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BACKGROUND: One-third of diffuse large B-cell lymphoma (DLBCL) patients suffer relapse after standard treatment. Eukaryotic initiation factor 3a (eIF3a) is a key player in the initial stage of translation, which has been widely reported to be correlated with tumorigenesis and therapeutic response. This study aimed to explore the biological role of eIF3a, evaluate its prognostic and therapeutic potential in DLBCL. METHODS: RNA-seq datasets from GEO database were utilized to detect the expression and prognostic role of eIF3a in DLBCL patients. Protein level of eIF3a was estimated by western blot and immunohistochemical. Next, DLBCL cells were transfected with lentiviral vector either eIF3a-knockdown or empty to assess the biological role of eIF3a. Then, samples were divided into 2 clusters based on eIF3a expression and differentially expressed genes (DEGs) were identified. Function enrichment and mutation analysis of DEGs were employed to detect potential biological roles. Moreover, we also applied pan-cancer and chemosensitivity analysis for deep exploration. RESULTS: eIF3a expression was found to be higher in DLBCL than healthy controls, which was associated with worse prognosis. The expression of eIF3a protein was significantly increased in DLBCL cell lines compared with peripheral blood mononuclear cells (PBMCs) from healthy donors. eIF3a knockdown inhibited the proliferation of DLBCL cells and the expression of proliferation-related proteins and increase cell apoptosis rate. Besides, 114 DEGs were identified which had a close linkage to cell cycle and tumor immune. eIF3a and DEGs mutations were found to be correlated to chemosensitivity and vital signal pathways. Pan-cancer analysis demonstrated that high eIF3a expression was associated with worse prognosis in several tumors. Moreover, eIF3a expression was found to be related to chemosensitivity of several anti-tumor drugs in DLBCL, including Vincristine and Wee1 inhibitor. CONCLUSIONS: We firstly revealed the high expression and prognostic role of eIF3a in DLBCL, and eIF3a might promote the development of DLBCL through regulating cell proliferation and apoptosis. eIF3a expression was related to immune profile and chemosensitivity in DLBCL. These results suggest that eIF3a could serve as a potential prognostic biomarker and therapeutic target in DLBCL.
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Antineoplásicos , Linfoma Difuso de Grandes Células B , Humanos , Leucócitos Mononucleares , Proliferação de Células/genética , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Fatores de Iniciação de Peptídeos/farmacologia , Fatores de Iniciação de Peptídeos/uso terapêutico , Linhagem Celular TumoralRESUMO
Targeted protein degradation technology has gained substantial momentum over the past two decades as a revolutionary strategy for eliminating pathogenic proteins that are otherwise refractory to treatment. Among the various approaches developed to harness the body's innate protein homeostasis mechanisms for this purpose, lysosome targeting chimeras (LYTACs) that exploit the lysosomal degradation pathway by coupling the target proteins with lysosome-trafficking receptors represent the latest innovation. These chimeras are uniquely tailored to degrade proteins that are membrane-bound and extracellular, encompassing approximately 40% of all proteome. Several novel LYTAC formulas have been developed recently, providing valuable insights for the design and development of therapeutic degraders. This review delineates the recent progresses of LYTAC technology, its practical applications, and the factors that dictate target degradation efficiency. The potential and emerging trends of this technology are discussed as well. LYTAC technology offers a promising avenue for targeted protein degradation, potentially revolutionizing the therapeutic landscape for numerous diseases.
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Fast development of space technologies poses a strong challenge for elastic materials, which need to be not only lightweight, strong and compliant, but also able to maintain stable elasticity over a wide temperature range1-4. Here we report a lightweight magnesium-scandium strain glass alloy (Mg with 21.3 at.% Sc) that meets this challenge. This alloy is as light (density ~2 g cm-3) and compliant as organic-based materials5-7 like bones and glass fibre reinforced plastics, but in contrast with those materials, it possesses a nearly temperature-independent (or Elinvar-type), ultralow Young's modulus (~20-23 GPa) over a wide temperature range from room temperature down to 123 K; a higher yield strength of ~200-270 MPa; and a long fatigue life of over one million cycles. As a result, it exhibits a relatively high, temperature-independent elastic energy density of ~0.5 kJ kg-1 among known materials at a moderate stress level of 200 MPa. We show that its exceptional properties stem from a strain glass transition, and the Elinvar-type elasticity originates from its moderate elastic softening effect cancelling out the ever-present elastic hardening. Our findings provide insight into designing materials that possess unconventional and technologically important elastic properties.
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Ligas , Módulo de Elasticidade , Elasticidade , Teste de Materiais , TemperaturaRESUMO
In this manuscript, a narrow linewidth fiber amplifier based on confined-doped fiber is established, and the power scaling and beam quality maintaining capabilities of this amplifier are investigated. Benefitted from the large mode area of the confined-doped fiber and precisely controlling the Yb-doped region in the fiber core, the stimulated Brillouin scattering (SBS) and transverse mode instability (TMI) effects are effectively balanced. As a result, a 1007 W signal laser with just 1.28â GHz linewidth is obtained by combining the advantages of confined-doped fiber, near-rectangular spectral injection, and 915â nm pump manner. As far as we know, this result is the first beyond kilowatt-level demonstration of all-fiber lasers with GHz-level linewidth, which could provide a well reference for simultaneously controlling spectral linewidth, suppressing the SBS and TMI effects in high-power, narrow-linewidth fiber lasers.
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Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus Chaetomium nigricolor F5 guided the isolation of five novel cytochalasans, chamisides B-F (1-5), and two known ones, chaetoconvosins C and D (6 and 7). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds 1-3 share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system. Remarkably, compound 5 with a relatively flexible side chain showed promising inhibition activity against the cholesterol transporter protein Niemann-Pick C1-like 1 (NPC1L1), expanding the function of cytochalasans.
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Sordariales , Estrutura Molecular , Fungos , Citocalasinas/farmacologia , Citocalasinas/químicaRESUMO
Pinholes in A l/M g F 2 were first inferred by the transmittance enhancement in Larruquert group's research. However, no direct proof was reported to verify the existence of the pinholes in A l/M g F 2. In the past 80 years, pinholes were first observed by dark-field microscopy and bright-field microscopy in the transmission mode. They were small and on the order of several hundred nanometers to several micrometers. Essentially, the pinhole was not a real hole, partially because of the lack of the Al element. Increasing the thickness of Al cannot reduce the size of the pinholes. The occurrence of the pinholes was dependent on the deposition rate of the Al film and the substrate heating temperature, and it was independent of the substrate materials. This research eliminates an otherwise easily ignored scattering source, and it will benefit the development of ultra-precise optics, including mirrors for gyro-lasers, the detection of gravitational waves, and coronagraph detection.
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The emission lines of 140-180 nm are auroral bands of N 2 Lyman-Birge-Hopfield, and they have been imaging targets of many satellites that need reflective mirrors. To obtain good imaging quality, the mirrors also should have excellent out-of-band reflection suppression as well as high reflectance at working wavelengths. We designed and fabricated non-periodic multilayer L a F 3/M g F 2 mirrors with working wave bands of 140-160 nm and 160-180 nm, respectively. We used a match design method and deep search method to design the multilayer. Our work has been utilized in the new wide-field auroral imager of China, and the application of these notch mirrors with excellent out-of-band suppression reduces the utilization of corresponding transmissive filters in the optical system of space payload. Furthermore, our work provides new routes for the design of other reflective mirrors in the far ultraviolet region.
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A superfluorescent fiber source (SFS) is a special fiber source that commonly possesses high temporal stability and a wide spectral linewidth. In this work, an all-fiberized linearly polarized SFS with, to our knowledge, record output power and near-diffraction-limited beam quality is presented. Up to 5.03 kW SFS is achieved at a pump power of 6.18 kW with a corresponding conversion efficiency of â¼81.1%. At maximum output power, the signal-to-noise ratio to background spectral noise is over 50 dB, the polarization extinction ratio is â¼17d B, and the beam quality factor is M x 2=1.49, M y 2=1.44. Further comparisons confirm the power scalability of fiber amplifiers employing SFSs as seed lasers. Overall, this work could provide a good reference for potential exploration of high-power fiber laser systems.
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In this work, we conduct a detailed experimental study on the impact of signal bandwidth on the TMI threshold of fiber amplifiers. Both the filtered superfluorescent fiber sources and the phase-modulated single-frequency lasers are employed to construct seed lasers with different 3 dB spectral linewidths ranging from 0.19 nm to 7.97 nm. The TMI threshold of the fiber amplifier employing those seed lasers are estimated through the intensity evolution of the signal laser, and different criteria have been utilized to characterize the spectral linewidth of the seed lasers. Notably, the experimental results reveal that the TMI threshold of fiber amplifiers grows, keeps constant, and further grows as a function of spectral linewidth of seed lasers. Our experimental results could provide a well reference to understand the mechanism of the TMI effect and optimize the TMI effect in high-power fiber amplifiers.
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In this work, a bidirectional tandem-pumped high-power narrow-linewidth confined-doped ytterbium fiber amplifier is demonstrated based on side-coupled combiners. Benefiting from the large-mode-area design of the confined-doped fiber, the nonlinear effects, including stimulated Raman (SRS) and stimulated Brillouin scattering (SBS), are effectively suppressed. While the transverse mode instability (TMI) effect is also mitigated through the combination of confined-doped fiber design and the bidirectional tandem pumping scheme. As a result, narrow-linewidth fiber laser with 5.96 kW output power is obtained, the slope efficiency and the 3-dB linewidth of which are â¼81.7% and 0.42 nm, respectively. The beam quality is well maintained during the power scaling process, being around M2 = 1.6 before the TMI occurs, and is well kept (M2 = 2.0 at 5.96 kW) even after the onset of TMI. No SRS or SBS is observed at the maximum output power, and the signal-to-noise ratio reaches as high as â¼61.4 dB. To the best of our knowledge, this is the record power ever reported in narrow-linewidth fiber lasers. This work could provide a good reference for realizing high-power high-brightness narrow-linewidth fiber lasers.
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In this paper, we investigate the performances of an in-house fabricated confined-doped active fiber in the applications of all-fiber high-power single-frequency amplifiers. A 210-W single-frequency single-mode fiber laser is obtained directly, which confirms the excellent performance of the confined-doped active fiber for high-power single-mode operation. To further demonstrate the power scalability of the fiber amplifier, the strategy of applying a temperature gradient along the active fiber is investigated numerically and experimentally, and an up to â¼75% enhancement of the stimulated Brillouin scattering (SBS) threshold is achieved. As a result, a 368-W single-frequency fiber laser is obtained with the beam quality factor of Mx2 = 1.19, My2 = 1.26. Overall, the technique of the confined-doped active fiber provides a promising approach to scale the output power of single-frequency single-mode fiber lasers.
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A novel CaIn2S4with three-dimensional octahedral nano-blocks (ONBs) are successfully synthesized on fluorine-doped tin oxide (FTO) substrate by a simple hydrothermal method. The CaIn2S4ONBs are uniform grown and scattered on the whole FTO substrate with high regular and symmetric morphology as well as average diagonal length of about 600 nm. Based on the as-synthesized CaIn2S4ONBs, a photodetector (PD) is fabricated. Satisfyingly, it is found that the CaIn2S4ONBs PD achieves a broad-band response ranging from ultraviolet (UV) to visible ( vis) light at zero bias voltage. It is also significant that the CaIn2S4ONBs PD enables a fast response, in which the rise time and decay time are less than 0.15 and 0.2 s, respectively. Furthermore, the morphological evolution of the CaIn2S4ONBs and plausible UV/vis detection mechanism of the CaIn2S4ONBs PD are discussed.
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BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection rates have been changing with different populations and geographic areas. We systematically evaluated the longitudinal trends in H. pylori prevalence in China over the past decades. METHODS: We performed a systematic review of literature reporting the prevalence of H. pylori infection in mainland China from 1990 to 2019 in the PubMed and China National Knowledge Infrastructure databases. We conducted a meta-analysis of qualified studies using a random effects model to estimate the pooled prevalence with a 95% confidence interval (95%CI). RESULTS: A total of 412 eligible studies with 1 377 349 subjects were included. The pooled H. pylori prevalence was 44.2% (95%CI: 43.0-45.5%) in mainland China, with an estimated 589 million individuals infected with H. pylori. The prevalence was relatively high in the Northwest (51.8%, 95%CI: 47.5-56.1%), East (47.7%, 95%CI: 45.4-50.0%), and Southwest China (46.6%, 95%CI: 42.1-51.1%). The prevalence significantly decreased from 58.3% (95%CI: 50.7-65.5%) in the period 1983-1994 to 40.0% (95%CI: 38.2-41.8%) in the period 2015-2019. The prevalence increased with age, ranging from 28.0% (95%CI: 23.9-32.5%) in children and adolescents to 46.1% (95%CI: 44.5-47.6%) in adults. CONCLUSION: Although the burden of H. pylori infections is still huge in China, the infection rate has been decreasing over the past decades. Targeted H. pylori eradication strategies may be considered in areas or populations with a high incidence of gastric cancer.
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Infecções por Helicobacter , Helicobacter pylori , China/epidemiologia , Infecções por Helicobacter/epidemiologia , Humanos , PrevalênciaRESUMO
In this paper, we demonstrate a high-power linearly polarized all-fiberized superfluorescent fiber source (SFS) with near-diffraction-limited beam quality. The laser system is based on a master oscillator power amplifier configuration, which mainly consists of a polarization-maintained (PM) broadband SFS and multistage PM fiber amplifiers. A linearly polarized fiber laser over 3 kW is obtained at a pump power of about 4.3 kW with the corresponding slope efficiency of 71.9%. The polarization extinction ratio and the beam quality (M2 factor) of the output laser are about 12.7 dB and 1.18, respectively, at the maximum output power. To the best of our knowledge, this is the highest output power of a linearly polarized broadband SFS with near-diffraction-limited beam quality.
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The color stability of anthocyanins (ACN) has been shown to be improved by interaction with whey proteins (WP). In this study, we explore the ACN-WP interaction using Fourier transform infrared spectroscopy (IR). ACN from purple corn, grape, and black carrot (50 µM) were evaluated. IR spectra (4000-700 cm-1) were collected for native and preheated (40-80 °C) WP (5 mg/mL) and ACN-WP mixtures at pH 7.4. Soft independent modeling of class analogy was used to analyze the IR data. The WP secondary structure changed after heat treatments and after interaction with ACN. As expected, the WP α-helices decreased, and ß-sheet increased after heat treatment. The intensities of the WP amide I and II bands decreased after ACN addition, revealing a decrease in the WP α-helix content. Higher preheating temperatures (70-80 °C) resulted in a more disordered WP structure that favored stronger WP-ACN interactions related to amide III changes. Addition of ACN stabilized WP structure due to heat denaturation, but different ACN structures had different binding affinities with WP. WP structure had less change after interaction with ACN with simpler structures. These results increase our understanding of ACN-WP interactions, providing a potential strategy to extend anthocyanin color stability by WP addition.
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Antocianinas , Vitis , Antocianinas/química , Temperatura Alta , Espectroscopia de Infravermelho com Transformada de Fourier , Proteínas do Soro do Leite/químicaRESUMO
In this paper, we demonstrate experimental investigations on kilowatt-level Yb-Raman fiber amplifiers (YRFAs) employing a superfluorescent fiber source (SFS) or a multi-longitudinal mode fiber oscillator (OSC) as the Raman-pump laser. Through comparing the output properties of the two YRFAs, the experimental results reveal that the YRFA employing the SFS is superior to the YRFA employing the OSC in the performances of power scalability and narrow-linewidth operation. Meanwhile, about 1.16 kW Raman-signal laser at 1120 nm is obtained through the YRFA employing the SFS as the Raman-pump laser. Overall, the presentation could provide an effective solution for the design of high-power narrow linewidth YRFAs.
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In this Letter, we report a high-power narrow-linewidth Yb-Raman fiber amplifier with a high second-order Raman threshold and high intensity stability. By employing two temporally stable seed lasers, over 2 kW output power at 1120 nm is achieved at a pump power of 2.6 kW with an optical-to-optical efficiency of 76.3%. The 3 dB linewidth of the 1120 nm Raman-signal laser varies slightly from 0.41 nm to 0.53 nm, and the power ratio of the second-order Raman Stokes light is only about ${-}{46.3}\;{\rm{dB}}$ at the output power of 2 kW. The results further confirm that the technique of employing temporally stable seed lasers is superior to the power scaling of narrow-linewidth Yb-Raman fiber amplifiers. To the best of our knowledge, it is the first demonstration of an over 2 kW narrow-linewidth fiber laser operating at 1120 nm.
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In this Letter, we propose a scheme to use a temporally stable pump source in a high-power random distributed feedback Raman fiber laser (RRFL) with a half-open cavity. Different from conventional pump manners, the pump source is based on an Yb-doped fiber amplifier, seeded by a temporally stable phase-modulated single-frequency fiber laser for suppressing the spectral broadening and second-order Raman Stokes generation in the output laser. Using a piece of 50-m-long 20/400 µm passive fiber, the maximum output power of 1570 W was obtained with a pump power of 2025 W. The conversion efficiency with respect to the pump power was 77.5%. To the best of our knowledge, this is the highest output power ever reported in a RRFL to date. This work could provide a novel method for power scaling of RRFLs.
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BACKGROUND: Mature T-cell lymphomas (MTCLs), a group of diseases with high aggressiveness and vulnerable prognosis, lack for the accurate prognostic stratification systems at present. Novel prognostic markers and models are urgently demanded. Aberrant lipid metabolism is closely related to the tumor progression but its prognostic significance in MTCLs remains unexplored. This study aims to investigate the relationship between dysregulated lipid metabolism and survival prognosis of MTCLs and establish a novel and well-performed prognostic scoring system for MTCL patients. METHODS: A total of 173 treatment-naive patients were enrolled in this study. Univariate and multivariate Cox regression analysis were performed to assess the prognostic significance of serum lipid profiles and screen out independent prognostic factors, which constituted a novel prognostic model for MTCLs. The performance of the novel model was assessed in the training and validation cohort, respectively, by examining its calibration, discrimination and clinical utility. RESULTS: Among the 173 included patients, 115 patients (01/2006-12/2016) constituted the training cohort and 58 patients (01/2017-06/2020) formed the validation cohort. Univariate analysis revealed declined total cholesterol (TC, P = 0.000), high-density lipoprotein cholesterol (HDL-C, P = 0.000) and increased triglycerides (TG, P = 0.000) correlated to inferior survival outcomes. Multivariate analysis revealed extranodal involved sites ≥ 2 (hazard ratio [HR]: 2.439; P = 0.036), ß2-MG ≥ 3 mg/L (HR: 4.165; P = 0.003) and TC < 3.58 mmol/L (HR: 3.338; P = 0.000) were independent predictors. Subsequently, a novel prognostic model, EnBC score, was constructed with these three factors. Harrell's C-index of the model in the training and validation cohort was 0.840 (95% CI 0.810-0.870) and 0.882 (95% CI 0.822-0.942), respectively, with well-fitted calibration curves. The model divided patients into four risk groups with distinct OS [median OS: not available (NA) vs. NA vs. 14.0 vs. 4.0 months, P < 0.0001] and PFS (median PFS: 84.0 vs. 19.0 vs. 8.0 vs. 1.5 months, P < 0.0001). Time-dependent receiver operating characteristic curve and decision curve analysis further revealed that EnBC score provided higher diagnostic capacity and clinical benefit, compared with International Prognostic Index (IPI). CONCLUSION: Firstly, abnormal serum lipid metabolism was demonstrated significantly related to the survival of MTCL patients. Furthermore, a lipid-covered prognostic scoring system was established and performed well in stratifying patients with MTCLs.
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BACKGROUND: Diagnostic type II endometrial carcinoma (EC) is considered more aggressive and has a poorer prognosis than type I EC; differentiation between them is helpful for preoperative clinical decision-making. However, the diagnostic value of the apparent diffusion coefficient (ADC) in differentiating them remains unclear. PURPOSE: To investigate the value of ADC in differentiating type II EC from type I EC. MATERIAL AND METHODS: Ninety-four patients with EC who underwent diffusion-weighted imaging (DWI) were retrospectively included and divided into type I and type II subgroups, based on the postoperative pathologic results. We analyzed the clinical characteristics, conventional magnetic resonance imaging manifestations, and ADC mean values (ADCmean), ADC minimum values (ADCmin), and ADC max values (ADCmax). Receiver operating characteristic (ROC) curve analysis was further used to assess the predictive performance. RESULTS: The ADCmean, ADCmin, and tumor size differed significantly between the two subtypes. The area under the ROC curve (AUC) for ADCmean and ADCmin was 0.787 (95% confidence interval [CI] = 0.692-0.88) and 0.835 (95% CI = 0.751-0.919) for predicting type II EC, respectively. The optimal cut-off value of ADCmean for prediction was 0.757 × 10-3 mm2/s with a sensitivity of 91%, a specificity of 58%, and an accuracy of 74%, while for ADCmin was 0.637 × 10-3 mm2/s with a sensitivity of 82%, a specificity of 73%, and an accuracy of 75%. CONCLUSION: EC with lower ADCmean and ADCmin values derived from DWI, and a larger size, are indicative of type II EC.