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BACKGROUND: MicroRNA (miRNA)-processing machinery may modify the risk of primary Sjögren's syndrome (pSS) by altering miRNA expression profiles. Inflammatory cytokines and reactive oxygen species (ROS) are also involved in pSS; however, the role of altered miRNAs expression in its pathogenesis is still unclear. We aimed to evaluate the relationship between single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035), Dicer (rs3742330), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), and the risk of pSS in female patients. The potential associations of cytokines and ROS with pSS-susceptible SNPs were also evaluated. MATERIALS AND METHODS: The SNPs confirmed by polymerase chain reaction ligase detection reaction were genotyped in 74 female patients with pSS and 77 controls. The relationship was analyzed by Student's t-test, Wilcoxon rank-sum test, chi-square test, Pearson's correlation test, and binary logistic regression analysis. RESULTS: For rs197412 of the GEMIN3 gene, the genotype TT carrier was associated with a 2.172-fold increased risk for pSS when compared with that of CT+CC carrier (odds ratio: 2.172, 95% CI, 1.133-4.166, p=0.019). Simultaneously, the pSS-susceptible TT carriers were associated with increased interferon-γ (IFN-γ) (P < 0.001) and tumor necrosis factor-α (TNF-α) (P = 0.003) levels when compared with that of CT+CC genotype carriers in female patients with pSS. The subsequent analysis also showed a weak positive correlation between IFN-γ and TNF-α levels (r=0.271, P = 0.019). CONCLUSION: The predictors of GEMIN3 SNPs might modify pSS development in females by mediating the expression of miRNAs and therefore regulate the levels of IFN-γ and TNF-α.
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Understanding the mechanism of mode-locking in a laser with high-order transverse mode is important for achieving an ultrashort pulses train under more complicated conditions. So far, mode-locking with high-order transverse mode has not been reported in other lasers except the multimode fiber laser. This paper demonstrates robust mode-locking with high-order transverse mode in a Kerr-lens mode-locked vertical-external-cavity surface-emitting laser for the first time, to the best of our knowledge. While the longitudinal modes are locked, continuous mode-locking accompanied by high-order transverse mode up to TEM40 is observed. The threshold of the mode-locking is only a little bigger than that of the lasing. After the laser oscillation is built up, the mode-locked pulse train can be obtained almost immediately and maintained until the thermal rollover of the laser. Output powers of 717 mW under fundamental mode and 666 mW under high-order transverse mode are achieved with a 4.3 ps pulse duration and 1.1 GHz pulses repetition rate, and some phenomenological explanations to the related characteristics of the mode-locked operation of high-order transverse mode in the vertical-external-cavity surface-emitting laser are proposed.
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Advanced light sources in the blue-green band are crucial for underwater wireless optical communication (UWOC) systems. Vertical-external-cavity surface-emitting lasers (VECSELs) can produce high output power and good beam quality, making them suitable for UWOC. This paper presents a 108 m distance UWOC based on a 100 mW 490 nm blue VECSEL and an acousto-optic modulator (AOM). The high-quality beam, which is near diffraction-limited, undergoes relatively small optical attenuation when using a conventional avalanche photodiode (APD) as the detector and employing 64-pulse position modulation (PPM). At the time-slot frequency of 50 MHz, the bit error rate (BER) of the UWOC was 2.7 × 10-5. This is the first reported AOM-based UWOC system with a transmission distance over 100 m. The estimated maximum transmission distance may be improved to about 180 m by fully utilizing the detection accuracy of the APD according to the measured attenuation coefficient of the blue VECSEL used. This type of UWOC system, composed of a high-beam-quality light source and a conventional detector, make it more closely suited to practical applications.
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Semiconductor disk lasers can produce high output power and good beam quality simultaneously. The high intracavity circulating power of about hundreds of watts, along with the flexibility of tailorable emitting wavelengths, make it an attractive light source for obtaining ultraviolet (UV) radiation from near-infrared lasers through nonlinear frequency conversion. This work reports a frequency tripled 327â nm semiconductor disk laser with record output power and wavelength tuning range by using a type-I phase-matched LiB3O5 (LBO) crystal and a type-I phase-matched ß-BaB2O4 (BBO) crystal as the frequency-doubling and -tripling crystals respectively. Thanks to the obviously larger nonlinear coefficient of the type-I phase-matched BBO compared to the commonly used type-II phase-matched LBO, as well as the small spot size specifically designed at the crystal location, the maximum output power of UV lasers reaches 538â mW, corresponding to an optical-to-optical conversion efficiency from pump to UV laser of about 1.14%. A wavelength tuning range of about 8.6â nm and good power stability with a standard deviation of about 0.94 are also achieved.
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Realtime spectroscopy access to ultrafast fiber lasers provides new opportunities for exploring complex soliton interaction dynamics. In this study, we employ a time-stretch technique that enables real-time access to both spectral and temporal dynamics, revealing rich nonlinear processes in asynchronous dual wavelength mode-locked pulses in an ultrafast fiber laser. Due to the different group velocities of the two wavelengths, the mode-locked solitons centered at different wavelengths periodically collide with each other. We recorded the entire process of soliton establishment, stabilization, and disappearance, shedding light on the mystery of stable transmission of dual-wavelength mode-locked pulses. These processes were observed for the first time in an ultrafast fiber laser, and the experimental evidence provides important insights into the understanding of nonlinear dynamics in fiber lasers, as well as the potential for improving laser performance for application in dual-comb spectroscopy.
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BACKGROUND: Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients. METHODS: A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients. CONCLUSIONS: Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias Gástricas , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , alfa-Fetoproteínas , Neoplasias Gástricas/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms. METHODS: CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1). RESULTS: CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo. CONCLUSION: CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.
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Fibroblastos Asociados al Cáncer , Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Humanos , Ratones , Neoplasias de Cabeza y Cuello/metabolismo , Integrina beta1/genética , Metástasis Linfática/genética , Neoplasias de la Boca/metabolismo , Recurrencia Local de Neoplasia , Complejo Represivo Polycomb 1/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismoRESUMEN
Alzheimer's disease (AD) is considered to be the most common neurodegenerative disease, with clinical symptoms encompassing progressive memory loss and cognitive impairment. Necroptosis is a form of programmed necrosis that promotes cell death and neuroinflammation, which further mediates the pathogenesis of several neurodegenerative diseases, especially AD. Current evidence has strongly suggested that necroptosis is activated in AD brains, resulting in neuronal death and cognitive impairment. We searched the PubMed database, screening all articles published before September 28, 2022 related to necroptosis in the context of AD pathology. The keywords in the search included: "necroptosis", "Alzheimer's disease", "signaling pathways", "Aß", Aßo", "Tau", "p-Tau", "neuronal death", "BBB damage", "neuroinflammation", "microglia", "mitochondrial dysfunction", "granulovacuolar degeneration", "synaptic loss", "axonal degeneration", "Nec-1", "Nec-1s", "GSK872", "NSA", "OGA", "RIPK1", "RIPK3", and "MLKL". Results show that necroptosis has been involved in multiple pathological processes of AD, including amyloid-ß aggregation, Tau accumulation, neuronal death, and blood-brain barrier damage, etc. More importantly, existing research on AD necroptosis interventions, including drug intervention and potential gene targets, as well as its current clinical development status, was discussed. Finally, the issues pertaining to necroptosis in AD were presented. Accordingly, this review may provide further insight into clinical perspectives and challenges for the future treatment of AD by targeting the necroptosis pathway.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Necrosis , Apoptosis , Péptidos beta-AmiloidesRESUMEN
Liquid-phase exfoliation can be developed for the large-scale production of two-dimensional materials for photonic applications. Although atomically thin 2D transition metal dichalcogenides (TMDs) show enhanced nonlinear optical properties or photoluminescence quantum yield relative to the bulk phase, these properties are weak in the absolute sense due to the ultrashort optical path, and they are also sensitive to layer-dependent symmetry properties. Another practical issue is that the chemical stability of some TMDs (e.g., Weyl semimetals) decreases dramatically as the thickness scales down to monolayer, precluding application as optical components in air. To address these issues, a way of exfoliating TMDs that ensures instantaneous passivation needs to be developed. Here, we employed a polymer-assisted electrochemical exfoliation strategy to synthesize PVP-passivated TMDs monolayers that could be spin coated and restacked into organic-inorganic superlattices with well-defined X-ray diffraction patterns. The segregation of restacked TMDs (e.g., MoS2) by PVP allows the inversion asymmetry of individual layers to be maintained in these superlattices, which allows second harmonic generation and photoluminescence to be linearly scaled with thickness. PVP-passivated monolayer 1T'-MoTe2 saturable absorber fabricated from these flakes exhibits fast response and recovery time (<150 fs) and pulse stability. Continuous-wave mode-locking based on 1T'-MoTe2 saturable absorber in a fiber ring laser cavity has been realized, attaining a fundamental repetition rate of 3.15 MHz and pulse duration as short as 867 fs at 1563 nm.
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Based on mathematic simulations, the impact of spectral filtering on pulse breaking up and noise-like pulse generation in all-normal-dispersion fiber lasers are investigated. Three types of spectrum filters are employed in the simulations, which have a Gaussian-shaped profile, super-Gaussian-shaped profile, and sinusoidal-shaped profile, respectively. With the Gaussian-shaped filter, the pulse breaking-up process is discussed. The super-Gaussian-shaped filter and the sinusoidal-shaped filter have two different formation mechanisms for noise-like pulses and are revealed. In addition, with the sinusoidal-shaped filter, dissipative solitons of different central wavelengths are achieved.
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China's financial development boomed after the recent world financial crisis in 2007. Financial development may affect an economy and hence carbon emissions significantly. No research has examined their relationship since this crisis up to now. Against this background, the effect of financial development on carbon intensity in China from 2007 to 2016 is investigated. The spatial and temporal patterns, and the dynamic evolution of both China's provincial carbon emissions and financial development were firstly investigated. Then a Spatial Durbin Model was employed to explore the effects of financial development, since this crisis, on carbon intensity, controlling related variables. The results show that financial development will significantly increase the local province's emissions but significantly decrease adjacent areas' emissions to a larger extent, so that the overall effect is that financial development will curb carbon emissions. The paper concludes that carbon emission reductions in China since 2007 may not be caused by the financial resources being channeled into the research and development of emission-reduction technologies or into high value-added firms. Hence, it is suggested that measures be taken to channel financial resources into the right projects and firms.
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The polarization and threshold of distributed feedback (DFB) polymer lasers were controlled by adjusting the cavity coupling. The cavity of DFB polymer lasers consisted of two gratings, which was fabricated by a two-beam multi-exposure holographic technique. The coupling strength of the cavity modes was tuned by changing the angle between the two gratings. The threshold of the polymer lasers decreased with reducing the coupling strength of the cavity modes. A minimum threshold was observed at the lowest coupling strength. Moreover, the azimuthally polarized output of the polymer lasers was modified by changing the cavity coupling. These results may provide additional perspectives to improve the performance of DFB polymer lasers.
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We demonstrate the compression of noise-like pulses in an Yb-doped fiber master-oscillator power-amplifier (MOPA). The seed source of the MOPA is an NPR mode locked fiber laser delivering 5.94-ps dissipative soliton pulses with a repetition rate of 37.48 MHz. After amplification in the Yb-doped fiber amplifier, stable noise-like pulses with maximum power of 5 W are obtained. Subsequently a grating pair is used to tailor the spectrum and compensate the dispersion of the amplified noise-like pulses. The pedestal of de-convolution autocorrelation trace is compressed from 6.5 ps to 920 fs. To the best of our knowledge, this is the first time that the pedestal of a noise-like pulse is compressed to femtosecond region.
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We demonstrate noise-like pulses with a 14.5 fs spike generated in an Yb-doped fiber nonlinear amplifier after compression, while the pedestal has a width of 3.70 ps. This Yb-doped fiber nonlinear amplifier is seeded by dissipative solitons. With an average output power of 5 W, the single pulse energy is approximately 200 nJ at a repetition rate of 24.65 MHz. Mathematical research based on the coupled nonlinear Schrödinger equations about the generation and the compressibility of the noise-like pulses is also carried out.
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GaAs/AlAs distributed Bragg reflectors (DBRs) are widely used in the gain chips of 1 µm wave band semiconductor disk lasers (SDLs) as an end/folded cavity mirror. Because the generated redundant heat in the active region of a gain chip mainly dissipates through the DBR, thermal conductivities of DBRs are crucial for the output performance of SDLs. For the purpose of more reasonable semiconductor wafer design, to improve the thermal management of SDLs, accurate thermal conductivities of DBRs with various layer thicknesses are under considerable requirement. By the use of the equilibrium molecular dynamics (EMD) simulation and the Tersoff potential, thermal conductivities of GaAs/AlAs superlattices with different layer thickness are calculated, and computed results are compared with reported data to verify the validity of the EMD simulation. The computed thermal conductivities of GaAs/AlAs DBRs using the EMD method show significant reduction in contrast to the bulk value. Compared to EMD simulation, analytic methods result in smaller values of thermal conductivities and get close to the bulk value much more slowly with increasing layer thickness. In the layer thickness of interest (60-100 nm), the Matthiessen rule with α=1 for GaAs and α=0.5 for AlAs is a practicable tool for thermal conductivity estimation.
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We experimentally demonstrate a kind of simplified Yb-doped mode-locked fiber laser with a nonlinear polarization rotation technique. In the oscillator, there are no waveplates, physical bandpass filters, or polarization controlling devices except for one polarized beam splitter and a polarization-independent isolator. In the experiment, self-started stable mode locking pulse trains are obtained with four different cavity lengths: 110 m, 66 m, 50 m, and 26 m. To make clear the mechanism of pulse formation of this kind of simplified fiber laser, the characteristics of which are called an artificial saturable absorber, are discussed and the influences of these parameters on mode locking are also analyzed.
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We demonstrated an all-normal-dispersion Yb-doped mode-locked fiber laser based on Bi2Se3 topological insulator (TI). Different from previous TI-mode-locked fiber lasers in which TIs were mixed with film-forming agent, we used a special way to paste a well-proportioned pure TI on a fiber end-facet. In this way, the effect of the film-forming agent could be removed, thus the heat deposition was relieved and damage threshold could be improved. The modulation depth of the Bi2Se3 film was measured to be 5.2%. When we used the Bi2Se3 film in the Yb-doped fiber laser, the mode locked pulses with pulse energy of 0.756 nJ, pulse width of 46 ps and the repetition rate of 44.6 MHz were obtained. The maximum average output power was 33.7 mW. When the pump power exceeded 270 mW, the laser can operate in multiple pulse state that six-pulse regime can be realized. This contribution indicates that Bi2Se3 has an attractive optoelectronic property at 1µm waveband.
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We report a core-pumped all-normal dispersion mode-locked Nd-doped fiber laser at 910 and 935 nm. The pulse is compressed to 198 fs, and the pulse energy is 1.3 nJ. The slope efficiency is more than 14%. This laser is tested as the optical source for the two-photon fluorescence imaging of pollen.
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Tecnología de Fibra Óptica/instrumentación , Láseres de Estado Sólido , Transferencia de Energía , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
We demonstrated a high-repetition-rate Q-switched fiber laser with topological insulator Bi2Se3 absorber. The absorber was made into a film structure by spin-coating method using few-layer Bi2Se3 nano-platelets which had regular shape. The uniform film had a low saturable optical intensity of 11 MW/cm(2), which is the lowest saturable optical intensity in the saturable absorbers made by topological insulator till now. By inserting the absorber film into an Erbium-doped fiber laser, a high-repetition Q-switched laser with the repetition rates from 459 kHz to 940 kHz was achieved. The maximum output power was 22.35 mW with the shortest pulse duration of 1.9 µs. To the best of our knowledge, both of the repetition rate and the output power were the highest values among the Q-switched fiber lasers with topological insulator absorber.
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We designed a new kind of mode-locked fiber laser based on fiber arrays, where the central core is doped. A theoretical model is given for an all-fiber self-starting mode-locked laser based on this kind of doped fiber array. Two different kinds of fiber lasers with negative dispersion and positive dispersion are simulated and discussed. The stable mode-locked pulses are generated from initial noise conditions by the realistic parameters. The process of self-starting mode-locking multipulse transition and the relationship between the energy of the central core and the propagation distance of the pulses are discussed. Finally, we analyze the difference between the averaged mode-locked laser and the discrete mode-locked laser.