are culturally loaded. What's more, literal frames like responsibility and collaboration were also found in the corpus. All frames, whether metaphorical or literal, work together to shape what COVID-19 was, what roles people should play and what people could do. In this study, we intend to explore how media framings of COVID-19 were related to media and government's responses as well as how they might have contributed to the public's responses. The media is an important source of information, whose role in public health emergencies deserves our attention.
Subject(s)
COVID-19 , Communication , Mass Media , Metaphor , COVID-19/epidemiology , COVID-19/psychology , China , Humans , Language , SARS-CoV-2 , Social BehaviorABSTRACT
BACKGROUND: Pancreatic cancer is a fatal disease with a very poor prognosis due to its characteristic insidious symptoms, early metastasis, and chemoresistance. Circular RNAs (circRNAs) are involved in the development of pancreatic cancer. AIM: Hence, the aim of this study is to elucidate the mechanism of circRNA_000864 in regulating BTG2 expression in pancreatic cancer by binding to miR-361-3p. METHODS: CircRNA_000864, miR-361-3p, and BTG2 expression patterns in the pancreatic cancer tissues were detected by RT-qPCR. Correlation among circRNA_000864, miR-361-3p, and BTG2 was evaluated by RNA-pull down assay, RNA Immunoprecipitation assay, and dual-luciferase reporter gene assay. After ectopic expression and depletion experiments, 5-ethynyl-2'-deoxyuridine assay, Transwell assay, and flow cytometry were employed to assess the cell proliferation, migration and invasion, cell cycle, and apoptosis. Xenotransplantation of nude mice was conducted to detect the effects of circRNA_000864, miR-361-3p, and BTG2 on tumor growth. RESULTS: CircRNA_000864 and BTG2 were poorly expressed, and miR-361-3p was highly expressed in the pancreatic cancer tissues. CircRNA_000864 bound to miR-361-3p could target BTG2. Cell proliferation, migration, and invasion were inhibited, and the cell cycle arrest and apoptosis were stimulated after overexpression of circRNA_000864 or BTG2 or downregulation of miR-361-3p. Overexpression of circRNA_000864 or downregulation of miR-361-3p also decreased the tumor growth in vivo. CONCLUSIONS: Conjointly, our findings elicited that the overexpression of circRNA_000864 could promote BTG2 expression to inhibit pancreatic cancer development by binding to miR-361-3p, which represents an appealing therapeutic target for the treatment of pancreatic cancer.
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This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.
Subject(s)
Anti-Allergic Agents/therapeutic use , Cytokines/metabolism , Dermatitis, Atopic/drug therapy , Drugs, Chinese Herbal/therapeutic use , Inflammation/prevention & control , Animals , Anti-Allergic Agents/pharmacology , Cell Line , Dendritic Cells/pathology , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Epithelial Cells/metabolism , Fluorescein-5-isothiocyanate/toxicity , Inflammation/metabolism , Inflammation/pathology , Keratinocytes/drug effects , Keratinocytes/metabolism , Lymphocytes/metabolism , Lymphocytes/pathology , Mice, Inbred BALB C , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic useABSTRACT
We demonstrate second-harmonic generation with ultranarrow resonances in hybrid plasmon-fiber cavities, formed by depositing single-crystalline gold nanorods onto the surface of tapered microfibers with diameters in the range of 1.7-1.8 µm. The localized surface plasmon mode of the single gold nanorod efficiently couples with a whispering gallery mode of the fiber, resulting in a very narrow hybrid plasmon-fiber resonance with a high quality factor Q of up to 250. When illuminated with a tunable 100 fs laser, a sharp SHG peak narrower than half of the spectral width of the impinging laser emerges, superimposed on a broad multiphoton photoluminescence background. The enhancement of the SHG peak of the hybrid system is typically 1000-fold when compared to that of a single gold nanorod alone. Tuning the laser over the hybrid resonance enables second-harmonic spectroscopy and yields an ultranarrow line width as small as 6.4 nm. We determine the second-harmonic signal to rise with the square of the laser power, while the multiphoton photoluminescence background rises with powers between 4 and 6, indicating a very efficient higher-order process. A coupled anharmonic oscillator model is able to describe the linear as well as second-harmonic resonances very well. Our work will open the door to the simultaneous utilization of narrow whispering gallery resonances together with high plasmonic near-field enhancement and should allow for nonlinear sensing and extremely efficient nonlinear light generation from ultrasmall volumes.
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To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An in vitro study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases.
Subject(s)
Cytokines/immunology , Hypersensitivity/prevention & control , Interleukin-33/immunology , Saponins/pharmacology , Th2 Cells/immunology , Triterpenes/pharmacology , Animals , Humans , Hypersensitivity/immunology , Hypersensitivity/pathology , Inflammation/immunology , Inflammation/pathology , Inflammation/prevention & control , Mice , Mice, Inbred BALB C , Th2 Cells/pathology , Thymic Stromal LymphopoietinABSTRACT
Titanium nitride (TiN) is a novel refractory plasmonic material which can sustain high temperatures and exhibits large optical nonlinearities, potentially opening the door for high-power nonlinear plasmonic applications. We fabricate TiN nanoantenna arrays with plasmonic resonances tunable in the range of about 950-1050 nm by changing the antenna length. We present second-harmonic (SH) spectroscopy of TiN nanoantenna arrays, which is analyzed using a nonlinear oscillator model with a wavelength-dependent second-order response from the material itself. Furthermore, characterization of the robustness upon strong laser illumination confirms that the TiN antennas are able to endure laser irradiation with high peak intensity up to 15 GW/cm(2) without changing their optical properties and their physical appearance. They outperform gold antennas by one order of magnitude regarding laser power sustainability. Thus, TiN nanoantennas could serve as promising candidates for high-power/high-temperature applications such as coherent nonlinear converters and local heat sources on the nanoscale.
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We perform second harmonic spectroscopy of aluminum nanoantenna arrays that exhibit plasmonic resonances at the second harmonic wavelength between 450 and 570 nm by focusing sub-30 fs laser pulses tunable from 900 to 1140 nm onto the nanoantenna arrays. We find that a plasmonic resonance at the second harmonic wavelength boosts the overall nonlinear process by more than an order of magnitude. In particular, in the measurement the resonant second harmonic polarization component is a factor of about 70 stronger when compared to the perpendicular off-resonant second harmonic polarization. Furthermore, the maximum of the second harmonic conversion efficiency is found to be slightly blue-shifted with respect to the peak of the linear optical far-field spectrum. This fact can be understood from a simple model that accounts for the almost off-resonant absorption at the fundamental wavelength and the resonant emission process at the second harmonic.
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We introduce a spectroscopic method for measuring the frequency-dependent second-order response using ultrabroadband strongly chirped laser pulses. The dispersion suppresses nonlinear frequency mixing, hence the second-order response of a material can be unambiguously retrieved. We demonstrate this method by measuring the frequency-dependent second-harmonic (SH) response of the metals gold, aluminium, silver, and copper in the wavelength range of about 900-1150 nm and compare the results to classical SH spectroscopy. The SH spectra indicate that interband transitions in the metals influence the overall nonlinear optical response.
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OBJECTIVE: To observe the effect of Yupingfeng San (YPFS) against OVA-induced allergic asthma in mice. METHOD: Mice were injected with OVA to establish the allergic asthma model. They were abdominally injected with 20 microg OVA on day 0 and 14, and inhaled aerosol 0.5% OVA solution for 20 min for seven days. The blank control group was administrated with equal volume of saline. YPFS groups with different doses were administrated intragastrically with YPFS every day, with the crude drug dosage of 3.25, 6.5, 13 g x kg(-1), respectively. The model group and control group were administrated with equal volume of saline. The positive control group was given intraperitoneally injected with 1 mg x kg(-1) DEX since aerosol inhalation. Blood was drawn after the last OVA aerosol inhalation to count the number of Eosnophils (Eos) in blood and detect IgE in serum; BALF was collected to count the number of cells and classify; right lung tissues were evenly grinded to detect cytokines IL-4 and IFN-gamma, and left upper lung lobes were collected for pathologic histology. RESULT: The level of Eos and IgE in serum increased significantly in the model group, and a large number of Eos were detected in BALF. Histopathological changes in lung showed bronchial serous exudation, tubular epithelial cells exfoliation, tube narrowing, widened alveolar septum, and bronchial periarterial lymphocytes infiltration. Homogenate of lung tissues showed increase of IL-4, and decrease in IFN-gamma/IL-4 ratio. YPFS groups with different doses displayed decrease of Eos in blood and BALF and IgE content in serum, and relief of pathologic changes in above models. Meanwhile, IL-4 content in homogenate of lung tissues decreased, with the increase in IFN-gamma/IL-4 ratio. CONCLUSION: YPFS shows the inhibitory effects on OVA-induced allergic asthma, involving down regulation of Eos and IgE levels in blood of asthma mice, and infiltration of inflammatory cells in lung tissues. Meanwhile, it can reduce IL-4 in lung homogenates, increase IFN-gamma/IL-4, and inhibits Th2 polarization.
Subject(s)
Asthma/drug therapy , Drugs, Chinese Herbal/administration & dosage , Animals , Asthma/chemically induced , Asthma/immunology , Disease Models, Animal , Eosinophils/drug effects , Eosinophils/immunology , Humans , Interferon-gamma/immunology , Interleukin-4/immunology , Male , Mice , Mice, Inbred BALB C , Ovalbumin/adverse effectsABSTRACT
We demonstrated an erbium-doped mode-locked fiber laser using a single-walled carbon nanotube-dispersed polyimide (SWNT-PI) film. Different mode-locking operations were compared and analyzed utilizing SWNT-PI films with different concentrations (2, 1, and 0.25 wt.%, respectively). It was found that the continuous single-pulse mode-locking operation was often accompanied by a continuous wave oscillation part for the 1 and 0.25 wt.% SWNT-PI films, whereas the 2 wt.% SWNT-PI film presented the most excellent mode-locking performance, thanks to sufficient modulation depth. Using the 2 wt.% SWNT-PI film, a stable pulse train with a pulse width of 840 fs and a repetition rate of 15.3 MHz was achieved. The average output power was 0.33 mW at the pump power of 155 mW under an output coupling ratio of 10%. Operational performance of the laser cavity when employing the 2 wt.% SWNT-PI film was also demonstrated.