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Iron deposition is frequently observed in human autoinflammatory diseases, but its functional significance is largely unknown. Here we showed that iron promoted proinflammatory cytokine expression in T cells, including GM-CSF and IL-2, via regulating the stability of an RNA-binding protein PCBP1. Iron depletion or Pcbp1 deficiency in T cells inhibited GM-CSF production by attenuating Csf2 3' untranslated region (UTR) activity and messenger RNA stability. Pcbp1 deficiency or iron uptake blockade in autoreactive T cells abolished their capacity to induce experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Mechanistically, intracellular iron protected PCBP1 protein from caspase-mediated proteolysis, and PCBP1 promoted messenger RNA stability of Csf2 and Il2 by recognizing UC-rich elements in the 3' UTRs. Our study suggests that iron accumulation can precipitate autoimmune diseases by promoting proinflammatory cytokine production. RNA-binding protein-mediated iron sensing may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.
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Proteínas Portadoras/metabolismo , Citocinas/biosíntesis , Encefalomielitis Autoinmune Experimental/metabolismo , Hierro/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/patología , Regiones no Traducidas 3' , Animales , Sitios de Unión , Línea Celular , Citocinas/genética , Proteínas de Unión al ADN , Encefalomielitis Autoinmune Experimental/patología , Femenino , Humanos , Hierro/agonistas , Deficiencias de Hierro , Ratones , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Procesamiento Postranscripcional del ARN , Estabilidad del ARN/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño , Proteínas de Unión al ARN , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Receptores de Transferrina/deficiencia , Linfocitos T Colaboradores-Inductores/trasplanteRESUMEN
A growing body of research demonstrates that distracting inputs can be proactively suppressed via spatial cues, nonspatial cues, or experience, which are governed by more than one top-down mechanism of attention. However, how the neural mechanisms underlying spatial distractor cues guide proactive suppression of distracting inputs remains unresolved. Here, we recorded electroencephalography signals from 110 participants in 3 experiments to identify the role of alpha activity in proactive distractor suppression induced by spatial cues and its influence on subsequent distractor inhibition. Behaviorally, we found novel changes in the spatial proximity of the distractor: Cueing distractors far away from the target improves search performance for the target, while cueing distractors close to the target hampers performance. Crucially, we found dynamic characteristics of spatial representation for distractor suppression during anticipation. This result was further verified by alpha power increased relatively contralateral to the cued distractor. At both the between- and within-subjects levels, we found that these activities further predicted the decrement of the subsequent PD component, which was indicative of reduced distractor interference. Moreover, anticipatory alpha activity and its link with the subsequent PD component were specific to the high predictive validity of distractor cue. Together, our results reveal the underlying neural mechanisms by which cueing the spatial distractor may contribute to reduced distractor interference. These results also provide evidence supporting the role of alpha activity as gating by proactive suppression.
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Señales (Psicología) , Electroencefalografía , Humanos , Atención/fisiología , Inhibición Psicológica , Tiempo de Reacción/fisiología , Percepción Visual/fisiologíaRESUMEN
RNA splicing is a critical mechanism by which to modify transcriptome, and its dysregulation is the underlying cause of many human diseases. It remains challenging, however, to genetically modulate a splicing event in its native context. Here, we demonstrate that a CRISPR-guided cytidine deaminase (i.e., targeted-AID mediated mutagenesis [TAM]) can efficiently modulate various forms of mRNA splicing. By converting invariant guanines to adenines at either 5' or 3' splice sites (SS), TAM induces exon skipping, activation of alternative SS, switching between mutually exclusive exons, or targeted intron retention. Conversely, TAM promotes downstream exon inclusion by mutating cytidines into thymines at the polypyrimidine tract. Applying this approach, we genetically restored the open reading frame and dystrophin function of a mutant DMD gene in patient-derived induced pluripotent stem cells (iPSCs). Thus, the CRISPR-guided cytidine deaminase provides a versatile genetic platform to modulate RNA splicing and to correct mutations associated with aberrant splicing in human diseases.
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Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Citidina Desaminasa/genética , Empalme del ARN/genética , Secuencia de Aminoácidos , Animales , Línea Celular , Distrofina/genética , Exones/genética , Redes Reguladoras de Genes , Células HEK293 , Humanos , Intrones/genética , Ratones , Sistemas de Lectura Abierta/genética , Sitios de Empalme de ARN/genéticaRESUMEN
PSMD4/Rpn10 is a subunit of the 19S proteasome unit that is involved with feeding target proteins into the catalytic machinery of the 26S proteasome. Because proteasome inhibition is a common therapeutic strategy in multiple myeloma (MM), we investigated Rpn10 and found that it is highly expressed in MM cells compared with normal plasma cells. Rpn10 levels inversely correlated with overall survival in patients with MM. Inducible knockout or knockdown of Rpn10 decreased MM cell viability both in vitro and in vivo by triggering the accumulation of polyubiquitinated proteins, cell cycle arrest, and apoptosis associated with the activation of caspases and unfolded protein response-related pathways. Proteomic analysis revealed that inhibiting Rpn10 increased autophagy, antigen presentation, and the activation of CD4+ T and natural killer cells. We developed an in vitro AlphaScreen binding assay for high-throughput screening and identified a novel Rpn10 inhibitor, SB699551 (SB). Treating MM cell lines, leukemic cell lines, and primary cells from patients with MM with SB decreased cell viability without affecting the viability of normal peripheral blood mononuclear cells. SB inhibited the proliferation of MM cells even in the presence of the tumor-promoting bone marrow milieu and overcame proteasome inhibitor (PI) resistance without blocking the 20S proteasome catalytic function or the 19S deubiquitinating activity. Rpn10 blockade by SB triggered MM cell death via similar pathways as the genetic strategy. In MM xenograft models, SB was well tolerated, inhibited tumor growth, and prolonged survival. Our data suggest that inhibiting Rpn10 will enhance cytotoxicity and overcome PI resistance in MM, providing the basis for further optimization studies of Rpn10 inhibitors for clinical application.
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Mieloma Múltiple , Complejo de la Endopetidasa Proteasomal , Humanos , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina/metabolismo , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Proteómica , Leucocitos Mononucleares/metabolismo , Proteínas Portadoras/genética , Proteínas/metabolismo , Proteínas de Unión al ARNRESUMEN
Metastasis is the primary cause of cancer-related deaths and remains poorly understood. Deubiquitinase OTU domain containing 4 (OTUD4) has been reported to regulate antiviral immune responses and resistance to radio- or chemo-therapies in certain cancers. However, the role of OTUD4 in cancer metastasis remain unknown. Here, we demonstrate that the depletion of OTUD4 in triple-negative breast cancer (TNBC) cells markedly suppress cell clonogenic ability, migration, invasion and cancer stem cell population in vitro as well as metastasis in vivo. Mechanistically, the tumor promoting function of OTUD4 is mainly mediated by deuiquitinating and stabilizing Snail1, one key transcriptional factor in the epithelial-mesenchymal transition. The inhibitory effect of targeting OTUD4 could be largely reversed by the reconstitution of Snail1 in OTUD4-deficient cells. Overall, our study establishes the OTUD4-Snail1 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of TNBC.
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Factores de Transcripción de la Familia Snail , Neoplasias de la Mama Triple Negativas , Proteasas Ubiquitina-Específicas , Proteasas Ubiquitina-Específicas/metabolismo , Células MDA-MB-231 , Células HEK293 , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/fisiopatología , Metástasis de la Neoplasia/genética , Factores de Transcripción de la Familia Snail/metabolismo , Humanos , Femenino , Animales , Ratones , Movimiento Celular/genética , Invasividad Neoplásica/genética , Estabilidad ProteicaRESUMEN
In recent years, brain imaging genomics has advanced significantly in revealing underlying pathological mechanisms of Alzheimer's disease (AD) and providing early diagnosis. In this paper, we present a framework for diagnosing AD that integrates magnetic resonance imaging (fMRI) genetic preprocessing, feature selection, and a support vector machine (SVM) model. In particular, a novel sand cat swarm optimization (SCSO) algorithm, named SS-SCSO, which integrates the spiral search strategy and alert mechanism from the sparrow search algorithm, is proposed to optimize the SVM parameters. The optimization efficacy of the SS-SCSO algorithm is evaluated using CEC2017 benchmark functions, with results compared with other metaheuristic algorithms (MAs). The proposed SS-SCSO-SVM framework has been effectively employed to classify different stages of cognitive impairment in Alzheimer's Disease using imaging genetic datasets from the Alzheimer's Disease Neuroimaging Initiative. It has demonstrated excellent classification accuracies for four typical cases, including AD, early mild cognitive impairment, late mild cognitive impairment, and healthy control. Furthermore, experiment results indicate that the SS-SCSO-SVM algorithm has a stronger exploration capability for diagnosing AD compared to other well-established MAs and machine learning techniques.
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Algoritmos , Enfermedad de Alzheimer , Imagen por Resonancia Magnética , Máquina de Vectores de Soporte , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Genómica de Imágenes/métodos , Neuroimagen/métodos , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/genética , Masculino , Anciano , FemeninoRESUMEN
While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.
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Atención , Percepción Auditiva , Electroencefalografía , Percepción Visual , Humanos , Atención/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Percepción Auditiva/fisiología , Percepción Visual/fisiología , Estimulación Acústica/métodos , Estimulación Luminosa/métodos , Potenciales Evocados/fisiología , Encéfalo/fisiología , AdolescenteRESUMEN
Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational framework consisting of outrigger, a de novo splice graph transversal algorithm to detect AS; anchor, a Bayesian approach to assign modalities; and bonvoyage, a visualization tool using non-negative matrix factorization to display modality changes. Applying Expedition to single pluripotent stem cells undergoing neuronal differentiation, we discover that up to 20% of AS exons exhibit bimodality. Bimodal exons are flanked by more conserved intronic sequences harboring distinct cis-regulatory motifs, constitute much of cell-type-specific splicing, are highly dynamic during cellular transitions, preserve reading frame, and reveal intricacy of cell states invisible to conventional gene expression analysis. Systematic AS characterization in single cells redefines our understanding of AS complexity in cell biology.
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Empalme Alternativo , Proteínas del Tejido Nervioso/biosíntesis , Células-Madre Neurales/metabolismo , Neurogénesis , Neuronas/metabolismo , Células Madre Pluripotentes/metabolismo , ARN Mensajero/metabolismo , Análisis de la Célula Individual , Algoritmos , Teorema de Bayes , Línea Celular , Simulación por Computador , Evolución Molecular , Regulación del Desarrollo de la Expresión Génica , Humanos , Cinética , Masculino , Modelos Genéticos , Proteínas del Tejido Nervioso/genética , Fenotipo , ARN Mensajero/genéticaRESUMEN
Water, covering over two-thirds of the Earth's surface, holds immense potential for generating clean water, sustainable energy, and metal resources, which are the cornerstones of modern society and future development. It is highly desired to produce these crucial elements through eco-friendly processes with minimal carbon footprints. Interfacial solar evaporation, which utilizes solar energy at the air-liquid interface to facilitate water vaporization and solute separation, offers a promising solution. In this review, we systematically report the recent progress of the cogeneration of clean water and energy/resources including electricity, hydrogen, and metal resources via interfacial solar evaporation. We first gain insight into the energy and mass transport for a typical interfacial solar evaporation system and reveal the residual energy and resources for achieving the cogeneration goal. Then, we summarize the recent advances in materials/device designs for efficient cogeneration. Finally, we discuss the existing challenges and potential opportunities for the further development of this field.
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To cope with flooding-induced hypoxia, plants have evolved different strategies. Molecular strategies, such as the N-degron pathway and transcriptional regulation, are known to be crucial for Arabidopsis thaliana's hypoxia response. Our study uncovered a novel molecular strategy that involves a single transcription factor interacting with two identical cis-elements, one located in the promoter region and the other within the intron. This unique double-element adjustment mechanism has seldom been reported in previous studies. In humid areas, WRKY70 plays a crucial role in A. thaliana's adaptation to submergence-induced hypoxia by binding to identical cis-elements in both the promoter and intron regions of WRKY33. This dual binding enhances WRKY33 expression and the activation of hypoxia-related genes. Conversely, in arid regions lacking the promoter cis-element, WRKY70 only binds to the intron cis-element, resulting in limited WRKY33 expression during submergence stress. The presence of a critical promoter cis-element in humid accessions, but not in dry accessions, indicates a coordinated regulation enabling A. thaliana to adapt and thrive in humid habitats.
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Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regiones Promotoras Genéticas/genética , Hipoxia/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
Hybrid halide perovskites are good candidates for a range of functional materials such as optical electronic and photovoltaic devices due to their tunable band gaps, long carrier diffusion lengths, and solution processability. However, the instability in moisture/air, the toxicity of lead, and rigorous reaction setup or complex postprocessing have long been the bottlenecks for practical application. Herein, we present a simultaneous configurational entropy design at A-sites, B-sites, and X-sites in the typical (CHA)2PbBr4 two-dimensional (2D) hybrid perovskite. Our results demonstrate that the high-entropy effect favors the stabilization of the hybrid perovskite phase and facilitates a simple crystallization process without precise control of the cooling rate to prepare regular crystals. Moreover, high-entropy 2D perovskite crystals exhibit tunable energy band gaps, broadband emission, and a long carrier lifetime. Meanwhile, the high-entropy composition almost maintains the initial crystal structure in deionized water for 18 h while the original (CHA)2PbBr4 crystal mostly decomposes, suggesting obviously improved humidity stability. This work offers a facile approach to synthesize humidity-stable hybrid perovskites under mild conditions, accelerating relevant preparation of optoelectronics and light-emitting devices and facilitating the ultimate commercialization of halide perovskite.
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INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.
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Benzofuranos , Neoplasias Colorrectales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Benzofuranos/efectos adversos , Benzofuranos/uso terapéutico , Benzofuranos/administración & dosificación , Adulto , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Quinazolinas/administración & dosificación , China , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Pueblos del Este de AsiaRESUMEN
Histone methylation is a key epigenetic modification that regulates the chromatin structure and gene expression for proper cellular and physiological processes. Aberrant histone methylation patterns are implicated in many diseases. Therefore, monitoring histone methylation dynamics in living cells and species is essential for elucidating its regulatory mechanisms and identifying potential therapeutic targets. However, current methods for detecting histone methylation are limited by their low sensitivity and specificity. To overcome this challenge, we have developed a genetically encoded biosensor named Phaser-Trim (Phase separation based genetically encoded reporter for H3K9 Trimethylation) to detect the dynamic changes of H3K9me3 in living cells and species through the generation and disappearance of phase-separated droplets. Phaser-Trim demonstrates advantages of clear phenotypic characteristics, convenient operation, quantitative accuracy, biocompatibility, high specificity, and superior imaging performance with high signal-to-background ratio (SBR) for in vivo animal imaging. Using Phaser-Trim, we have successfully detected the dynamics of the H3K9me3 level during the differentiation of neural stem cells in Drosophila. Furthermore, Phaser-Trim also holds promise for application in high-throughput screening systems to facilitate the discovery of novel anticancer drugs.
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Histonas , Histonas/metabolismo , Histonas/química , Animales , Metilación , Humanos , Técnicas Biosensibles/métodos , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Drosophila , Diferenciación Celular , Separación de FasesRESUMEN
The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTSâ¢+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.
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Toxinas Bacterianas , Técnicas Biosensibles , Técnicas Electroquímicas , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/análisis , Estructuras Metalorgánicas/química , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Peroxidasa/metabolismo , Peroxidasa/química , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/metabolismoRESUMEN
Large-capacity energy storage devices are attracting widespread research attention. However, the decreased capacity of these devices due to cold weather is a huge obstacle for their practical use. In this study, an electrochemical self-adaptive reconstructed Cux S/Cu(OH)2 -based symmetric energy storage device is proposed. This device provides a satisfactorily enhanced photothermal capacity under solar irradiation. After electrochemical reconstruction treatment, the morphological structure is rearranged and the Cux S component is partially converted to electrochemically active Cu(OH)2 with the introduction of a large number of active sites. The resulting Cux S/Cu(OH)2 electrode provides a significant capacitance of 115.2 F cm-2 at 5 mA cm-2 . More importantly, its wide working potential range and superior photo-to-thermal conversion ability endow Cux S/Cu(OH)2 with superb performance as full-purpose photothermally enhanced capacitance electrodes. Under solar irradiation, the surface temperature of Cux S/Cu(OH)2 is elevated by 76.6 °C in only 30 s, and the capacitance is boosted to 230.4% of the original capacitance at a low temperature. Furthermore, the assembled symmetric energy storage device also delivers a photothermal capacitance enhancement of 200.3% under 15 min solar irradiation.
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PURPOSE: This study aims to assess ultrashort-TE magnetization transfer (UTE-MT) imaging of collagen degradation using an in vitro model of rotator cuff tendinopathy. METHODS: Thirty-six supraspinatus tendon specimens were divided into three groups and treated with 600 U collagenase (Group 1), 150 U collagenase (Group 2), and phosphate buffer saline (Group 3). UTE-MT imaging was performed to assess changes in macromolecular fraction (MMF), macromolecule transverse relaxation time (T2m), water longitudinal relaxation rate constant (R1m), the magnetization exchange rate from the macromolecular to water pool (Rm0 w) and from water to the macromolecular pool (Rm0 m), and magnetization transfer ratio (MTR) at baseline and following digestion and their differences between groups. Biochemical and histological studies were conducted to determine the extent of collagen degradation. Correlation analyses were performed with MMF, T2m, R1m, Rm0 w, Rm0 m, and MTR, respectively. Univariate and multivariate linear regression analyses were performed to evaluate combinations of UTE-MT parameters to predict collagen degradation. RESULTS: MMF, T2m, R1m, Rm0 m, and MTR decreased after digestion. MMF (r = -0.842, p < 0.001), MTR (r = -0.78, p < 0.001), and Rm0 m (r = -0.662, p < 0.001) were strongly negatively correlated with collagen degradation. The linear regression model of differences in MMF and Rm0 m before and after digestion explained 68.9% of collagen degradation variation in the tendon. The model of postdigestion in MMF and T2m and the model of MTR explained 54.2% and 52.3% of collagen degradation variation, respectively. CONCLUSION: This study highlighted the potential of UTE-MT parameters for evaluation of supraspinatus tendinopathy.
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Colágeno , Imagen por Resonancia Magnética , Manguito de los Rotadores , Tendinopatía , Tendinopatía/diagnóstico por imagen , Tendinopatía/metabolismo , Colágeno/metabolismo , Humanos , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Colagenasas/metabolismo , Tendones/diagnóstico por imagen , Tendones/metabolismo , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Accurate measurement of the dielectric functions of emerging optical materials is of great importance for advancements in solid-state physics. However, it is rather challenging since most materials are highly active in ambient conditions, which makes in-situ measurements tough. Here, we report an analytical ellipsometry method (AEM) accessible in ambient conditions for measuring the dielectric functions of chemically reactive materials under bulk encapsulation. Taking the highly pursued low-loss plasmonic materials, such as sodium films, as an example, the effectiveness and measuring errors of the proposed AEM have been systematically demonstrated. This verifies AEM's superiority in overcoming the limitations of traditional spectroscopic ellipsometry methodologies, which include complex multi-parameter fitting procedures and the issue of potentially unphysical results, especially in newly developed low-loss materials. Our results will provide a generalized and convenient ellipsometric measurement strategy for sensitive materials under bulk encapsulation.
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Compressed ultrafast photography (CUP) is a computational imaging technology capable of capturing transient scenes in picosecond scale with a sequence depth of hundreds of frames. Since the inverse problem of CUP is an ill-posed problem, it is challenging to further improve the reconstruction quality under the condition of high noise level and compression ratio. In addition, there are many articles adding an external charge-coupled device (CCD) camera to the CUP system to form the time-unsheared view because the added constraint can improve the reconstruction quality of images. However, since the images are collected by different cameras, slight affine transformation may have great impacts on the reconstruction quality. Here, we propose an algorithm that combines the time-unsheared image constraint CUP system with unsupervised neural networks. Image registration network is also introduced into the network framework to learn the affine transformation parameters of input images. The proposed algorithm effectively utilizes the implicit image prior in the neural network as well as the extra hardware prior information brought by the time-unsheared view. Combined with image registration network, this joint learning model enables our proposed algorithm to further improve the quality of reconstructed images without training datasets. The simulation and experiment results demonstrate the application prospect of our algorithm in ultrafast event capture.
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This paper present a novel, integrated compressed ultrafast photography system for comprehensive measurement of the aluminium planar wire array Z-Pinch evolution process. The system incorporates a large array streak camera and embedded encoding to improve the signal-to-noise ratio. Based on the "QiangGuang-I" pulsed power facility, we recorded the complete continuous 2D implosion process of planar wire array Z-Pinch for the first time. Our results contribute valuable understanding of imploding plasma instabilities and offer direction for the optimization of Z-Pinch facilities.
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Oxygen deprivation caused by flooding activates acclimation responses to stress and restricts plant growth. After experiencing flooding stress, plants must restore normal growth; however, which genes are dynamically and precisely controlled by flooding stress remains largely unknown. Here, we show that the Arabidopsis thaliana ubiquitin E3 ligase SUBMERGENCE RESISTANT1 (SR1) regulates the stability of the transcription factor WRKY33 to modulate the submergence response. SR1 physically interacts with WRKY33 in vivo and in vitro and controls its ubiquitination and proteasomal degradation. Both the sr1 mutant and WRKY33 overexpressors exhibited enhanced submergence tolerance and enhanced expression of hypoxia-responsive genes. Genetic experiments showed that WRKY33 functions downstream of SR1 during the submergence response. Submergence induced the phosphorylation of WRKY33, which enhanced the activation of RAP2.2, a positive regulator of hypoxia-response genes. Phosphorylated WRKY33 and RAP2.2 were degraded by SR1 and the N-degron pathway during reoxygenation, respectively. Taken together, our findings reveal that the on-and-off module SR1-WRKY33-RAP2.2 is connected to the well-known N-degron pathway to regulate acclimation to submergence in Arabidopsis. These two different but related modulation cascades precisely balance submergence acclimation with normal plant growth.