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Efficient diode-pumped continuous-wave (CW) and wavelength tunable Tm:YAP lasers based on the vibronic and electronic transitions are investigated. A total maximum output power of 4.1 W is achieved with multi-wavelength output around 2162 nm and 2274 nm, corresponding to a slope efficiency of 29.8% for a 3 at. % Tm:YAP crystal. A maximum output power of 2.48 W with a slope efficiency of 25.4% is obtained at 2146 nm for a 4 at. % Tm:YAP crystal. Using a birefringent filter (BF), the emission wavelengths of the Tm:YAP laser are tuned over spectral ranges of 59 nm from 2115 nm to 2174 nm and 127 nm from 2267 nm to 2394 nm, respectively, which is the first demonstration of wavelength tunable Tm:YAP laser based on the electronic transition 3H4â3H5 and vibronic transition 3F4â3H6, to the best of our knowledge. The results show great potentials of the Tm:YAP crystal for realizing efficient lasers in the spectral range of 2.1-2.4 µm.
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Yb-doped sesquioxides represent one of the most excellent laser crystals applying for high-power ultrafast lasers owing to their very high thermal conductivities and broadband emission spectra. Pumped by a high-brightness Yb-fiber laser at 976â nm, the Yb:Lu2O3 laser delivers a maximum output power that amounts to 3.55â W in the continuous-wave regime with an optical efficiency of 75%. In the mode-locked regime, 90-fs pulses were generated via soft-aperture Kerr-lens mode-locking at 1080.6â nm with an average output power of 2.85â W, which corresponds to an optical efficiency of 60.3% and a slope efficiency of 68.8%. Average output power of the mode-locked Yb:Lu2O3 laser can be further scaled to 3.05â W at the expense of the pulse duration (178â fs), which corresponds to an optical efficiency as high as 64.5%. To the best of our knowledge, it is the highest optical efficiency ever reported from any solid-state Kerr-lens mode-locked Yb lasers.
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RESEARCH QUESTION: Is the novel homozygous nonsense variant of AK7 associated with multiple morphological abnormalities of the sperm flagella (MMAF), a specific type of oligoasthenoteratozoospermia leading to male infertility? DESIGN: Whole-exome sequencing and Sanger sequencing were performed to identify potential gene variants. Immunoblotting and immunofluorescence were applied to confirm the relationship between mutated genes and disease phenotypes. The concentration of reactive oxygen species and the rate of apoptosis were measured to evaluate the mitochondrial function of spermatozoa. Transmission electron microscopy and scanning electron microscopy were employed to observe sperm ultrastructure. RESULTS: A novel homozygous nonsense variant of AK7, c.1153A>T (p. Lys385*), was identified in two infertile siblings with asthenoteratozoospermia through whole-exome sequencing. Both immunoblotting and immunofluorescence assays showed practically complete absence of AK7 in the patient's spermatozoa. Additionally, the individual with the novel AK7 variant exhibited a phenotype characterized by severe oxidative stress and apoptosis caused by mitochondrial metabolic dysfunction of spermatozoa. Notably, remarkable flagellar defects with multiple axonemes in uniflagellate spermatozoa, accompanied by mitochondrial vacuolization, were observed; this has not been reported previously in patients with other AK7 variants. CONCLUSIONS: This study found that a novel identified homozygous nonsense variant of AK7 may be associated with MMAF-related asthenoteratozoospermia. The observed functional associations between mitochondria and sperm flagellar assembly provide evidence for potential mutual regulation between AK7 and flagella-associated proteins during spermatogenesis.
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Adenilato Quinasa , Astenozoospermia , Cola del Espermatozoide , Adulto , Humanos , Masculino , Astenozoospermia/genética , Astenozoospermia/patología , Codón sin Sentido , Secuenciación del Exoma , Homocigoto , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Mitocondrias/ultraestructura , Mitocondrias/genética , Mitocondrias/patología , Linaje , Cola del Espermatozoide/patología , Cola del Espermatozoide/ultraestructura , Espermatozoides/ultraestructura , Espermatozoides/anomalías , Adenilato Quinasa/genéticaRESUMEN
This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.
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Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Relación Estructura-Actividad , Animales , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Benzodioxoles/farmacología , Benzodioxoles/síntesis química , Benzodioxoles/química , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Células HeLa , Movimiento Celular/efectos de los fármacos , Embrión de PolloRESUMEN
Yb-doped fluoride has been demonstrated to be potential crystals for application in efficient ultrafast lasers. However, the trade-off between the shorter pulses with higher efficiencies is a challenge. In this work, using Y b,G d:C a S r F 2 crystal, we report on a sub-50-fs Kerr-lens mode-locked oscillator with an optical efficiency up to 44%. Pumped by a 976-nm diffraction-limited fiber laser and using chirped mirrors combined with prism pairs for the dispersion compensation, a pulse as short as 46 fs was obtained with 620-mW output power, corresponding to an optical efficiency more than 40%. Stable Kerr-lens mode-locking with RMS of output power lower than 0.3% and beam quality factors M 2<1.14 were achieved. Moreover, a maximum output power of 780 mW was obtained in continuous-wave operation with 55.3% optical efficiency. To the best of our knowledge, the results in this work represent the shortest pulses generated from Yb-doped fluoride lasers as well as the highest optical efficiencies ever reported in sub-100 fs Yb bulk lasers.
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In this paper, a high-power all-solid-state ultrafast 2 µm mode-locked laser is investigated. The particularity of this laser is the simultaneous utilization of two Tm:YAP crystals in the same resonant cavity, independently pumped by two laser diodes. Using a 20% output coupler, pulses with output power as high as 1.83 W are achieved at a wavelength of 1938 nm with a pulse duration of 1.97 ps and a pulse repetition frequency of 100 MHz. To our knowledge, this mode-locked laser achieves the highest output power of any mode-locked Tm:YAP ultrafast laser reported to date. In addition, this paper provides a new approach to solve the problem of low output power due to multi-mode low-brightness laser diode pumping.
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A high-efficiency, high-energy, narrow bandwidth, hundred-nanosecond pulse width 355â nm ultraviolet (UV) laser was realized. A high-energy single-frequency 1064â nm fundamental laser was demonstrated firstly with multistage end-pumped preamplifiers and side-pumped main amplifiers. The corresponding pulse energy, repetition rate, pulse duration, bandwidth, and beam quality factor M2 were determined to be 221â mJ, 100â Hz, 156â ns, 2.25â MHz, and 1.23, respectively. By using type-I phase-matching LBO crystal for second harmonic generation (SHG) and type-II phase-matching LBO crystal for the sum frequency generation of the third harmonic, 67â mJ, a narrow bandwidth 355â nm UV laser was obtained with a pulse width of 137â ns and an energy stability of RMS < 1.2%@2â h. The fundamental to UV optical conversion efficiency was 30.3%. Our results provided a new way for generating high-energy, narrow bandwidth hundred-nanosecond 355â nm UV lasers used for direct-detection Doppler wind lidar (DWL) system.
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A diode-pumped self-Q-switched 2.74 µm Er:Lu2O3 crystal solid-state laser has been experimentally and theoretically studied. Without any additional modulation elements, stable self-Q-switched pulses with a pulse width of 145.3 ns, a repetition rate of 227.8 kHz, and an average output power of 877 mW were generated. Considering the excited-state absorption on the laser photons of the Er:Lu2O3 crystal, we have simulated the dynamic process of self-pulsed generation by solving the rate equations numerically. The simulation results are consistent with the typical characteristics of a Q-switched laser.
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BACKGROUND: Premacular hemorrhage is among the causes of sudden deterioration of visual acuity. This study aimed to investigate the therapeutic outcomes of a new Q-switched Nd:YAG laser on premacular hemorrhage. METHODS: Retrospective, case series study of 16 eyes from 16 patients diagnosed with premacular hemorrhage, including 3 cases of Valsalva retinopathy, 8 cases of retinal macroaneurysm, 3 cases of diabetic retinopathy, 1 case of trauma-related hemorrhage and 1 case with leukemia. A 1064nm Q-switched Nd:YAG laser was performed to puncture the posterior hyaloid and inner limiting membrane to drain the hemorrhage. RESULTS: The success rate of 16 patients with premacular hemorrhage drainage was 100% in this study. Improved visual acuity was observed in each patient. CONCLUSIONS: In this case series of 16 patients, the new Q-switched Nd:YAG laser was successful in draining premacular hemorrhage with no serious complications.
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Terapia por Láser , Láseres de Estado Sólido , Humanos , Resultado del Tratamiento , Láseres de Estado Sólido/uso terapéutico , Estudios Retrospectivos , Terapia por Láser/efectos adversos , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/etiología , Hemorragia Retiniana/cirugía , Cuerpo VítreoRESUMEN
A modified Frantz-Nodvik (F-N) equation and a simple one-dimensional unfolded slicing model for numerically simulating high-power Innoslab picosecond amplifier are developed for the first time. The anisotropic stimulated emission cross-section of laser crystal, the influence of the tilted optical path, the spatial overlap of the seed and pump laser, as well as the pump absorption saturation effect are considered. Based on the as-developed model, 4-, 6- and 8-pass schemes high-power Nd:YVO4 Innoslab picosecond amplifiers are designed with output powers of 76.2 W, 81.4 W, and 85.5 W, respectively. The experimental results agree well with that of numerical simulation, indicating that our model is a powerful tool and paves a new way for designing and optimizing high-power Innoslab picosecond laser amplifier.
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In this paper, Ti3C2Tx MXene prepared by LiF/HCl etching method was spin-coated on glass substrate and sapphire substrate as the saturable absorber (SA), and the MXene SA is combined with Yb: LuAG single crystal fiber (SCF) for the first time to achieve a 1.05 µm passively Q-switched pulsed laser output with the average power, pulse width, and repetition frequency of 1.989 W, 149.6 ns, and 365.44 kHz, respectively, which is the highest average power ever reported for passively Q-switched SCF pulsed lasers. This work enriches the research on SCF pulsed lasers and provides a feasible approach for achieving high-power all-solid-state pulsed lasers.
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We demonstrate the direct generation of visible vortex beams (LG01 mode) from a doughnut-shaped diode-pumped Pr:YLF laser. In continuous-wave mode, the maximum vortex output power was 36 mW at 523 nm, 354 mW at 607 nm, 838 mW at 639 nm, 722 mW at 721 nm, respectively. Moreover, based on this operation, the orange and red passively Q-switched vortex lasers were also achieved by inserting a Co:MgAl2O4 crystal into the laser cavity as a saturable absorber. The shortest pulse width of Q-switched vortex laser was 58 ns for 607 nm, and 34 ns for 639 nm, respectively. Our work provides a reliable and efficient method for the direct generation of visible vortex lasers for potential applications.
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Cascade transitions of Ho3+:5I6â5I7 and 5I7â5I8 provide a platform for a dual-wavelength mid-infrared (MIR) laser. In this paper, a continuous wave cascade MIR Ho:YLF laser operating at 2.1 and 2.9â µm is realized at room temperature. The total output power of 929â mW with 778â mW at 2.9â µm and 151â mW at 2.1â µm is obtained under the absorbed pump power of 5 W. Compared to the non-cascade mode, 2.9-µm lasing threshold is reduced by 10.3% and the slope efficiency is increased by 76.1% with the supports of cascade lasing at 2.1â µm. However, 2.9-µm lasing is the key population accumulation of the 5I7 level, which thus efficiently reduces the threshold and improves the output power of the 2.1-µm laser. Our results put forward a way for generating cascade dual-wavelength MIR lasing in Ho3+-doped crystals.
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BACKGROUND: To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment. METHODS: Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed. RESULTS: A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001-1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890-220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915-0.990, P = 0.014). CONCLUSION: Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.
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Coriorretinopatía Serosa Central , Biomarcadores , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/cirugía , Coroides , Angiografía con Fluoresceína , Humanos , Rayos Láser , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
Pulses as short as 17.8 fs with a spectral bandwidth of 145 nm and central wavelength of 1118 nm have been generated from a Kerr-lens mode-locked Yb:CALGO oscillator. The oscillator operating at an average power of 26 mW and a repetition rate of 95.9 MHz is pumped by a cost-effective single-mode fiber coupled laser diode emitting 800 mW at 976 nm. The dispersion is compensated using a prism pair combined with broadband chirp mirrors. To the best of our knowledge, the pulse durations corresponding to approximately 4.8 optical cycle pulses are the shortest achieved durations through a Yb-doped bulk oscillator.
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BACKGROUND: Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. METHODS: Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. RESULTS: Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. CONCLUSIONS: This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.
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Células Intersticiales del Testículo/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal/genética , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Silenciador del Gen , Humanos , Interleucina-6/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Masculino , MicroARNs/genética , Fosfohidrolasa PTEN/genética , ARN Largo no Codificante/genética , Transducción de Señal/efectos de los fármacos , Testosterona/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Nanoscale mapping of electric polarizability in a heterogeneous dielectric material with surface irregularities is of scientific and technical significance, but remains challenging. Here, we present an approach based on intermodulation electrostatic force microscopy (EFM) in conjunction with finite element computation for precise and high-resolution mapping of polarizability in dielectric materials. Instead of using electrostatic force in conventional quantitative EFM approaches, the force gradient is acquired to achieve an unprecedented spatial resolution. In the meantime, the finite element model is applied to eliminate the interference from the heterogeneity and surface irregularity of the sample. This approach directly reveals the high polarization ability of the amorphous region in a ferroelectric, semi-crystalline polymer with significant surface roughness, i.e. poly (vinylidene fluoride-co-chlorotrifluoroethylene), in which the result is consistent with the predicted data in the latest research. This work presenting a quantitative approach to nanoscale mapping of electric polarizability with unprecedented spatial resolution may help to reveal the complex property-structure correlation in heterogeneous dielectric materials.
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In this work, a novel, to the best of our knowledge, α-BaTeMo2O9 crystal-based acousto-optical modulator is designed and successfully applied in actively Q-switched and mode-locked Er-doped fiber lasers (EDFLs) and Yb-doped fiber lasers (YDFLs) operating at 1.5 and 1.0 µm. The shortest pulse width of 429 ns and 1.37 µs are obtained in actively Q-switched EDFLs and YDFLs, respectively. For actively mode-locked operation, a pulse width of 11.32 ns at a modulation frequency of 3.19 MHz is obtained in EDFLs, while it is 29.9 ns at 1.036 MHz in YDFLs. The results indicate that the α-BaTeMo2O9 crystal is a promising candidate for all-fiber active modulators.
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A high-gain two-stage double-pass off-axis Nd:YVO4 picosecond laser amplifier has been developed. The comprehensive influence of crystal doping concentration and pump beam quality on the small-signal gain of the Nd:YVO4 amplifier is theoretically analyzed with a model developed by considering energy transfer upconversion and pump light absorption saturation effect. The thermal effect of Nd:YVO4 crystal with different doping concentrations, undoped end cap lengths, and pump beam quality is investigated as well. Based on the theoretical analysis, a high-gain two-stage and double-pass off-axis Nd:YVO4 amplifier based on picosecond fiber seed source is realized by choosing long-composite low-doping Nd:YVO4 crystal and with high brightness laser diode pumping, delivering a gain of 28 dB and an output pulse energy of 67.5 µJ at a repetition rate of 200 kHz.
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Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model.