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The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires effective therapies against coronavirus disease 2019 (COVID-19), and neutralizing antibodies are a promising therapy. A noncompeting pair of human neutralizing antibodies (B38 and H4) blocking SARS-CoV-2 binding to its receptor, ACE2, have been described previously. Here, we develop bsAb15, a bispecific monoclonal antibody (bsAb) based on B38 and H4. bsAb15 has greater neutralizing efficiency than these parental antibodies, results in less selective pressure and retains neutralizing ability to most SARS-CoV-2 variants of concern (with more potent neutralizing activity against the Delta variant). We also selected for escape mutants of the two parental mAbs, a mAb cocktail and bsAb15, demonstrating that bsAb15 can efficiently neutralize all single-mAb escape mutants. Furthermore, prophylactic and therapeutic application of bsAb15 reduced the viral titer in infected nonhuman primates and human ACE2 transgenic mice. Therefore, this bsAb is a feasible and effective strategy to treat and prevent severe COVID-19.
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Anticuerpos Biespecíficos/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Animales , Anticuerpos Biespecíficos/química , Anticuerpos Biespecíficos/genética , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/genética , Anticuerpos Neutralizantes/genética , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/genética , COVID-19/inmunología , COVID-19/patología , COVID-19/prevención & control , COVID-19/virología , Clonación Molecular , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Epítopos , Humanos , Macaca mulatta , Ratones , Pruebas de Neutralización , Ingeniería de Proteínas/métodos , Relación Estructura-ActividadRESUMEN
Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.
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Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.
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COVID-19 , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19 , Anticuerpos Monoclonales , Epítopos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Glicoproteína de la Espiga del CoronavirusRESUMEN
Heterojunctions combining two photocatalysts of staggered conduction and valence band energy levels can increase the photocatalytic efficiency compared to their individual components. This activity enhancement is due to the minimization of undesirable charge recombination by the occurrence of carrier migration through the heterojunction interface with separated electrons and holes on the reducing and oxidizing junction component, respectively. Metal-organic frameworks (MOFs) are currently among the most researched photocatalysts due to their tunable light absorption, facile charge separation, large surface area and porosity. The present review summarizes the current state-of-the-art in MOF-based heterojunctions, providing critical comments on the construction of these heterostructures. Besides including examples showing the better performance of MOF heterojunctions for three important photocatalytic processes, such as hydrogen evolution reaction, CO2 photoreduction and dye decolorization, the focus of this review is on describing synthetic procedures to form heterojunctions with MOFs and on discussing the experimental techniques that provide evidence for the operation of charge migration between the MOF and the other component. Special attention has been paid to the design of rational MOF heterojunctions with small particle size and controlled morphology for an appropriate interfacial contact. The final section summarizes the achievements of the field and provides our views on future developments.
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Electrical manipulation of magnetic states in two-dimensional ferromagnetic systems is crucial in information storage and low-dimensional spintronics. Spin-orbit torque presents a rapid and energy-efficient method for electrical control of the magnetization. In this letter, we demonstrate a wafer-scale spin-orbit torque switching of two-dimensional ferromagnetic states. Using molecular beam epitaxy, we fabricate two-dimensional heterostructures composed of low crystal-symmetry WTe2 and ferromagnet CrTe2 with perpendicular anisotropy. By utilizing out-of-plane spins generated from WTe2, we achieve field-free switching of the CrTe2 perpendicular magnetization. The threshold switching current density in CrTe2/WTe2 is 1.2 × 106 A/cm2, 20 times smaller than that of the CrTe2/Pt control sample even with an external magnetic field. In addition, the switching behavior can be modulated by external magnetic fields and crystal symmetry. Our findings demonstrate a controllable and all-electric manipulation of perpendicular magnetization in a two-dimensional ferromagnet, representing a significant advancement toward the practical implementation of low-dimensional spintronic devices.
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The long-term operation feature of enzymatic biofuel cell-based self-powered biosensor (EBFC-SPB) endows them with the potential to execute dual-signal biosensing without having to integrate an extra signal acquisition device. Herein, cobalt and manganese codoped CeO2 nanospheres (CoMn-CeO2 NSs) with glucose-oxidase-like and peroxidase-like activities have been developed as substrate-switched dual-channel signal transduction components in EBFC-SPB for a dual-signal assay of aflatoxin B1 (AFB1). The CoMn-CeO2 NSs modified with aptamer are anchored to a complementary DNA-attached bioanode of EBFC-SPB by base complementary pairing, which catalyze the glucose oxidation together with the glucose oxidase (GOx) on the bioanode. Once the AFB1 appears, CoMn-CeO2 NSs will be released from the bioanode due to the binding specificity of the aptamer, resulting in a decreased catalytic efficiency and the first declining stage of EBFC-SPB. Accompanied by the introduction of H2O2, the residual CoMn-CeO2 NSs on the bioanode switch to peroxidase-like activity and mediate the production of benzo-4-chlorohexadienone (4-CD) precipitate, which increases the steric hindrance and yields another declining stage of EBFC-SPB. By assessing the variation amplitudes during these two declining stages, the dual-signal assay of AFB1 has been realized with satisfying results. This work not only breaks ground in dual-signal bioassays but also deepens the application of nanozymes in EBFC-SPB.
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Aflatoxina B1 , Técnicas Biosensibles , Cerio , Técnicas Electroquímicas , Nanosferas , Aflatoxina B1/análisis , Aflatoxina B1/metabolismo , Nanosferas/química , Técnicas Biosensibles/métodos , Cerio/química , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Cobalto/química , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Manganeso/químicaRESUMEN
Exosomal miRNAs are considered promising biomarkers for cancer diagnosis, but their accuracy is severely compromised by the low content of miRNAs and the large amount of exosomal miRNAs released from normal cells. Here, we presented a dual-specific miRNA's logical recognition triggered by an entropy-driven catalysis (EDC)-enhanced system in exosomes for accurate detection of liver cancer-cell-derived exosomal miR-21 and miR-122. Taking advantage of the accurate analytical performance of the logic device, the excellent membrane penetration of gold nanoparticles, and the outstanding amplification ability of the EDC reaction, this method exhibits high sensitivity and selectivity for the detection of tumor-derived exosomal miRNAs in situ. Moreover, due to its excellent performance, this logic device can effectively distinguish liver cancer patients from healthy donors by determining the amount of cancer-cell-derived exosomal miRNAs. Overall, this strategy has great potential for analyzing various types of exosomes and provides a viable tool to improve the accuracy of cancer diagnosis.
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Exosomas , Neoplasias Hepáticas , Nanopartículas del Metal , MicroARNs , Humanos , MicroARNs/genética , Oro , Entropía , Exosomas/genética , ADN , Neoplasias Hepáticas/diagnóstico , LógicaRESUMEN
Shape memory hydrogels provide a worldwide scope for functional soft materials. However, most shape memory hydrogels exhibit poor mechanical properties, leading to low actuation strength, which severely limits their applications in smart biomimetic devices. Herein, a strategy for muscle-inspired shape memory-oriented polyvinyl alcohol (PVA)-natural rubber latex (NRL) hydrogel (OPNH) with multiscale oriented structure is demonstrated. The shape memory function comes from the stretch-induced crystallization of natural rubber (NR), while PVA forms strong hydrogen bonding interactions with proteins and phospholipids on the surface of NRL particles. Meanwhile, the reconfigurable interactions of PVA and NR produce a multiscale-oriented structure during stretch-drying, improving the mechanical and shape memory properties. The resultant OPNH shows excellent interfacial compatibility, exhibiting outstanding mechanical performance (3.2 MPa), high shape fixity (≈80%) and shape recovery ratio (≈92%), high actuation strength (206 kPa), working capacity (105 kJ m- 3), extremely short response time (≈2 s), low response temperature (28 °C) and smart thermal responsiveness. It can even maintain muscle-like working capacity when lifting a load equivalent to 372 times its weight, providing a new class shape memory material for the application in smart biomimetic muscles and multistimulus responsive devices.
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High-speed optical polarization characterization is highly desirable for a wide range of applications, including remote sensing, telecommunication, and medical diagnosis. The utilization of the Mueller matrix provides a superior systematic and comprehensive approach to represent polarization attributes when matter interacts with optical beams. However, the current measurement speed of Mueller matrix is limited to only seconds or milliseconds. In this study, we present an ultrafast Mueller matrix polarimetry (MMP) technique based on optical time-stretch and spectral encoding that enables us to achieve an impressive temporal resolution of 4.83 nanoseconds for accurate Mueller matrix measurements. The unique feature of optical time-stretch technology enables continuous, ultrafast single-shot spectroscopy, resulting in a remarkable speed of up to 207 MHz for spectral encoding Mueller matrix measurement. We have employed an effective Mueller linear reconstruction algorithm based on the measured modulation matrix, accounting for all potential non-ideal effects of polarization components like retardance error and azimuth error. To ensure high precision, prior to the actual measurement, high-order dispersion induced by time-stretch requires adjustment through proper modulation matrix design. Upon such correction, both the results of static and rapid dynamic samples measurements exhibit exceptional accuracy with root-mean-square error (RMSE) approximately equal to 0.04 and 0.07 respectively. This presented ultrafast MMP provides a significant advance over preceding endeavors, enabling superior accuracy and increased speed concurrently.
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An ultra-low-complexity third-order weight-sharing trigonometric nonlinear equalizer (WS-TNLE) is proposed to eliminate nonlinear signal distortions in short-reach optical interconnects exceeding net 200â Gb/s/λ. By replacing the second- and third-order nonlinear terms in a third-order weight-sharing diagonally pruned Volterra nonlinear equalizer (WS-DP-VNLE) with cosine and sine terms, respectively, the required number of real-valued multiplications per symbol of the proposed third-order WS-TNLE is significantly reduced to the same value as the number of weight-sharing kernels. When transmitting probabilistically shaped 16-level pulse amplitude modulation (PS-PAM-16) signals at net rates ranging from 200.4â Gb/s to 300.4â Gb/s over a 1-km standard single-mode fiber (SSMF), the proposed third-order WS-TNLE requires the lowest number of real-valued multiplications per symbol, ranging from 10 to 44, which reduces the computational complexity by up to 96.2% and 52.4% compared to the third-order WS-DP-VNLE and WS-DP-absolute-term nonlinear equalizer (WS-DP-ATNLE), respectively.
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The generation mechanism and regulation method of the radial higher-order orbital angular momentum (OAM) mode based on helically twisted elliptic fiber (HTEF) are investigated. This work aims to reveal the quantitative relation between the twisted rate (α) and the target radial higher-order OAM mode. From theoretical simulations, it is concluded that α is the key to regulating the radial higher-order OAM mode. In the experiment, OAM2n modes with radial higher-order n of 2, 3, 4, and 5 are successfully generated at 1550 nm by regulating α of the HTEF. Finally, the transmission spectrum and purity measurements are performed for the OAM24 mode, and it can be concluded that the fabricated experimental samples have more than 90% conversion efficiency and close to 94% purity under the appropriate α and twisted length.
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In this Letter, we experimentally investigate a non-line-of-sight (NLOS) optical wireless communication (OWC) system that utilizes wavefront shaping techniques to realize simultaneous data transmission for multiple users. Wavefront shaping techniques are employed to address the issue of low intensity of diffusely reflected light at the receiver in NLOS scenarios for indoor high-speed access. To achieve communication path planning and tracing for two different users in free-space optical communication, the pixels of the spatial light modulator (SLM) are divided into two halves to separately manipulate the wavefront of two independent data carriers centered at different wavelengths. The maximum received optical power can be effectively improved by more than 15â dB with the wavefront shaping technique. To avoid power enhancement of non-target wavelength, the wavelength difference of two different users is experimentally studied. The difference in power enhancement ratio (DPER) is increased with the wavelength difference, and 14.95â dB DPER is obtained with a 10â nm wavelength difference. Under the aforementioned wavelength planning strategy, successful transmission and reception of 2 × 160â Gbit/s 16-QAM signals for two users with coherent detection is achieved using wavelengths of 1550 and 1560â nm in an indoor access scenario.
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Chalcogenide glasses (ChGs) possess a high elasto-optic coefficient, making them ideal for applications in microwave photonics and narrow-linewidth lasers based on stimulated Brillouin scattering (SBS). However, current As2S3-based integrated devices suffer from poor stability and low laser-induced damage threshold, and planar ChG devices feature limited quality factors. In this Letter, we propose and demonstrate a high-quality integrated GeSbS ChG Brillouin photonic device. By introducing Euler bending structures, we suppress high-order optical modes and reduce propagation losses in a finger-shaped GeSbS microresonator, resulting in a compact footprint of 3.8 mm2 and a high intrinsic quality factor of 5.19 × 106. The combination of GeSbS material's high Brillouin gain and the resonator's high-quality factor enables the generation of stimulated Brillouin lasers with a low threshold of 0.96 mW and a fundamental linewidth of 58 Hz. Moreover, cascaded stimulated Brillouin lasers can be realized up to the seventh order, yielding microwave beat frequencies up to 40 GHz.
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This paper reports an optical strain sensor that integrates a self-powered mechanoluminescent (ML) elastic fiber with a flexible circuit. The inclusion of an alumina nanoparticle as the additive results in seven-fold enhancement of ML intensity while maintaining flexibility of 120% strain. The sensor facilitates the detection of strain and stretching speed. It attains a sensitivity of 0.0022â lx/(1% strain) and a resolution of 0.2% strain, respectively. We have successfully applied it to detect bending motions of the finger, wrist, and elbow. This wearable strain sensor holds promise for diverse applications in wearable technology.
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BACKGROUND: The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). PURPOSE: To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. STUDY TYPE: Prospective. SUBJECTS: Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. ASSESSMENT: Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. STATISTICAL TESTS: Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. RESULTS: Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. DATA CONCLUSION: Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.
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Enfermedad de Alzheimer , Circulación Cerebrovascular , Disfunción Cognitiva , Ayuno , Imagen por Resonancia Magnética , Periodo Posprandial , Marcadores de Spin , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Femenino , Masculino , Circulación Cerebrovascular/fisiología , Anciano , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Disfunción Cognitiva/diagnóstico por imagen , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Diagnóstico DiferencialRESUMEN
PURPOSE: To investigate the capacity of critical flicker frequency (CFF) in discriminating cataract eyes with or without macula disease using trichromatic flickers, and to develop a model to predict postoperative best corrected visual acuity (BCVA). METHODS: Patients were divided into two groups based on the presence or absence of macular disease. CFF threshold measurements of red (R-CFF), green (G-CFF), and yellow (Y-CFF) flickers were conducted both preoperatively and postoperatively. A generalized estimating equations model (GEE) was employed to examine the relationship between CFF threshold and 3-month postoperative BCVA. RESULTS: A total of 115 eyes were enrolled, with 59 eyes in the cataract alone group and 56 eyes in the cataract with macular disease group completing the follow-up. R-CFF was found to be consistent before and after cataract removal (P = 0.06), even in cases where OCT was not performed successfully (P > 0.05). Y-CFF showed the highest AUC (0.798) for differentiating ocular comorbidities. According to the GEE model, in patients with a CFF threshold below 26 Hz, the odds ratios for achieving a postoperative VA of 20/40 or better were 34.8% for R-CFF, 26.0% for G-CFF, and 24.5% for Y-CFF. CONCLUSION: CFF emerges as a promising tool for predicting postoperative BCVA, providing valuable supplementary insights when fundus examination is obstructed. R-CFF demonstrates the best resistance to cataracts, while Y-CFF exhibits the highest sensitivity both in identifying macular diseases and predicting postoperative BCVA of 20/40 or better.
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Catarata , Agudeza Visual , Humanos , Femenino , Masculino , Catarata/fisiopatología , Catarata/complicaciones , Catarata/diagnóstico , Agudeza Visual/fisiología , Anciano , Persona de Mediana Edad , Mácula Lútea/fisiopatología , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/patología , Estudios de Seguimiento , Enfermedades de la Retina/fisiopatología , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia Óptica/métodos , Curva ROC , Estudios Prospectivos , Pruebas de Visión/métodosRESUMEN
BACKGROUND: Human papillomavirus (HPV) infection is an important factor leading to cervical cell abnormalities. 90% of cervical cancers are closely associated with persistent infection of high-risk HPV, with the highest correlation with HPV16 and 18. Currently available vaccines and antivirals have limited effectiveness and coverage. Guanylate binding protein 1 (GBP1) was induced by interferon gamma and involved in many important cellular processes such as clearance of various microbial pathogens. However, whether GBP1 can inhibit human papillomavirus infection is unclear. RESULTS: In this study, we found that GBP1 can effectively degrade HPV18 E6, possibly through its GTPase activity or other pathways, and E6 protein degrades GBP1 through the ubiquitin-proteasome pathway to achieve immune escape. CONCLUSION: Therefore, GBP1 is an effector of IFN-γ anti-HPV activity. Our findings provided new insights into the treatment of HPV 18 infections.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Proteínas de Unión al GTP , Papillomavirus Humano 18 , Interferón gamma/farmacologíaRESUMEN
PURPOSE: This study aimed to use MRI histogram analysis to routine MRI sequences to evaluate lumbar disc degeneration (LDD), illustrate the correlation between this novel method and the traditional Pfirrmann classification method, and more importantly, perform comprehensive agreement analysis of MRI histogram analysis in various situations to evaluate its objectivity and stability. METHODS: Lumbar MRI images from 133 subjects were included in this study. LDD was classified into grades by Pfirrmann classification and was measured as peak separation value by MRI histogram analysis. Correlation analysis between the two methods was performed and cutoff values were determined. In addition, the agreement analysis of peak separation value was performed by intraclass correlation coefficient (ICC) in four scenarios, including inter-resolution, inter-observer, inter-regions of interest (ROI) and inter-slice. RESULTS: Peak separation values were strongly correlated with Pfirrmann grades (r = - 0.847). The inter-resolution agreements of peak separation value between original image resolution of 2304 × 2304 and compressed image resolutions (1152 × 1152, 576 × 576, 288 × 288) were good to excellent (ICCs were 0.916, 0.876 and 0.822), except 144 × 144 was moderate (ICC = 533). The agreements of inter-observer (ICC = 0.982) and inter-ROI (ICC = 0.915) were excellent. Compared with the mid-sagittal slice, the inter-slice agreements were good for the first adjacent slices (ICCs were 0.826 and 0.844), and moderate to good for the second adjacent slices (ICC = 0.733 and 0.753). CONCLUSION: MRI histogram analysis, used in routine MRI sequences, demonstrated a strong correlation with Pfirrmann classification and good agreements in various scenarios, expanding the range of application and providing an effective, objective and quantitative tool to evaluate LDD.
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Degeneración del Disco Intervertebral , Vértebras Lumbares , Imagen por Resonancia Magnética , Humanos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Vértebras Lumbares/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Adulto , Anciano , Adulto JovenRESUMEN
OBJECTIVE: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. METHODS: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. RESULTS: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001). CONCLUSIONS: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.
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Factor Activador de Células B , Progresión de la Enfermedad , Glomerulonefritis Membranosa , Proteinuria , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Humanos , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/diagnóstico , Factor Activador de Células B/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Pronóstico , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/sangre , Proteinuria/sangre , Proteinuria/etiología , Modelos de Riesgos Proporcionales , Receptores de Fosfolipasa A2/inmunología , Receptores de Fosfolipasa A2/sangre , Estudios de Casos y Controles , Anciano , Tasa de Filtración Glomerular , Riñón/fisiopatología , Riñón/patologíaRESUMEN
Chalcogenide glasses (ChGs) have recently emerged as enabling materials for building reconfigurable nanophotonic devices by employing their refractive index changes associated with photosensitive effects. In particular, the availability of low-loss thin-film ChGs and the realization of high-Q microresonators provide exciting opportunities for integrated photonics. So far, the ChG photonic devices are predominately operated in the classical optics regime. In this work, we present the realization on-chip bright photon-pair quantum light sources via spontaneous four-wave mixing in a high-Q microring resonator fabricated on the newly developed ChG Ge25Sb10S65 platform. The emission wavelength of the photon-pair source can be continuously tuned across a double-free spectral range in a reconfigurable manner. Our work serves as a starting point to fully unleash the potential of exploiting ChGs for developing reconfigurable integrated quantum photonic devices.