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Recent progress in metagratings highlights the promise of high-performance wavefront engineering devices, notably for their exterior capability to steer beams with near-unitary efficiency. However, the narrow operating bandwidth of conventional metagratings remains a significant limitation. Here, we propose and experimentally demonstrate a dual-layer metagrating, incorporating enhanced interlayer couplings to realize high-efficiency and broadband anomalous reflection within the microwave frequency band. The metagrating facilitated by both intralayer and interlayer couplings is designed through the combination of eigenmode expansion (EME) algorithm and particle swarm optimization (PSO) to significantly streamline the computational process. Our metagrating demonstrates the capacity to reroute a normally incident wave to +1 order diffraction direction across a broad spectrum, achieving an average efficiency approximately 90% within the 14.7 to 18â GHz range. This study may pave the way for future applications in sophisticated beam manipulations, including spatial dispersive devices, by harnessing the intricate dynamics of multi-layer metagratings with complex interlayer and intralayer interactions.
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BACKGROUND & AIMS: Early recurrence of hepatocellular carcinoma (HCC) after curative resection is common. However, the association between genetic mechanisms and early HCC recurrence, especially in Chinese patients, remains largely unknown. METHODS: We performed whole-genome sequencing (49 cases), whole-exome sequencing (18 cases), and deep targeted sequencing (115 cases) on 182 primary HCC samples. Focusing on WNK2, we used Sanger sequencing and qPCR to evaluate all the coding exons and copy numbers of that gene in an additional 554 HCC samples. We also explored the functional effect and mechanism of WNK2 on tumor growth and metastasis. RESULTS: We identified 5 genes (WNK2, RUNX1T1, CTNNB1, TSC1, and TP53) harboring somatic mutations that correlated with early tumor recurrence after curative resection in 182 primary HCC samples. Focusing on WNK2, the overall somatic mutation and copy number loss occurred in 5.3% (39/736) and 27.2% (200/736), respectively, of the total 736 HCC samples. Both types of variation were associated with lower WNK2 protein levels, higher rates of early tumor recurrence, and shorter overall survival. Biofunctional investigations revealed a tumor-suppressor role of WNK2: its inactivation led to ERK1/2 signaling activation in HCC cells, tumor-associated macrophage infiltration, and tumor growth and metastasis. CONCLUSIONS: Our results delineate genomic events that characterize Chinese HCCs and identify WNK2 as a driver of early HCC recurrence after curative resection. LAY SUMMARY: We applied next-generation sequencing and conducted an in-depth genomic analysis of hepatocellular carcinomas from a Chinese patient cohort. The results delineate the genomic events that characterize hepatocellular carcinomas in Chinese patients and identify WNK2 as a driver associated with early tumor recurrence after curative resection.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Recidiva Local de Neoplasia/genética , Proteínas Serina-Treonina Quinases/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , China , Feminino , Genes Supressores de Tumor , Predisposição Genética para Doença , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/patologia , Proteína 1 Parceira de Translocação de RUNX1/genética , Transdução de Sinais , Sequenciamento do Exoma , beta Catenina/genéticaRESUMO
Asian cultivated rice consists of two subspecies: Oryza sativa subsp. indica and O. sativa subsp. japonica Despite the fact that indica rice accounts for over 70% of total rice production worldwide and is genetically much more diverse, a high-quality reference genome for indica rice has yet to be published. We conducted map-based sequencing of two indica rice lines, Zhenshan 97 (ZS97) and Minghui 63 (MH63), which represent the two major varietal groups of the indica subspecies and are the parents of an elite Chinese hybrid. The genome sequences were assembled into 237 (ZS97) and 181 (MH63) contigs, with an accuracy >99.99%, and covered 90.6% and 93.2% of their estimated genome sizes. Comparative analyses of these two indica genomes uncovered surprising structural differences, especially with respect to inversions, translocations, presence/absence variations, and segmental duplications. Approximately 42% of nontransposable element related genes were identical between the two genomes. Transcriptome analysis of three tissues showed that 1,059-2,217 more genes were expressed in the hybrid than in the parents and that the expressed genes in the hybrid were much more diverse due to their divergence between the parental genomes. The public availability of two high-quality reference genomes for the indica subspecies of rice will have large-ranging implications for plant biology and crop genetic improvement.
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Cromossomos de Plantas/genética , Variação Genética , Genoma de Planta/genética , Oryza/genética , Mapeamento Cromossômico/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Mutação INDEL , Oryza/classificação , Polimorfismo de Nucleotídeo Único , Especificidade da EspécieRESUMO
The first total synthesis of mycoleptodiscinâ A, a structurally unusual indolosesquiterpenoid possessing an ortho-benzoquinone motif, has been accomplished. A sulfone alkylation coupled two readily available fragments to give an aryl triene intermediate. The tetracyclic core of the molecule was assembled through a highly enantioselective iridium-catalyzed polyene cyclization. The benzylic homologation was achieved by a cationic cyanation. The indole motif was constructed via a copper-mediated intramolecular C-N bond formation at a late stage.
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Alcaloides/síntese química , Alcaloides/química , Ciclização , Modelos Moleculares , Estrutura MolecularRESUMO
Owing to the inherent advantages of parallelism, rapid processing speed, and minimal energy consumption, optical analog computing has witnessed a progressive development. Quantum optical computing exceeds the capabilities of classical computing in terms of computational speed in numerous tasks. However, existing metamaterial-based quantum Deutsch-Jozsa (DJ) algorithm devices have large structural dimensions and are not suitable for miniaturized optical computing systems. Furthermore, most reported on-chip metasurface devices, rendered monofunctional after fabrication, do not possess sophisticated optical systems. In this work, we develop an electrically tunable on-chip DJ algorithm device on a lithium-niobate-on-insulator (LNOI) platform. The on-chip device consists of various etched slots, each with carefully designed size. By applying different external voltages to each individual unit, precise phase redistribution across the device is attainable, enabling the realization of tunable DJ algorithm. Notably, we can determine whether the oracle metasurface yields a constant or balance function by measuring the output electric field. The on-chip device is miniaturized and easy to integrate while enabling functional reconfiguration, which paves the way for numerous applications in optical computing.
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Organic-inorganic hybrid perovskite (OIHP) has attracted a great deal of interest with respect to diverse optoelectronic devices. However, the photophysical properties of the OIHP require further understanding because most of the investigations have been conducted with polycrystalline perovskites, which contain high-density structural defects. Here, diverse photophysical properties, including structural characterization, spectroscopic features, and photoexcited products, are studied in submicrometer CH3NH3PbBr3 ultrathin single-crystal (UTSC) films. Unlike polycrystalline films and large single crystals, the UTSC film provides a unique platform for studying spectroscopic characteristics of single-crystal perovskites. Compared with the polycrystalline film, the UTSC film presents an atomically flat morphology and near-perfect lattice with a lower defect density, leading to an isotropic system that can be applied in the construction of high-performance optoelectronic devices. Furthermore, a long lifetime emissive channel assigned to the trion is indicated, which is scarcely found in perovskite polycrystalline films. Our results profoundly improve our understanding of their photophysical properties and expand the horizons for perovskite materials in photonic applications.
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Fibroins' transition from liquid to solid is fundamental to spinning and underpins the impressive native properties of silk. Herein, we establish a fibroin heavy chain fold for the Silk-I polymorph, which could be relevant for other similar proteins, and explains mechanistically the liquid-to-solid transition of this silk, driven by pH reduction and flow stress. Combining spectroscopy and modelling we propose that the liquid Silk-I fibroin heavy chain (FibH) from the silkworm, Bombyx mori, adopts a newly reported ß-solenoid structure. Similarly, using rheology we propose that FibH N-terminal domain (NTD) templates reversible higher-order oligomerization driven by pH reduction. Our integrated approach bridges the gap in understanding FibH structure and provides insight into the spatial and temporal hierarchical self-assembly across length scales. Our findings elucidate the complex rheological behaviour of Silk-I, solutions and gels, and the observed liquid crystalline textures within the silk gland. We also find that the NTD undergoes hydrolysis during standard regeneration, explaining key differences between native and regenerated silk feedstocks. In general, in this study we emphasize the unique characteristics of native and native-like silks, offering a fresh perspective on our fundamental understanding of silk-fibre production and applications.
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Bombyx , Fibroínas , Bombyx/metabolismo , Bombyx/química , Animais , Fibroínas/química , Fibroínas/metabolismo , Reologia , Seda/química , Seda/metabolismo , Concentração de Íons de HidrogênioRESUMO
Patients with hepatocellular carcinoma (HCC) have poor long-term survival following curative resection because of the high rate of tumor early recurrence. Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC. In this study, we performed whole-genome sequencing (WGS) on 40 pairs of primary and early-recurrent hepatitis B virus (HBV)-related HCC tumors from patients who received curative resection, and from four patients whose primary and recurrent tumor were extensively sampled. We identified two recurrence patterns: de novo recurrence (18/40), which developed genetically independently of the primary tumor and carried different HCC drivers, and ancestral recurrence (22/40), which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence. We found that the recurrence location was predictive of the recurrence pattern: distant recurrence tended to display the de novo pattern, whereas local recurrence tended to display the ancestral pattern. We then uncovered the evolutionary trajectories based on the subclonal architecture, driver-gene mutations, and mutational processes observed in the primary and recurrent tumors. Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal, monophyletic dissemination in HCC ancestral recurrence. In addition, we identified recurrence-specific mutations and copy-number gains in BCL9, leading to WNT/ß-catenin signaling activation and an immune-excluded tumor microenvironment, which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC. Collectively, our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence, providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.
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Carcinoma Hepatocelular/genética , Vírus da Hepatite B/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Via de Sinalização Wnt/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Proteínas de Neoplasias/metabolismo , Sequenciamento Completo do GenomaRESUMO
Two new selaginellin derivatives, selaginellins K (1) and L (2), were isolated from Selaginella tamariscina (Beauv.) Spring and characterized as 2-formyl-4,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene and 4,4'-dihydroxy-2-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene on the basis of their spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS spectroscopic analysis.
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Compostos de Bifenilo/isolamento & purificação , Cicloexanonas/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Selaginellaceae/química , Compostos de Bifenilo/química , Cicloexanonas/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EOs) are important active ingredients in Chinese herbal medicine. Cymbopogon citratus (DC.) Stapf, Cinnamomum cassia (L.) Presl, Salvia japonica Thunb., and Rosa rugosa Thunb. are used in local and traditional medicine to treat inflammation-related diseases. While the constituents and bioactivities of EOs of the above four Chinese herbals have been reported previously, but their anti-inflammatory and antioxidant activities have not been systematically evaluated. AIM OF THE STUDY: The purpose of this study was to research the chemical constituents, anti-inflammatory activities, and antioxidant activities of EOs of four Chinese herbal medicines. MATERIALS AND METHODS: Fresh plant materials were collected both in August 2018. The compositions of EOs were determined by the gas chromatography-mass spectrometry (GC-MS) method. TPA (12-O-tetradecylphophenol-13-acetate)-induced mouse ear model was evaluated the anti-inflammatory activities of EOs. The reduction of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and RelA protein of the nuclear factor kappa-B (NF-κB) in the signal pathway (P65) were measured. The antioxidant activities of EOs from four plants were determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. RESULTS: A total of 217 compounds were separated and identified from four EOs, mainly including trans-cinnamylaldehyde (68.75%), citronellal (38.16%), linalool (1.02-33.73%), geraniol (19.39%) and citronellol (17.18%). All four EOs reduced the damage of the ear tissue and had certain anti-inflammatory effects, and the EOs of C. citratus (CyCEOs) and S. japonica (SJEOs) had the best anti-inflammatory activities among others, even better than ibuprofen. The four EOs exhibited different DPPH radical-scavenging activities (IC50, 0.101-1.017%), where most of them were much lower than that of EOs of C. citratus (CiCEOs) (IC50, 0.101%) and EOs of R. rugosa (RREOs) (IC50, 0.142%). CONCLUSIONS: The main components determine diverse propertise of these four EOs, our results suggested that four EOs presented anti-inflammatory and antioxidant effect via reducing the expression of TNF-a, IL-6, COX-2, and NF-κB p65, which may provide a new approach for development of new anti-inflammatory drugs.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/química , Óleos Voláteis/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Modelos Animais de Doenças , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificaçãoRESUMO
Ultrasonic probe-assisted enzymolysis technology was developed to improve the hydrolysis efficiency of soy sauce residue (SSR). The effects of enzyme type and enzymatic hydrolysis parameters on the hydrolysis degree of SSR were studied firstly to obtain the optimal enzymatic hydrolysis conditions. Then the effects of ultrasound on protease activity and structure of SSR were investigated to elucidate the acting mechanism of ultrasound. Finally, the ultrasonic-assisted enzymatic hydrolysis modes were designed and compared, and the hydrolysates from SSR were characterized to evaluate their further application. The results showed that a hydrolysis degree of 15.53% could be obtained under the optimum enzymolysis conditions: enzyme amount 6000U/g, pH 7.8, temperature 50°C, the ratio of substrate to water phase 1:20, hydrolysis time 4h. Increasing ultrasound treatment time or power could reduce substrate size and consequently enhance the catalytic surface area. Prolonging ultrasound treatment time had a negative influence on enzyme activity, but low ultrasound power was helpful for increasing the enzyme activity. Ultrasound pretreatment of SSR followed by enzymatic hydrolysis increased the hydrolysis degree by 47.6%. When the ultrasound was applied directly to enzymolysis process, the hydrolysis degree of SSR exhibited an increase of 33.0%. The hydrolysates from SSR exhibited good antioxidant activities, and had a potential use as a functional ingredient in food or feed industry.
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Biotecnologia/métodos , Peptídeo Hidrolases/metabolismo , Alimentos de Soja , Ondas Ultrassônicas , Hidrólise , CinéticaRESUMO
Over the past 30 years, we have performed many fundamental studies on two Oryza sativa subsp. indica varieties, Zhenshan 97 (ZS97) and Minghui 63 (MH63). To improve the resolution of many of these investigations, we generated two reference-quality reference genome assemblies using the most advanced sequencing technologies. Using PacBio SMRT technology, we produced over 108 (ZS97) and 174 (MH63) Gb of raw sequence data from 166 (ZS97) and 209 (MH63) pools of BAC clones, and generated ~97 (ZS97) and ~74 (MH63) Gb of paired-end whole-genome shotgun (WGS) sequence data with Illumina sequencing technology. With these data, we successfully assembled two platinum standard reference genomes that have been publicly released. Here we provide the full sets of raw data used to generate these two reference genome assemblies. These data sets can be used to test new programs for better genome assembly and annotation, aid in the discovery of new insights into genome structure, function, and evolution, and help to provide essential support to biological research in general.
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Genoma , Oryza/genéticaRESUMO
A divergent approach was developed toward the total synthesis of taiwaniaquinoids. An advanced intermediate 5a with trans A/B ring junction was concisely assembled by employing a Bi(OTf)3-catalyzed cationic cyclization and a Wolff-type ring contraction as key steps. This common intermediate was readily converted to racemic taiwaniaquinones A and F and taiwaniaquinols B and D, respectively.