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Infantile bullous pemphigoid (BP) is a rare autoantibody-mediated skin disorder. We report the effective treatment of a 6-month-old infant with BP using baricitinib, a Janus kinase (JAK) inhibitor, after failure with steroids and intravenous immunoglobulin. The patient achieved full remission and discontinued all medications without any relapses. To our knowledge, this is the first case of baricitinib used in an infant with BP.
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We demonstrate the direct generation of single-frequency switchable orbital angular momentum (OAM) modes in a 1â µm wavelength range using a Nd:YVO4 microchip laser. The 808â nm laser diode pump beam is shaped into annular through an axicon associated with a lens. By adjusting the diameter and power of the annular pump beam, various OAM modes with different mode volumes can oscillate inside the Nd:YVO4 microchip. Moreover, a single-frequency output is also available due to the short cavity of the microchip. In the proof-of-principle experiment, single-frequency twofold multiplexed OAM modes | ± 1> and | ± 2> are generated, with experimentally measured fidelity higher than 96%. This work presents a compact and versatile single-frequency OAM source and will inspire multiple advanced scenarios ranging from classical to quantum photonics.
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Transponder-type laser interferometry is essential in spaceborne gravitational wave detection missions. This paper presents a transponder-type laser interferometer prototype for potential noise calibration of spaceborne gravitational wave detectors. Using a digital optical phase-locked loop, we successfully locked the phase of the slave laser to the master laser (â¼200p W). Once the link between the master laser and the slave laser is established, the two satellites (essentially two lasers) form a transponder-type laser interferometer. We carefully analyze the measurement stability and noise characteristics of the interferometer, and the results show that the Allan deviation of the zero drift can reach 243.2 pm at t=0.429s, while the noise spectral density has a typical 1/f line shape with a floor of 21p m/H z 1/2 at 1 Hz. The coherence analysis shows that the temperature drift is an important factor limiting the performance of the interferometer below 2 mHz, while the frequency noise of the master laser is not dominant in the experiment. Transponder-type laser interferometers have a wide range of applications in intersatellite communication and measurement. Our design can serve as a valuable reference for gravitational wave detection missions such as LISA.
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Construction of laser heterodyne interferometric bench to measure tiny translation and tilt with picometer- and nanoradian-level sensitivity in the millihertz band is critical for the success of spaceborne gravitational wave detection, including the LISA, Taiji, and Tianqin missions. In this paper, we report on the construction and testing of a laser heterodyne interferometric bench that contains two optical path designs, the dual-beam heterodyne interferometry and the polarization-multiplexing heterodyne interferometry. The measurement sensitivity of translation and tilt reaches below 3 pm/Hz1/2 and 12 nrad/Hz1/2 for frequencies above 10 mHz, respectively. As a technical verification platform, stabilization loops of amplitude and phase and coherence analysis are also conducted through the bench. Furthermore, we demonstrate initial implements of phase-locking technology and multiple degree of freedom measurements as the extended applications of the constructed bench. The achieved results show that the laser interferometric bench would serve as an excellent experimental platform for the technology demonstration and verification of future Chinese spaceborne gravitational wave detection.
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In this article, we demonstrate an improved efficient fibre sensor with a high sensitivity to measure glucose concentrations in the physiological range of human beings, operating in a broad spectral bandwidth from the near- to mid-infrared. The sensor consists of a dual-peak long period grating (DPLPG) with a period of 150 µm inscribed in an optical fibre with a diameter of 80 µm. The investigation of sensing for refractive index results in a sensitivity of ~-885.7 nm/refractive index unit (RIU) and ~2008.6 nm/RIU in the range of 1.30-1.44. The glucose measurement is achieved by the immobilisation of a layer of enzyme of glucose oxidase (GOD) onto the fibre surface for the selective enhancement of sensitivity for glucose. The sensor can measure glucose concentrations with a maximum sensitivity of -36.25 nm/(mg/mL) in the range of 0.1-3.0 mg/mL. To the best of our knowledge, this is the highest sensitivity ever achieved for a measurement of glucose with a long period grating-based sensor, indicating its potential for many applications including pharmaceutical, biomedical and food industries.
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Técnicas Biossensoriais , Humanos , Técnicas Biossensoriais/métodos , Fibras Ópticas , Refratometria , Glucose , Glucose OxidaseRESUMO
This study describes the design and performance of a deflection-type refractometer based on measuring the fringe shift from the Fresnel diffraction pattern to solve some major limitations of conventional differential refractometers, such as measurement range, resolution, zero balancing, and monitoring analysis. The refractometer apparatus comprises a coherent light source, linear Fresnel zone plate, measuring cell, and image capture device mounted on a movable platform. The distance measurement unit is configured to detect fringe deflection due to the difference in refractive index between the sample and the reference. To achieve this, distance measurements with an accuracy of a few nanometers by using the local frequency method and fringe shift measurement method are quite feasible. The uncertainty in this technique is determined by the smallest change in the longitudinal displacement of the image for which the CCD camera can detect a change in pixel position. The refractive index is obtained with a highly extended measurement range of at least ±0.4R I U and precision of the order of 2×10-4 R I U. A numerical comparison between computer simulation of the diffraction patterns that occur when the linear Fresnel zone plate is illuminated by a plane light traveling parallel to the z axis.
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We developed a digital optical phase-locking loop (DOPLL) for weak light phase locking in spaceborne gravitational wave interferometers (SGWIs). Using the system, we successfully locked the phase of the slave laser to the master laser with the power of only several picowatts, much smaller than the LISA requirement (100 pW). The system does not introduce steady-state errors, and the Bode diagram shows its stability. The out-loop phase noise floor (2.3×10-4 and 5.2×10-4 r a d/H z 1/2) is very close to the shot noise limit. The Allan standard deviation of the heterodyne signal reaches 3.1×10-17 at 1000 s. With the previous automatic locking program designed by other researchers, the results demonstrate that DOPLLs have bright application prospects and can be applied in the transducer of the SGWI.
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Developing an ultrasensitive and reliable device for continuous monitoring of various endocrine-disrupting chemicals (EDCs) is in high demand, yet it remains a significant challenge. Traditional label-free surface plasmon resonance (SPR) sensing relies on the interaction of the surface plasmon wave and the sensing liquid via intensity modulation, endowed with simple structure and easy-to-miniaturization, however suffering from inferior sensitivity and stability. Here, we propose a novel optical structure in which the frequency-shifted light of different polarization returned to the laser cavity to stimulate laser heterodyne feedback interferometry (LHFI), hence amplifying the reflectivity change caused by the refractive index (RI) variations on the gold-coated SPR chip surface, and the s-polarized light could be further used as a reference to compensate for the noise of the LHFI-amplified SPR system, resulting in nearly three orders of magnitude enhancement of the RI sensing resolution (5.9 × 10-8 RIU) compared to the original SPR system (2.0 × 10-5 RIU). To further boost intense signal enhancement, custom-designed gold nanorods (AuNRs), which were optimized by the finite-difference time-domain (FDTD) simulation, were used to generate localized surface plasmon resonance (LSPR). By exploiting the estrogen receptor as the recognition material, estrogenic active chemicals were detected with a 17ß-estradiol/L detection limit of 0.004 ng, which is nearly 180-fold lower than that of the system without introducing AuNRs. The developed SPR biosensor is expected to be capable of screening various EDCs with universality by using several nuclear receptors, such as the androgen receptor and thyroid receptor, and will substantially accelerate the assessment of global EDCs.
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Técnicas Biossensoriais , Disruptores Endócrinos , Ressonância de Plasmônio de Superfície/métodos , Disruptores Endócrinos/análise , Retroalimentação , Técnicas Biossensoriais/métodos , Ouro/químicaRESUMO
Simple yet ultrasensitive and accurate quantification of a variety of analytical targets by virtue of a universal sensing device holds promise to revolutionize environmental monitoring, medical diagnostics, and food safety. Here, we propose a novel optical surface plasmon resonance (SPR) system in which the frequency-shifted light of different polarizations returned the laser cavity to stimulate laser heterodyne feedback interferometry (LHFI), hence amplifying the reflectivity change caused by the refractive index (RI) variations on the gold-coated SPR chip surface. In addition, the s-polarized light was further used as the reference to compensate the noise of the LHFI-amplified SPR system, resulting in nearly 3 orders of magnitude enhancement of RI resolution (5.9 × 10-8 RIU) over the original SPR system (2.0 × 10-5 RIU). By exploiting nucleic acids, antibodies, and receptors as recognition materials, a variety of micropollutants were detected with ultralow detection limits, ranging from a toxic metal ion (Hg2+, 70 ng/L) to a group of commonly occurring biotoxin (microcystins, 3.9 ng microcystin-LR/L) and a class of environmental endocrine disruptors (estrogens, 0.7 ng 17ß-estradiol/L). This sensing platform exhibits several distinct characteristics, including dual improvement of sensitivity and stability and common-path optical construction without needing optical alignment, demonstrating a promising avenue toward environmental monitoring.
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Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Ressonância de Plasmônio de Superfície/métodos , Luz , OuroRESUMO
BACKGROUND AND PURPOSE: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism. EXPERIMENTAL APPROACH: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients. KEY RESULTS: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. CONCLUSION AND IMPLICATIONS: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.
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Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Prurido/tratamento farmacológico , Pele/patologia , Inflamação/patologia , Células Receptoras SensoriaisRESUMO
We propose an improved opposition-based self-adaptive differential evolution (IOSaDE) algorithm for multi-parameter optimization in vibrational hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (CARS) thermometry. This new algorithm self-adaptively combines the advantages of three mutation schemes and introduces two opposite population stages to avoid premature convergence. The probability of choosing each mutation scheme will be updated based on its previous performance after the first learning period. The IOSaDE method is compared with nine other traditional differential evolution (DE) methods in simulated spectra with different simulation parameters and experimental spectra at different probe time delays. In simulated spectra, both the average and standard deviation values of the final residuals from 20 consecutive trials using IOSaDE are more than two orders of magnitude smaller than those using other methods. Meanwhile, the fitting temperatures in simulated spectra using IOSaDE are all consistent with the target temperatures. In experimental spectra, the standard deviations of the fitting temperatures from 20 consecutive trials decrease more than four times by using IOSaDE, and the errors of the fitting temperatures also decrease more than 18%. The performance of the IOSaDE algorithm shows the ability to achieve accurate and stable temperature measurement in CARS thermometry and indicates the potential in applications where multiple parameters need to be considered.
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Objective: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support may have cerebral hemodynamic changes whose impact on patient outcome are not fully elucidated. This study aims to evaluate the correlation between cerebral hemodynamic changes and prognostic outcome in patients during VA-ECMO. Methods: Transcranial Doppler (TCD) ultrasound examination was performed to attain the systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), and pulsatility index (PI) of patients undergoing VA-ECMO. Cardiac ultrasound was also performed to assess the correlation between the left ventricular outflow tract velocity time integral (LVOT VTI), left ventricular ejection fraction (LVEF), and middle cerebral artery (MCA) with the systolic peak. Moreover, we assessed the predictive value of LVOT VTI and LVEF in patients with the systolic peak. Patients were divided into survival and death groups according to the 28-day survival period. Clinical data were compared between the two groups to investigate the effects of cerebral hemodynamic changes on the prognosis of VA-ECMO patients. Results: We found that the patient's LVOT VTI and LVEF had high predictive values for the systolic peak of the right middle cerebral artery. The initial LVEF, Vs, Vd and PI, and lactate level as well as the MODS incidence rate difference were significantly different between the survival and death groups. In addition, the results showed that the initial Vs value was an independent risk factor for the prognosis of patients undergoing VA-ECMO. Conclusions: Cerebral hemodynamic changes may occur in patients supported by VA-ECMO. In addition, a poor cerebral arterial pulsatile blood flow was closely correlated with an unfavorable outcome in these patients.
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Ultrassonografia Doppler Transcraniana , Função Ventricular Esquerda , Circulação Cerebrovascular/fisiologia , Hemodinâmica , Humanos , Volume SistólicoRESUMO
The development of high-temperature photodetectors can be beneficial for numerous applications, such as aerospace engineering, military defence and harsh-environments robotics. However, current high-temperature photodetectors are characterized by low photoresponsivity (<10 A/W) due to the poor optical sensitivity of commonly used heat-resistant materials. Here, we report the realization of h-BN-encapsulated graphite/WSe2 photodetectors which can endure temperatures up to 700 °C in air (1000 °C in vacuum) and exhibit unconventional negative photoconductivity (NPC) at high temperatures. Operated in NPC mode, the devices show a photoresponsivity up to 2.2 × 106 A/W, which is ~5 orders of magnitude higher than that of state-of-the-art high-temperature photodetectors. Furthermore, our devices demonstrate good flexibility, making it highly adaptive to various shaped surfaces. Our approach can be extended to other 2D materials and may stimulate further developments of 2D optoelectronic devices operating in harsh environments.
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Xanthoma pathogenesis is speculated to be associated with oxidized low-density lipoprotein (ox-LDL) deposition, although this remains unclear. Most patients with diffuse plane xanthomas present elevated blood lipid levels, and they benefit from treatment with oral lipid-lowering agents. However, there is no available treatment for diffuse normolipemic plane xanthoma (DNPX). In this study, for the first time, we used a topical simvastatin ointment to treat DNPX in three pediatric patients and observed favorable results. Immunofluorescence staining showed that the pyroptotic pathway was significantly attenuated after topical simvastatin application on the skin lesions of the patients. As ox-LDL deposition was observed in the lesions, we used ox-LDL to build a foam cell model in vitro. In the ox-LDL-induced foam cell formation, simvastatin consistently inhibited pyroptotic activation and inflammation in the macrophages. Additionally, the overexpression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), the known target of statins, reversed the effects of simvastatin. Moreover, gasdermin D (GSDMD) or HMGCR knockdown inhibited ox-LDL-induced pyroptosis. Furthermore, the immunoprecipitation results confirmed the interaction between NLRP3 and HMGCR, and this interaction was inhibited by simvastatin. In conclusion, we demonstrated that topical application of simvastatin ointment might be a promising treatment for DNPX skin lesions and that this therapeutic effect may be related to pyroptosis inhibition via HMGCR inhibition in foam cells. Moreover, xanthoma pathogenesis might be associated with ox-LDL deposition and inflammation.
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Células Espumosas , Xantomatose , Criança , Células Espumosas/metabolismo , Humanos , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pomadas/metabolismo , Piroptose , Sinvastatina/farmacologia , Xantomatose/tratamento farmacológico , Xantomatose/metabolismoRESUMO
The ongoing outbreak of the COVID-19 has highlighted the importance of the pandemic prevention and control. A rapid and sensitive antigen assay is crucial in diagnosing and curbing pandemic. Here, we report a novel surface plasmon resonance biosensor based on laser heterodyne feedback interferometry for the detection of SARS-CoV-2 spike antigen, which is achieved by detecting the tiny difference in refractive index between different antigen concentrations. The biosensor converts the refractive index changes at the sensing unit into the intensity changes of light through surface plasmon resonance, achieving label-free and real-time detection of biological samples. Moreover, the gain amplification effect of the laser heterodyne feedback interferometry further improved the sensitivity of this biosensor. The biosensor can rapidly respond to continuous and periodic changes in the refractive index with a high resolution of 3.75 × 10-8 RIU, demonstrating the repeatability of the biosensor. Afterwards, the biosensor is immobilized by the anti-SARS-CoV-2 spike monoclonal antibodies, thus realizing the specific recognition of the antigen. The biosensor exhibited a high sensitivity towards the concentration of the antigen with a linear dynamic range of five orders of magnitude and a resolution of 0.08 pg/mL. These results indicate that this principle can be used as a rapid diagnostic method for COVID-19 antigens without sample labelling.
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Técnicas Biossensoriais , COVID-19 , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , Retroalimentação , Humanos , Lasers , SARS-CoV-2 , Ressonância de Plasmônio de Superfície/métodosRESUMO
A novel, to the best of our knowledge, interferometry based on the laser feedback technique with long transmission distance is proposed. The system has the advantages of high sensitivity for uncooperative targets and a simple structure. Also, the quasi-common path orthogonally polarized light compensation method is designed to compensate for the drift in long-distance transmission and achieves more than 200 times reduction experimentally. Using a copper block as a target, the displacement resolution of 20 nm is demonstrated experimentally with 300 m transmission distance. The sub-microwatt power consumption of the measurement beam indicates the high sensitivity of the interferometry. The performance, in terms of linearity, is also evaluated. Although a lot needs to be improved, the proposed method is promising for further development toward practical applications, like sensors in remote, nuclear radiative, or other harsh conditions.
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In this paper, the phase response of fiber Fabry-Pérot cavity-based fiber optic microphones (FFPC-FOMs) is discussed through an analysis of the results of simulation and experiments. The phase difference of FFPC-FOMs mainly originates from two aspects: different phase lags of the mechanical-acoustic systems and different quadrature working points (Q*) on interference curves. The former is analyzed by an impedance-type analogous circuit, and the simulation results reveal that the change in cavity length and resonance frequency in a large range have an insignificant influence on the phase difference. The latter shows a unique effect on the phase difference and causes the phase of FFPC-FOMs to be either in or out of phase. The phase differences of four samples of FFPC-FOMs with different cavity lengths and resonance frequencies are measured in the frequency range 50 Hz-4 kHz. Experimental results of the phase difference are well consistent with simulation results. All samples of FFPC-FOMs can be divided into two groups: one is near 0° and the other is near 180°. In addition, the FFPC-FOMs in each group have good phase consistency for the array applications.
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A novel method of ultrasound-modulated optical tomography (UOT) detection based on the laser feedback technology is proposed in this Letter. The system has advantages such as a simple structure, high sensitivity, and reflective configuration. Effective penetration depths of up to 9 cm and 5 cm in phantom and biological tissues, respectively, have been demonstrated experimentally. The detection capability is comparable with the state of the art in the transmission mode but with a much lower photon consumption. Although a lot remains to be improved, the proposed method is promising for further development toward practical applications.
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Spin rate of a high-speed spinning-rotor gyroscope will make a significant impact on angular rate sensor performances such as the scale factor, resolution, measurement range, and bias stability. This paper presents the spin rate effects on performance indicators of a microelectromechanical systems (MEMS) gyroscope where a free-spinning rotor is electrostatically suspended in an evacuated vacuum cavity and functions as a dual-axis angular rate sensor. Theoretical models of the scale factor and measurement range of such a spinning-rotor gyroscope are derived. The experimental results indicate that the measured scale factors at different settings of the spin rate match well with the theoretical predication. In order to separate the disturbance component of the rotation control loop on the gyroscope output, a testing strategy is proposed by operating the gyroscope at different spin rates. Experimental results on a prototype gyroscope show that the squared drive voltage generated by the rotation control loop is approximately proportional to the noise of the gyroscope output. It was further investigated that an improved performance of such spinning-rotor gyroscopes can be achieved by operating the gyroscope rotor at an optimal spin rate.