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Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood-brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/ß-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain-blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/ß-catenin pathway.
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Dopamina , Miastenia Gravis , Humanos , Ratos , Animais , Dopamina/metabolismo , Células Endoteliais/metabolismo , Encéfalo , Barreira Hematoencefálica/metabolismo , Via de Sinalização Wnt/fisiologia , Miastenia Gravis/metabolismoRESUMO
As one of the directions of optical levitation technology, the mass measurement of micro-nano particles has always been a research hotspot in extremely weak mechanical measurements. When nanoscale particles are trapped in an optical trap, parameters such as density, diameter, and shape are unknown. Here we propose what we believe to be a new method to measure mass by fitting particle motion information to the Maxwell speed distribution law, with an accuracy better than 7% at 10 mbar. This method has the characteristics of requiring no external driving force, no precise natural frequency, no prior information such as density, and non-destructive testing within the medium vacuum range. With the increasing iterations, the uncertainty of mass measurement is reduced, and the accuracy of mass measurement of levitated particles is verified under multiple air pressures. It provides what we believe is a new method for the future non-destructive testing of nanoscale particles, and provides an apparently new way for the sensing measurement and metrology application fields of levitation dynamics systems.
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For an interferometric fiber-optic gyroscope (IFOG), the angle random walk, which represents the sensitivity of rotation detection, is mainly limited by the relative intensity noise (RIN) of a broadband source. Using a single-mode fiber ring resonator (SM-FRR) to filter the spectrum of a broadband light source is a common strategy for reducing the RIN at the proper IFOG frequency. However, this method depends on the polarization cross-coupling within the SM-FRR. We model the effect of polarization cross-coupling on the SM-FRR. Then, to further reduce the RIN, we introduce a polarization-maintaining fiber ring resonator (PM-FRR), which mitigates the effect of polarization cross-coupling on the SM-FRR. Using the PM-FRR as a spectrum filter, the RIN is reduced to -143â dB/Hz, with a reduction ratio of 25â dB, and the angle random walk in the IFOG is improved by over five times from 1.17 to 0.223 mdeg/h1/2 using a 2.1â km sensing coil.
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We presented faster and more accurate simulations and experiments describing the revolution of a suspended particle in optical tweezers under a low pressure. Instead of the state-of-the-art offline method of pinhole alignment, we proposed an in situ method of revolution suppression by adjusting the laser beam while observing the power spectral density and time-domain plot of the particle centroid displacement. The experimental results under different air pressures show that our method is more effective at low pressures. We observed that "revolution occurs when radial alignment error is below the threshold" and uncovered the mechanism behind this phenomenon. The rapidly growing Q value of the revolution indicates a high-precision resonance measurement method under lower air pressure compared with random translation measurements.
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Optical trapping of single nanoparticles in vacuum has various applications in both precise measurements and fundamental physics. However, to date, the number and size of randomly loaded nanoparticles in an optical trap is difficult to determine unless in vacuum. In this Letter, an efficient method for nanoparticle size estimation in an optical tweezer system before the evacuation of air was proposed and demonstrated experimentally, using scattering light from levitated particles. The particle radii deduced from the scattering light power in our proposal and from the kinetic theory of particles in gas match well (with the differences of less than 10%). For sample particles with radii ranging within 50-100 nm, we also provide a preselection rule based on this method, where over half of the trapped particles are verified as single particles. Such a particle analysis method is applicable also for the size estimation of levitated diamond particles, gold particles, and other plasmonic particles and can be applied to discovering novel scattering effects.
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BACKGROUND: Venous malformations (VM) are common vascular malformations. Percutaneous injection of sclerosants into the lesion has become mainstream therapy. The most commonly used sclerosants are ethanol, polidocanol, bleomycin, and the like. But few articles have reported that sclerosants are more effective and safer. METHODS: We performed a search on Cochrane, Embase, PubMed, China National Knowledge Infrastructure, CBM, and Wan Fang databases of Controlled Trials (from January 1, 2010, launch up to April 10, 2019) reporting outcome of intralesional ethanol, polidocanol, and bleomycin injections in patients with VM (n ≥ 20). A meta-analysis was conducted using Rev-man 5.3 software. RESULTS: A total of 9 articles, 632 participants and 676 lesions were included. Quality of evidence was generally low. Meta-analysis showed that absolute ethanol treatment was better than polidocanol in treating VM (p = .001), and absolute ethanol elicited a better response than bleomycin (p = .01). Ethanol therapeutic effect was not statistically significant compared with ethanol alone (p = .07), but the combination effect was better than polidocanol (p = .04). Ethanol treatment showed significantly more adverse reactions than polidocanol and combination therapy. CONCLUSION: Absolute ethanol combined with polidocanol is more effective in treating VM and has fewer adverse reactions.
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Etanol/administração & dosagem , Polidocanol/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Malformações Vasculares/tratamento farmacológico , Veias/anormalidades , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Etanol/efeitos adversos , Humanos , Injeções Intravenosas , Polidocanol/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Soluções Esclerosantes/efeitos adversos , Resultado do Tratamento , Veias/efeitos dos fármacosRESUMO
To investigate the efficacy and safety of combined therapy with adrenergic beta-antagonist and lasers in infantile hemangiomas (IH). A search of Pubmed, Cochrane, Embase, Wanfang Date, CNKI (China National Knowledge Infrastructure) and CBM (China Biology Medicine) databases was conducted to identify studies that examined response to combined therapy with adrenergic beta-antagonist and laser in IH patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) in random-effects or fixed-effects models were calculated with Review Manger 5.3. Efficacy of combined therapy with oral propranolol and lasers was significantly better than that of propranolol (OR 5.79, 95% CI 2.52-13.31, P < 0.00001) or lasers (OR 5.09, 95% CI 3.04-8.54, P < 0.00001) alone. Combined therapy with topical timolol and lasers was more effective than topical timolol (OR 3.71, 95% CI 2.46-5.59, P < 0.00001) or lasers (OR 10.92, 95% CI 1.90-62.70, P = 0.007) alone. We did not observe statistically significant differences of adverse reactions between combined therapy with oral propranolol and lasers and propranolol (OR 1.09, 95% CI 0.64-1.84, P = 0.75) or lasers (OR 0.83, 95% CI 0.28-2.50, P = 0.74). The incidence of adverse reactions in combined therapy with topical timolol and lasers and monotherapy with topical timolol therapy (OR 0.50, 95% CI 0.14-1.80, P = 0.75) or lasers (OR 0.29, 95% CI 0.06-1.55, P = 0.15) has no significant difference. The average treatment duration of combined therapy may be shorter than that of monotherapy. Combination therapy of adrenergic beta-antagonist and lasers on IH is significantly more effective than monotherapy, while the safety of combination therapy was not significantly higher than that of monotherapy.
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Antagonistas Adrenérgicos beta/uso terapêutico , Hemangioma Capilar/terapia , Terapia a Laser/métodos , Neoplasias Cutâneas/terapia , Terapia Combinada , Humanos , LactenteRESUMO
As a kind of ultra-sensitive acceleration sensing platform, optical tweezers show a minimum measurable value inversely proportional to the square of the diameter of the levitated spherical particle. However, with increasing diameter, the coupling of the displacement measurement between the axes becomes noticeable. This paper analyzes the source of coupling in a forward-scattering far-field detection regime and proposes a novel method of suppression. We theoretically and experimentally demonstrated that when three variable irises are added into the detection optics without changing other parts of optical structures, the decoupling of triaxial displacement signals mixed with each other show significant improvement. A coupling detection ratio reduction of 49.1 dB and 22.9 dB was realized in radial and axial directions, respectively, which is principally in accord with the simulations. This low-cost and robust approach makes it possible to accurately measure three-dimensional mechanical quantities simultaneously and may be helpful to actively cool the particle motion in optical tweezers even to the quantum ground state in the future.
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High precision fiber-optic gyroscopes (FOGs) interrogated with broadband light have angular random walk (ARW) limited by the source relative intensity noise (RIN). A passive fiber ring resonator (passive FRR) reduces the RIN and improves the ARW, but the low power transmission results in a low signal-to-noise ratio at the detection. For a great ARW improvement, the fiber ring resonator should have not only a great RIN reduction but also a large power transmission. An erbium-doped fiber amplifier (EDFA) is inserted in the passive resonator to construct an active fiber ring resonator (active FRR). The EDFA compensates for the loss of the resonator and leads to a high finesse and a greater reduction in the RIN. The coupling ratios of the couplers in the active FRR are both 50%-50% tap. By adjusting the EDFA gain properly, a 17-dB decrease in the RIN is demonstrated, which reduces the standard deviation by 8.5 dB. Adding the active FRR between the Sagnac interferometer and the broadband light, the detected power reaches 150 µW with the FOG at rest and without modulation, which is about one hundred times of the detected power when using a passive FRR. The phase noise is reduced by 6 dB at the proper frequency. The ARW is improved by 4.9 dB from 1.40 to 0.45 mdeg/hour1/2.
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The eigen frequency is a key parameter of a fiber optic gyroscope (FOG). We present an online eigen frequency tracking method for FOG technology based on the staircase waveform and a four-step frequency perturbation. Results show that the measurement accuracy of the eigen frequency does not exceed 1.7 Hz for a temperature range of 27.5°C-62.5°C and a variation rate of 0.24°C/min. This is in good agreement with the theoretical model. The method, which exhibits a low time-space complexity, simply requires the addition of a low-rate digital-to-analog converter to the existing gyro system. There is no requirement for the type of staircase waveform in the phase modulation, and the staircase waveform remains unchanged. Thus, this method can be easily transplanted into other algorithms.
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OBJECTIVE: To explore the role of progesterone in the pathogenesis and development of hemangioma in nude mice.â© Methods: The hemangioma model was established. Progesterone was injected intramuscularly at different doses (0.2, 0.4, and 0.8 mg/d) for one week. Camellia oil (0.4 mL/d) was injected intramuscularly as control. The size of hemangioma was observed dynamically. The subcutaneous implants were harvested on the 14th and 28th days. The expression of vascular endothelial growth factor in the tumor tissues were evaluated using immunohistochemistry and microvessel density (MVD) was counted under the microscope.â© Results: On the 14th day, the expression of vascular endothelial growth factor (P<0.01 and P<0.05, respectively) was higher, the volume of tumors (All P<0.01) and MVD (All P<0.01) were greater in the high-dose progesterone group than those in the control and low-dose progesterone group. On the 28th day, there was no significant difference in the volume of tumors among 4 groups (P>0.05). The expression of vascular endothelial growth factor (P<0.01) was lower, and MVD (All P<0.05) were less in the middle-dose and high-dose progesterone group than those in the control and low-dose progesterone group.â© Conclusion: Progesterone promotes angiogenesis via upregulation of vascular endothelial growth factor expression, promotion of hemangiomas proliferation, suggesting that excessive progesterone supplementation may be one of the initial factors for early hemangioma formation.
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Hemangioma , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica , Progesterona , Fator A de Crescimento do Endotélio VascularRESUMO
A method of improving the angular random walk (ARW) of a fiber optic gyroscope (FOG) using a fiber ring resonator (FRR) to reduce the relative intensity noise (RIN) is demonstrated. An FRR reduces the RIN near the proper frequency and improves the ARW. The analytical forms for the RIN transfer function and the power transmission of the FRR are derived when the free spectral range of the FRR is much narrower than the source bandwidth. Building the FRR using couplers and fiber with low excess loss enhances the RIN reduction. For the coupling ratios, there is a trade-off between the RIN reduction and the power transmission. The coupling ratios are 90%-10% tap in the experiment. When the FRR resonator length is shorter than the FOG coil length, the ARW improvement is further enhanced by adjusting the average window length in the signal processing. An experiment demonstrated a 7 dB decrease in the RIN at the loop proper frequency, which reduces the standard deviation by 3.5 dB. The ARW was reduced from 970 to 570 µdeg/h1/2, which amounts to a 2.3 dB reduction.
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Levitated micro-resonators in vacuums have attracted widespread attention due to their application potential in precision force sensing, acceleration sensing, mass measurement and gravitational wave sensing. The optically levitated microsphere in a counter-propagating dual-beam optical trap has been of particular interest because of its large measurement range and flexible manipulation. In this system, laser intensity fluctuation directly influences the trap stability and measurement sensitivity, which makes it a crucial factor in improving trapping performance. In this paper, a time-varying optical force (TVOF) model is established to characterize the influence of laser intensity fluctuation in a dual-beam optical trap. The model describes the relationship between the laser intensity fluctuation, optical force and the dynamic motion of the micro-sized sphere. In addition, an external laser intensity control method is proposed, which achieved a 16.9 dB laser power stability control at the relaxation oscillation frequency. The long-term laser intensity fluctuation was suppressed from 3% to 0.4% in a one-hour period. Experiments showed that the particle's position detection sensitivity and the stability of the relaxation oscillation could be improved by laser intensity fluctuation suppression.
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Myasthenia gravis (MG) is characterized by fatigable skeletal muscle weakness with a fluctuating and unpredictable disease course and is caused by circulating autoantibodies and pathological T helper cells. Regulation of B-cell function and the T-cell network may be a potential therapeutic strategy for MG. MicroRNAs (miRNAs) have emerged as potential biomarkers in immune disorders due to their critical roles in various immune cells and multiple inflammatory diseases. Aberrant miR-146a signal activation has been reported in autoimmune diseases, but a detailed exploration of the relationship between miR-146a and MG is still necessary. Using an experimental autoimmune myasthenia gravis (EAMG) rat model, we observed that miR-146a was highly expressed in the spleen but expressed at low levels in the thymus and lymph nodes in EAMG rats. Additionally, miR-146a expression in T and B cells was also quite different. EAMG-specific Th17 and Treg cells had lower miR-146a levels, while EAMG-specific B cells had higher miR-146a levels, indicating that targeted intervention against miR-146a might have diametrically opposite effects. Metformin, a drug that was recently demonstrated to alleviate EAMG, may rescue the functions of both Th17 cells and B cells by reversing the expression of miR-146a. We also investigated the downstream target genes of miR-146a in both T and B cells using bioinformatics screening and qPCR. Taken together, our study identifies a complex role of miR-146a in the EAMG rat model, suggesting that more caution should be paid in targeting miR-146a for the treatment of MG.
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Metformina , MicroRNAs , Miastenia Gravis Autoimune Experimental , Receptores Colinérgicos/imunologia , Animais , Autoanticorpos , Linfócitos B , Biomarcadores , Metformina/farmacologia , Metformina/uso terapêutico , MicroRNAs/genética , Miastenia Gravis Autoimune Experimental/tratamento farmacológico , Miastenia Gravis Autoimune Experimental/genética , Ratos , Células Th17RESUMO
This study investigates the propagation properties and radiation forces on Rayleigh dielectric particles produced by novel sine-modulated Gaussian beams (SMGBs) because of the unique focusing properties of four independent light intensity distribution centers and possessing many deep potential wells in the output plane of the target laser. The described beams can concurrently capture and manipulate multiple Rayleigh dielectric spheres with high refractive indices without disturbing each other at the focus plane. Spheres with a low refractive index can be guided or confined in the focus but cannot be stably trapped in this single beam trap. Simulation results demonstrate that the focused SMGBs can be used to trap particle in different planes by increasing the sine-modulate coefficient g. The conditions for effective and stable capture of high-index particles and the threshold of detectable radius are determined at the end of this study.
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The focusing properties of elegant third-order Hermite-Gaussian beams (TH3GBs) and the radiation forces exerted on dielectric spherical particles produced by such beams in the Rayleigh scattering regime have been theoretically studied. Numerical results indicate that the elegant TH3GBs can be used to simultaneously trap and manipulate nanosized dielectric spheres with refractive indexes lower than the surrounding medium at the focus and those with refractive indexes larger than the surrounding medium in the focal vicinity. Furthermore, by changing the radius of the beam waist, the transverse trapping range and stiffness at the focal plane can be changed.