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CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and ß-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context, the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. These findings reveal how 3D chromosome architecture can be encoded by linear genome sequences.
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Cromosomas/metabolismo , Técnicas Genéticas , Proteínas Represoras/metabolismo , Animales , Sitios de Unión , Factor de Unión a CCCTC , Cadherinas/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Cromosomas/química , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , ADN/química , Elementos de Facilitación Genéticos , Expresión Génica , Genoma Humano , Humanos , Células K562 , Ratones , Regiones Promotoras Genéticas , Globinas beta/genética , CohesinasRESUMEN
The extensive use of nitrogen fertilizer boosts rice (Oryza sativa) production but also harms ecosystems. Therefore, enhancing crop nitrogen use efficiency is crucial. Here, we performed map-based cloning and identified the EARLY FLOWERING3 (ELF3) like protein-encoding gene OsELF3-1, which confers enhanced nitrogen uptake in rice. OsELF3-1 forms a ternary complex (OsEC) with OsELF4s and OsLUX, the putative orthologs of ELF4 and LUX ARRHYTHMO (LUX) in Arabidopsis (Arabidopsis thaliana), respectively. OsEC directly binds to the promoter of Grain number, plant height, and heading date7 (Ghd7) and represses its expression. Ghd7 encodes a transcription factor that has major effects on multiple agronomic traits. Ghd7 is also a transcriptional repressor and directly suppresses the expression of ABC1 REPRESSOR1 (ARE1), a negative regulator of nitrogen use efficiency. Therefore, targeting the OsEC-Ghd7-ARE1 module offers an approach to enhance nitrogen uptake, presenting promising avenues for sustainable agriculture.
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Human gustatory system recognizes salty/sour or sweet tastants based on their different ionic or nonionic natures using two different signaling pathways. This suggests that evolution has selected this detection dualism favorably. Analogically, this work constructs herein bioinspired stimulus-responsive hydrogels to recognize model salty/sour or sweet tastes based on two different responses, that is, electrical and volumetric responsivities. Different compositions of zwitter-ionic sulfobetainic N-(3-sulfopropyl)-N-(methacryloxyethyl)-N,N-dimethylammonium betaine (DMAPS) and nonionic 2-hydroxyethyl methacrylate (HEMA) are co-polymerized to explore conditions for gelation. The hydrogel responses upon adding model tastant molecules are explored using electrical and visual de-swelling observations. Beyond challenging electrochemical impedance spectroscopy measurements, naive multimeter electrical characterizations are performed, toward facile applicability. Ionic model molecules, for example, sodium chloride and acetic acid, interact electrostatically with DMAPS groups, whereas nonionic molecules, for example, D(-)fructose, interact by hydrogen bonding with HEMA. The model tastants induce complex combinations of electrical and volumetric responses, which are then introduced as inputs for machine learning algorithms. The fidelity of such a trained dual response approach is tested for a more general taste identification. This work envisages that the facile dual electric/volumetric hydrogel responses combined with machine learning proposes a generic bioinspired avenue for future bionic designs of artificial taste recognition, amply needed in applications.
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Updated and expert-quality knowledge bases are fundamental to biomedical research. A knowledge base established with human participation and subject to multiple inspections is needed to support clinical decision making, especially in the growing field of precision oncology. The number of original publications in this field has risen dramatically with the advances in technology and the evolution of in-depth research. Consequently, the issue of how to gather and mine these articles accurately and efficiently now requires close consideration. In this study, we present OncoPubMiner (https://oncopubminer.chosenmedinfo.com), a free and powerful system that combines text mining, data structure customisation, publication search with online reading and project-centred and team-based data collection to form a one-stop 'keyword in-knowledge out' oncology publication mining platform. The platform was constructed by integrating all open-access abstracts from PubMed and full-text articles from PubMed Central, and it is updated daily. OncoPubMiner makes obtaining precision oncology knowledge from scientific articles straightforward and will assist researchers in efficiently developing structured knowledge base systems and bring us closer to achieving precision oncology goals.
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Neoplasias , Minería de Datos , Humanos , Oncología Médica , Medicina de Precisión , PubMed , PublicacionesRESUMEN
The shape of rice grains not only determines the thousand-grain weight but also correlates closely with the grain quality. Here we identified an ultra-large grain accession (ULG) with a thousand-grain weight exceeding 60 g. The integrated analysis of QTL, BSA, de novo genome assembled, transcription sequencing, and gene editing was conducted to dissect the molecular basis of the ULG formation. The ULG pyramided advantageous alleles from at least four known grain-shaping genes, OsLG3, OsMADS1, GS3, GL3.1, and one novel locus, qULG2-b, which encoded a leucine-rich repeat receptor-like kinase. The collective impacts of OsLG3, OsMADS1, GS3, and GL3.1 on grain size were confirmed in transgenic plants and near-isogenic lines. The transcriptome analysis identified 112 genes cooperatively regulated by these four genes that were prominently involved in photosynthesis and carbon metabolism. By leveraging the pleiotropy of these genes, we enhanced the grain yield, appearance, and stress tolerance of rice var. SN265. Beyond showcasing the pyramiding of multiple grain size regulation genes that can produce ULG, our study provides a theoretical framework and valuable genomic resources for improving rice variety by leveraging the pleiotropy of grain size regulated genes.
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KEY MESSAGE: Our findings highlight a valuable breeding resource, demonstrating the potential to concurrently enhance grain shape, thermotolerance, and alkaline tolerance by manipulating Gγ protein in rice. Temperate Geng/Japonica (GJ) rice yields have improved significantly, bolstering global food security. However, GJ rice breeding faces challenges, including enhancing grain quality, ensuring stable yields at warmer temperatures, and utilizing alkaline land. In this study, we employed CRISPR/Cas9 gene-editing technology to knock out the GS3 locus in seven elite GJ varieties with superior yield performance. Yield component measurements revealed that GS3 knockout mutants consistently enhanced grain length and reduced plant height in diverse genetic backgrounds. The impact of GS3 on the grain number per panicle and setting rate depended on the genetic background. GS3 knockout did not affect milling quality and minimally altered protein and amylose content but notably influenced chalkiness-related traits. GS3 knockout indiscriminately improved heat and alkali stress tolerance in the GJ varieties studied. Transcriptome analysis indicated differential gene expression between the GS3 mutants and their wild-type counterparts, enriched in biological processes related to photosynthesis, photosystem II stabilization, and pathways associated with photosynthesis and cutin, suberine, and wax biosynthesis. Our findings highlight GS3 as a breeding resource for concurrently improving grain shape, thermotolerance, and alkaline tolerance through Gγ protein manipulation in rice.
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Grano Comestible , Oryza , Fitomejoramiento , Proteínas de Plantas , Termotolerancia , Oryza/genética , Oryza/fisiología , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Termotolerancia/genética , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Fenotipo , Edición Génica , Álcalis , Sistemas CRISPR-Cas , Plantas Modificadas Genéticamente/genéticaRESUMEN
BACKGROUND: The 8th AJCC TNM staging for non-metastatic lymph node-positive colon adenocarcinoma patients(NMLP-CA) stages solely by lymph node status, irrespective of the positivity of tumor deposits (TD). This study uses machine learning and Cox regression to predict the prognostic value of tumor deposits in NMLP-CA. METHODS: Patient data from the SEER registry (2010-2019) was used to develop CSS nomograms based on prognostic factors identified via multivariate Cox regression. Model performance was evaluated by c-index, dynamic calibration, and Schmid score. Shapley additive explanations (SHAP) were used to explain the selected models. RESULTS: The study included 16,548 NMLP-CA patients, randomized 7:3 into training (n = 11,584) and test (n = 4964) sets. Multivariate Cox analysis identified TD, age, marital status, primary site, grade, pT stage, and pN stage as prognostic for cancer-specific survival (CSS). In the test set, the gradient boosting machine (GBM) model achieved the best C-index (0.733) for CSS prediction, while the Cox model and GAMBoost model optimized dynamic calibration(6.473) and Schmid score (0.285), respectively. TD ranked among the top 3 most important features in the models, with increasing predictive significance over time. CONCLUSIONS: Positive tumor deposit status confers worse prognosis in NMLP-CA patients. Tumor deposits may confer higher TNM staging. Furthermore, TD could play a more significant role in the staging system.
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Adenocarcinoma , Neoplasias del Colon , Ganglios Linfáticos , Metástasis Linfática , Aprendizaje Automático , Modelos de Riesgos Proporcionales , Humanos , Neoplasias del Colon/patología , Neoplasias del Colon/mortalidad , Masculino , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Femenino , Pronóstico , Persona de Mediana Edad , Ganglios Linfáticos/patología , Anciano , Estadificación de Neoplasias , Nomogramas , Programa de VERFRESUMEN
Electroencephalogram (EEG)-based brain-machine interface (BMI) has the potential to enhance rehabilitation training efficiency, but it still remains elusive regarding how to design BMI training for heterogeneous stroke patients with varied neural reorganization. Here, we hypothesize that tailoring BMI training according to different patterns of neural reorganization can contribute to a personalized rehabilitation trajectory. Thirteen stroke patients were recruited in a 2-week personalized BMI training experiment. Clinical and behavioral measurements, as well as cortical and muscular activities, were assessed before and after training. Following treatment, significant improvements were found in motor function assessment. Three types of brain activation patterns were identified during BMI tasks, namely, bilateral widespread activation, ipsilesional focusing activation, and contralesional recruitment activation. Patients with either ipsilesional dominance or contralesional dominance can achieve recovery through personalized BMI training. Results indicate that personalized BMI training tends to connect the potentially reorganized brain areas with event-contingent proprioceptive feedback. It can also be inferred that personalization plays an important role in establishing the sensorimotor loop in BMI training. With further understanding of neural rehabilitation mechanisms, personalized treatment strategy is a promising way to improve the rehabilitation efficacy and promote the clinical use of rehabilitation robots and other neurotechnologies.
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Interfaces Cerebro-Computador , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Medicina de Precisión , Accidente Cerebrovascular/terapia , EncéfaloRESUMEN
Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H2O2) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO2@Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO2) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H2O2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO2@Dex into biofilms, while CaO2 generated a substantial amount of H2O2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H2O2 into hydroxyl radicals (â¢OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO2@Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.
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Infecciones Bacterianas , Staphylococcus aureus Resistente a Meticilina , Neoplasias , Humanos , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno , Antibacterianos/farmacología , Biopelículas , Glutatión , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Temperate japonica/geng (GJ) rice yield has significantly improved due to intensive breeding efforts, dramatically enhancing global food security. However, little is known about the underlying genomic structural variations (SVs) responsible for this improvement. We compared 58 long-read assemblies comprising cultivated and wild rice species in the present study, revealing 156 319 SVs. The phylogenomic analysis based on the SV dataset detected the putatively selected region of GJ sub-populations. A significant portion of the detected SVs overlapped with genic regions were found to influence the expression of involved genes inside GJ assemblies. Integrating the SVs and causal genetic variants underlying agronomic traits into the analysis enables the precise identification of breeding signatures resulting from complex breeding histories aimed at stress tolerance, yield potential and quality improvement. Further, the results demonstrated genomic and genetic evidence that the SV in the promoter of LTG1 is accounting for chilling sensitivity, and the increased copy numbers of GNP1 were associated with positive effects on grain number. In summary, the current study provides genomic resources for retracing the properties of SVs-shaped agronomic traits during previous breeding procedures, which will assist future genetic, genomic and breeding research on rice.
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Oryza , Oryza/genética , Fitomejoramiento , Genómica/métodos , Fenotipo , Grano ComestibleRESUMEN
Proper cell fate determination is largely orchestrated by complex gene regulatory networks centered around transcription factors. However, experimental elucidation of key transcription factors that drive cellular identity is currently often intractable. Here, we present ANANSE (ANalysis Algorithm for Networks Specified by Enhancers), a network-based method that exploits enhancer-encoded regulatory information to identify the key transcription factors in cell fate determination. As cell type-specific transcription factors predominantly bind to enhancers, we use regulatory networks based on enhancer properties to prioritize transcription factors. First, we predict genome-wide binding profiles of transcription factors in various cell types using enhancer activity and transcription factor binding motifs. Subsequently, applying these inferred binding profiles, we construct cell type-specific gene regulatory networks, and then predict key transcription factors controlling cell fate transitions using differential networks between cell types. This method outperforms existing approaches in correctly predicting major transcription factors previously identified to be sufficient for trans-differentiation. Finally, we apply ANANSE to define an atlas of key transcription factors in 18 normal human tissues. In conclusion, we present a ready-to-implement computational tool for efficient prediction of transcription factors in cell fate determination and to study transcription factor-mediated regulatory mechanisms. ANANSE is freely available at https://github.com/vanheeringen-lab/ANANSE.
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Algoritmos , Biología Computacional/métodos , Elementos de Facilitación Genéticos/genética , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Factores de Transcripción/genética , Diferenciación Celular/genética , Secuenciación de Inmunoprecipitación de Cromatina , Células Epiteliales/citología , Células Epiteliales/metabolismo , Humanos , Especificidad de Órganos/genética , RNA-Seq/métodos , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Sensory stimulation can play a fundamental role in the activation of the primary sensorimotor cortex (S1-M1), which can promote motor learning and M1 plasticity in stroke patients. However, studies have focused mainly on investigating the influence of brain lesion profiles on the activation patterns of S1-M1 during motor tasks instead of sensory tasks. Therefore, the objective of this study is to explore the lesion-specific activation patterns due to different brain lesion profiles and types during focal vibration (FV). METHODS: In total 52 subacute stroke patients were recruited in this clinical experiment, including patients with basal ganglia hemorrhage/ischemia, brainstem ischemia, other subcortical ischemia, cortical ischemia, and mixed cortical-subcortical ischemia. Electroencephalograms (EEG) were recorded following a resting state lasting for 4 min and three sessions of FV. FV was applied over the muscle belly of the affected limb's biceps for 3 min each session. Beta motor-related EEG power desynchronization overlying S1-M1 was used to indicate the activation of S1-M1, while the laterality coefficient (LC) of the activation of S1-M1 was used to assess the interhemispheric asymmetry of brain activation. RESULTS: (1) Regarding brain lesion profiles, FV could lead to the significant activation of bilateral S1-M1 in patients with basal ganglia ischemia and other subcortical ischemia. The activation of ipsilesional S1-M1 in patients with brainstem ischemia was higher than that in patients with cortical ischemia. No activation of S1-M1 was observed in patients with lesions involving cortical regions. (2) Regarding brain lesion types, FV could induce the activation of bilateral S1-M1 in patients with basal ganglia hemorrhage, which was significantly higher than that in patients with basal ganglia ischemia. Additionally, LC showed no significant correlation with the modified Barthel index (MBI) in all patients, but a positive correlation with MBI in patients with basal ganglia lesions. CONCLUSIONS: These results reveal that sensory stimulation can induce lesion-specific activation patterns of S1-M1. This indicates FV could be applied in a personalized manner based on the lesion-specific activation of S1-M1 in stroke patients with different lesion profiles and types. Our study may contribute to a better understanding of the underlying mechanisms of cortical reorganization.
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Hemorragia de los Ganglios Basales , Accidente Cerebrovascular , Humanos , Encéfalo , Electroencefalografía , Isquemia , Imagen por Resonancia MagnéticaRESUMEN
A periodic intermittent adaptive control method with saturation is proposed to pin the quasi-consensus of nonlinear heterogeneous multi-agent systems with external disturbances in this paper. A new periodic intermittent adaptive control protocol with saturation is designed to control the internal coupling between the follower agents and the feedback gain between the leader and the follower. In particular, we use the saturation adaptive law: when the quasi-consensus error converges to a certain range, the adaptive coupling edge weight and the adaptive feedback gain will not be updated. Furthermore, we propose three saturated adaptive pinning control protocols. The quasi-consensus is achieved through its own pinning as long as the agents remain connected to each other. Using the Lyapunov function method and inequality technique, the convergence range of the quasi-consensus error of a heterogeneous multi-agent system is obtained. Finally, the rationality of the proposed control protocol is verified through numerical simulation. Theoretical derivation and simulation results show that the novel proposed periodic intermittent adaptive control method with saturation can successfully be used to achieve the pinning of quasi-consensus of nonlinear heterogeneous multi-agent systems.
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Ether solvents with superior reductive stability promise excellent interphasial stability with high-capacity anodes while the limited oxidative resistance hinders their high-voltage operation. Extending the intrinsic electrochemical stability of ether-based electrolytes to construct stable-cycling high-energy-density lithium-ion batteries is challenging but rewarding. Herein, the anion-solvent interactions were concerned as the key point to optimize the anodic stability of the ether-based electrolytes and an optimized interphase was realized on both pure-SiOx anodes and LiNi0.8 Mn0.1 Co0.1 O2 cathodes. Specifically, the small-anion-size LiNO3 and tetrahydrofuran with high dipole moment to dielectric constant ratio realized strengthened anion-solvent interactions, which enhance the oxidative stability of the electrolyte. The designed ether-based electrolyte enabled a stable cycling performance over 500â cycles in pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 full cell, demonstrating its superior practical prospects. This work provides new insight into the design of new electrolytes for emerging high-energy density lithium-ion batteries through the regulation of interactions between species in electrolytes.
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Cell walls constitute the majority of plant biomass and are essential for plant resistance to environmental stresses. It is promising to improve both plant biomass production and stress resistance simultaneously by genetic modification of cell walls. Here, we report the functions of a UDP-galactose/glucose epimerase 3 (OsUGE3) in rice growth and salt tolerance by characterizing its overexpressing plants (OsUGE3-OX) and loss-of-function mutants (uge3). The OsUGE3-OX plants showed improvements in biomass production and mechanical strength, whereas uge3 mutants displayed growth defects. The OsUGE3 exhibits UDP-galactose/glucose epimerase activity that provides substrates for polysaccharides polymerization, consistent with the increased biosynthesis of cellulose and hemicelluloses and strengthened walls in OsUGE3-OX plants. Notably, the OsUGE3 is ubiquitously expressed and induced by salt treatment. The uge3 mutants were hypersensitive to salt and osmotic stresses, whereas the OsUGE3-OX plants showed improved tolerance to salt and osmotic stresses. Moreover, OsUGE3 overexpression improves the homeostasis of Na+ and K+ and induces a higher accumulation of hemicelluloses and soluble sugars during salt stress. Our results suggest that OsUGE3 improves biomass production, mechanical strength, and salt stress tolerance by reinforcement of cell walls with polysaccharides and it could be targeted for genetic modification to improve rice growth under salt stress.
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Oryza , Tolerancia a la Sal , Biomasa , Pared Celular/metabolismo , Galactosa , Regulación de la Expresión Génica de las Plantas , Glucosa , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Polisacáridos , Racemasas y Epimerasas/genética , Tolerancia a la Sal/genética , Estrés Fisiológico/genética , Uridina DifosfatoRESUMEN
Moiré configurations have recently attracted much attention due to their ability to enhance photonic responses and manipulate surface waves in the subwavelength ranges. However, previous studies have usually been focused on natural hyperbolic materials with limitations on patterning procedures, controlling rotation angles, and merely manipulating electric surface plasmons. Here, we theoretically and numerically investigate a novel magnetic moiré hyperbolic metasurface in the terahertz region, which enables two types of topological transition and a plethora of unusual magnetic moiré effects (magnetic surface wave manipulation, dispersion engineering, magic angles, spacer-dependent topological transition, and local field enhancement). This work extends twistronics and moiré physics to the terahertz region and magnetic polaritons, with potential applications in quantum physics, energy transfer, and planarized magnetic plasmonic devices.
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Bound state in the continuum (BIC) refers to the trapped state in the radiation continuum of a system. In the terahertz band, BIC provides a unique and feasible method to design devices with ultra-high quality factor (Q factor) and to achieve intense terahertz-matter interaction, which is of great value to terahertz science and technology. Here, multiple BICs protected by the resonance symmetry in the terahertz metasurface consisting of metallic split ring resonators (SRR) is demonstrated. The evolution from the BIC to the quasi-BIC (QBIC) is induced by changing the gap width of the SRRs. The proposed BICs are experimentally demonstrated and analyzed by the coupled mode theory along with the numerical simulation. It is found that the leakage behavior of these QBICs is strongly affected by the intrinsic Ohmic loss in the SRRs while it is quite robust to the tilted incidence.
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Various kinds of metasurfaces have been proposed because they can be tailored to achieve the desired modulations on electromagnetic wave that do not occur in nature. Compared to conventional metamaterials, coding metasurfaces integrated with information science theory possess numerous distinctive advantages - simple design, time-saving and compatibility with digital devices. Here we propose terahertz multifunctional anisotropic reflective metasurfaces with a metal-insulator-metal cavity structure whose top constructional layer consists of a pair of gold arc-rings and a gold cut-wire located between them. Two different functions of narrow-band absorption and broadband polarization conversion are realized based on different coding matrices using the binary codes '0' and '1'. Furthermore, we integrate a specific coding metasurface with vanadium dioxide (VO2) to realize a temperature-controlled active metasurface. Through the temperature change, dynamic functionalities switching between a narrow-band polarization converter with a polarization conversion ratio over 94% and an efficient low-pass filter are achieved under the phase transition of VO2, and the active metasurface is polarization independent. The proposed coding metasurfaces are verified numerically and experimentally, and have promising applications in terahertz modulation and functional devices.
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Although UDP-glucuronic acid decarboxylases (UXSs) have been well studied with regard to catalysing the conversion of UDP-glucuronic acid into UDP-xylose, their biological roles in grasses remain largely unknown. The rice (Oryza sativa) genome contains six UXSs, but none of them has been genetically characterized. Here, we reported on the characterization of a novel rice fragile culm mutant, fc18, which exhibited brittleness with altered cell wall and pleiotropic defects in growth. Map-based cloning and transgenic analyses revealed that the FC18 gene encodes a cytosol-localized OsUXS3 and is widely expressed with higher expression in xylan-rich tissues. Monosaccharide analysis showed that the xylose level was decreased in fc18, and cell wall fraction determinations confirmed that the xylan content in fc18 was lower, suggesting that UDP-xylose from FC18 participates in xylan biosynthesis. Moreover, the fc18 mutant displayed defective cellulose properties, which led to an enhancement in biomass saccharification. Furthermore, expression of genes involved in sugar metabolism and phytohormone signal transduction was largely altered in fc18. Consistent with this, the fc18 mutant exhibited significantly reduced free auxin (indole-3-acetic acid) content and lower expression levels of PIN family genes compared with wild type. Our work reveals the physiological roles of FC18/UXS3 in xylan biosynthesis, cellulose deposition, and plant growth in rice.
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Carboxiliasas , Oryza , Carboxiliasas/genética , Carboxiliasas/metabolismo , Pared Celular/metabolismo , Celulosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácido Glucurónico/metabolismo , Oryza/metabolismo , Uridina Difosfato Xilosa/metabolismo , Xilanos , Xilosa/metabolismoRESUMEN
BACKGROUND: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. METHODS: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. RESULTS: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non-immunosuppression and immunosuppression groups, respectively. Relative to non-immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable-adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18-0.40; p < 0.001) and IPTW-weighted Cox model (HR 0.28; 95% CI 0.19-0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1-month increase; 95% CI 0.87-0.92; p < 0.001; IPTW-adjusted). Combination therapy with steroids and non-steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07-0.26; p < 0.001). CONCLUSION: Immunosuppression significantly reduced the 2-year risk of generalization in patients with OMG.