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SignificanceThe quantum-mechanical geometric phase of electrons provides various phenomena such as the dissipationless photocurrent generation through the shift current mechanism. So far, the photocurrent generations are limited to above or near the band-gap photon energy, which contradicts the increasing demand of the low-energy photonic functionality. We demonstrate the photocurrent through the optical phonon excitations in ferroelectric BaTiO3 by using the terahertz light with photon energy far below the band gap. This photocurrent without electron-hole pair generation is never explained by the semiclassical treatment of electrons and only arises from the quantum-mechanical geometric phase. The observed photon-to-current conversion efficiency is as large as that for electronic excitation, which can be well accounted for by newly developed theoretical formulation of shift current.
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GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.
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ADN Helicasas , ARN Helicasas , Humanos , Proteínas de Unión a Poli-ADP-Ribosa , Proteínas con Motivos de Reconocimiento de ARN , Regiones no Traducidas 5' , Cuerpos de Inclusión Intranucleares , Ribosomas , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
Oral squamous cell carcinoma (OSCC) is a malignant neoplasm with high mortality and morbidity. The role of circRNA and its molecular mechanism in OSCC remains largely unknown. The study aims to explore the role of a novel circular RNA (circLDLRAD3) in OSCC and its underlying mechanism. PCR and fluorescence in situ hybridization were used to explore the expression features of circLDLRAD3 in OSCC. The effects of circLDLRAD3 on the behaviour of OSCC were investigated using CCK-8, colony formation assay, transwell and animal experiments. Bioinformatics analysis along with dual luciferase reporter assay and RIP assay were used to reveal the interaction between circLDLRAD3, miR-558 and Smad4. It was revealed that circLDLRAD3 exhibited low expression status in OSCC. CircLDLRAD3 inhibits proliferation, migration, and invasion of OSCC cells both in vitro and in vivo. Mechanistically, circLDLRAD3 could bind with miR-558 to positively regulate its target gene Smad4 expression. Rescue experiments further confirmed both miR-558 overexpression and Smad4 knockdown could reverse the influence of circLDLRAD3 on OSCC phenotypes. Moreover, circLDLRAD3 regulate the TGF-ß signalling pathways to influence EMT through miR-558/Smad4 axis. Our study found that circLDLRAD3 is downregulated in OSCC and verified its tumour suppressor function and mechanism in OSCC through sponging miR-558 to regulate miR-558/Smad4/TGF-ß axis. The characterization of such regulating network uncovers an important mechanism underlying OSCC progression, which could provide promising targets targeted therapy strategies for OSCC in the future.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Animales , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , MicroARNs/genética , MicroARNs/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Hibridación Fluorescente in Situ , Línea Celular Tumoral , Neoplasias de la Boca/patología , ARN Circular/genética , Neoplasias de Cabeza y Cuello/genética , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) are three nervous system diseases that partially overlap clinically and genetically. However, bulk RNA-sequencing did not accurately detect the core pathogenic molecules in them. The availability of high-quality single cell RNA-sequencing data of post-mortem brain collections permits the generation of a large-scale gene expression in different cells in human brain, focusing on the molecular features and relationships between diseases and genes. We integrated single-nucleus RNA-sequencing (snRNA-seq) datasets of human brains with AD, PD, and MS to identify transcriptomic commonalities and distinctions among them. METHODS: The snRNA-seq datasets were downloaded from Gene Expression Omnibus (GEO) database. The Seurat package was used for snRNA-seq data processing. The uniform manifold approximation and projection (UMAP) were utilized for cluster identification. The FindMarker function in Seurat was used to identify the differently expressed genes. Functional enrichment analysis was carried out using the Gene Set Enrichment Analysis (GSEA) and Gene ontology (GO). The protein-protein interaction (PPI) analysis of differentially expressed genes (DEGs) was analyzed using STRING database ( http://string-db.org ). SCENIC analysis was performed using utilizing pySCENIC (v0.10.0) based on the hg19-tss-centered-10 kb-10species databases. The analysis of potential therapeutic drugs was analyzed on Connectivity Map ( https://clue.io ). RESULTS: The gene regulatory network analysis identified several hub genes regulated in AD, PD, and MS, in which HSPB1 and HSPA1A were key molecules. These upregulated HSP family genes interact with ribosome genes in AD and MS, and with immunomodulatory genes in PD. We further identified several transcriptional regulators (SPI1, CEBPA, TFE3, GRHPR, and TP53) of the hub genes, which has important implications for uncovering the molecular crosstalk among AD, PD, and MS. Arctigenin was identified as a potential therapeutic drug for AD, PD, and MS. CONCLUSIONS: Together, the integrated snRNA-seq data and findings have significant implications for unraveling the shared and unique molecular crosstalk among AD, PD, and MS. HSPB1 and HSPA1A as promising targets involved in the pathological mechanisms of neurodegenerative diseases. Additionally, the identification of arctigenin as a potential therapeutic drug for AD, PD, and MS further highlights its potential in treating these neurological disorders. These discoveries lay the groundwork for future research and interventions to enhance our understanding and treatment of AD, PD, and MS.
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Enfermedad de Alzheimer , Esclerosis Múltiple , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Esclerosis Múltiple/genética , Enfermedad de Alzheimer/genética , ARNRESUMEN
We propose a time-reversal-even spin generation in second order of electric fields, which dominates the current induced spin polarization in a wide class of centrosymmetric nonmagnetic materials, and leads to a novel nonlinear spin-orbit torque in magnets. We reveal a quantum origin of this effect from the momentum space dipole of the anomalous spin polarizability. First-principles calculations predict sizable spin generations in several nonmagnetic hcp metals, in monolayer TiTe_{2}, and in ferromagnetic monolayer MnSe_{2}, which can be detected in experiment. Our work opens up the broad vista of nonlinear spintronics in both nonmagnetic and magnetic systems.
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The simulation of fermionic relativistic physics, e.g., Dirac and Weyl physics, has led to the discovery of many unprecedented phenomena in photonics, of which the optical-frequency realization is, however, still challenging. Here, surprisingly, we discover that the woodpile photonic crystals commonly used for optical frequency applications host exotic fermion-like relativistic degeneracies: a Dirac nodal line and a fourfold quadratic point, as protected by the nonsymmorphic crystalline symmetry. Deforming the woodpile photonic crystal leads to the emergence of type-II Dirac points from the fourfold quadratic point. Such type-II Dirac points can be detected by its anomalous refraction property which is manifested as a giant birefringence in a slab setup. Our findings provide a promising route towards 3D optical Dirac physics in all-dielectric photonic crystals.
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Resulting from strong magnetic anisotropy two-dimensional ferromagnetism was recently shown to be stabilized in chromium triiodide, CrI3, in the monolayer limit. While its properties remain largely unexplored, it provides a unique material-specific platform to unveil its electromagnetic properties associated with coupling of modes. Indeed, trigonal symmetry in the presence of out-of-plane magnetization results in a non-trivial structure of the conductivity tensor, including the off-diagonal terms. In this paper, we study the surface electromagnetic waves localized in a CrI3-based structure using the results of ab initio calculations for the CrI3 conductivity tensor. In particular, we provide an estimate for the critical angle corresponding to the surface plasmon polariton generation in the Kretschmann-Raether configuration by a detailed investigation of reflectance spectrum as well as the magnetic field distribution for different CrI3 layer thicknesses. We also study the bilayer structure formed by two CrI3 layers separated by a SiO2 spacer and show that the surface plasmon resonance can be achieved at the interface between CrI3 and air depending on the spacer thickness.
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Higher-order topology yields intriguing multidimensional topological phenomena, while Weyl semimetals have unconventional properties such as chiral anomaly. However, so far, Weyl physics remain disconnected with higher-order topology. Here, we report the theoretical discovery of higher-order Weyl semimetals and thereby the establishment of such an important connection. We demonstrate that higher-order Weyl semimetals can emerge in chiral materials such as chiral tetragonal crystals as the intermediate phase between the conventional Weyl semimetal and 3D higher-order topological phases. Higher-order Weyl semimetals manifest themselves uniquely by exhibiting concurrent chiral Fermi-arc surface states, topological hinge states, and the momentum-dependent fractional hinge charge, revealing a novel class of higher-order topological phases.
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BACKGROUND: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. METHODS: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. RESULTS: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = - 1.44, 95% CI = (- 1.68,- 1.19)] and acute migraine-specific medication days [WMD = - 1.28, 95% CI = (- 1.66,- 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. CONCLUSIONS: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.
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Anticuerpos Monoclonales/administración & dosificación , Péptido Relacionado con Gen de Calcitonina/inmunología , Trastornos Migrañosos/prevención & control , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
We report crystal growth, AC and DC magnetic susceptibilities [χ(T, H)], magnetization [M(T, H)], and heat capacity [CP(T, H)] measurement results of GdSbTe single crystal. GdSbTe is isostructural to the confirmed nonmagnetic nodal-line semimetal ZrSiS of noncentrosymmetric tetragonal crystal structure in space group P4/nmm (No. 129), but it shows additional long-range antiferromagnetic spin ordering for the Gd spins of S = 7/2 below TN. Both χ(T, H) and CP(T, H) measurements confirm the existence of a long-range antiferromagnetic (AFM) spin ordering of Gd spins below TN â¼ 12 K, and an additional spin reorientation/recovery (sr) behavior is identified from the change of on-site spin anisotropy between Tsr1 â¼ 7 and Tsr2 â¼ 4 K. The anisotropic magnetic susceptibilities of χ(T, H) below TN clearly demonstrate that the AFM long-range spin ordering of GdSbTe has an easy axis parallel to the ab-plane direction. The field- and orientation-dependent magnetization of M(T, H) at 2 K shows two plateaus to indicate the spin-flop transition for H||ab near â¼2.1 T and a metamagnetic state near â¼5.9 T having â¼1/3 of the fully polarized magnetization by the applied field. The heat capacity measurement results yield Sommerfeld coefficient of γ â¼ 7.6(4) mJ/mol K2 and θD â¼ 195(2) K being less than half of that for the nonmagnetic ZrSiS. A three-dimensional (3D) AFM spin structure is supported by the ab initio calculations for Gd having magnetic moment of 7.1 µB and the calculated AFM band structure indicates that GdSbTe is a semimetal with bare density of states (0.36 states/eV fu) at the Fermi level, which is 10 times smaller than the measured one to suggest strong spin-fluctuation.
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We have obtained analytical expressions for the radiative decay rate of the spontaneous emission of a chiral molecule located near a dielectric spherical particle with a chiral nonconcentric spherical shell made of a bi-isotropic material. Our numerical and graphical analyses show that material composition, thickness and degree of non-concentricity of the shell can influence significantly the spontaneous radiation of the chiral molecule. In particular, the radiative decay rates can differ in orders of magnitude for a chiral molecule located near the thin and thick parts of a nonconcentric shell as well as near a concentric shell made of chiral metamaterial. We also find that the radiative decay rates of the "right" and "left" chiral molecule enantiomers located near a nanoparticle with a chiral metamaterial shell can differ pronouncedly from each other. Our findings therefore suggest a way to tune the spontaneous emission of chiral molecules by varying the material composition, thickness and degree of non-concentricity of the shell in the nearby composite nanoparticle and also to enhance the chirality selection of chiral molecules in racemic mixtures.
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The quantum anomalous Hall (QAH) phase is a two-dimensional bulk ferromagnetic insulator with a nonzero Chern number in the presence of spin-orbit coupling (SOC) but in the absence of applied magnetic fields. Associated metallic chiral edge states host dissipationless current transport in electronic devices. This intriguing QAH phase has recently been observed in magnetic impurity-doped topological insulators, albeit, at extremely low temperatures. Based on first-principles density functional calculations, here we predict that layered rhodium oxide K_{0.5}RhO_{2} in the noncoplanar chiral antiferromagnetic state is an unconventional three-dimensional QAH insulator with a large band gap and a Néel temperature of a few tens of Kelvins. Furthermore, this unconventional QAH phase is revealed to be the exotic quantum topological Hall effect caused by nonzero scalar spin chirality due to the topological spin structure in the system and without the need of net magnetization and SOC.
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By both experimental measurements and theoretical calculations, we investigated the magnetic and electronic properties of Li2Cu(WO4)2 as a tungstate-bridged quasi-one-dimensional (1D) copper spin-(1/2) chain system. Interestingly, magnetic susceptibility χ(T) and specific heat measurements show that the system undergoes a three-dimensional antiferromagnetic (AF)-like ordering at TN ≈ 3.7 K, below a broad χ(T) maximum at â¼8.9 K indicating a low-dimensional short-range AF spin correlation. Bonner-Fisher model fitting of χ(T) leads to an AF intrachain exchange constant of J/kB = 15.8 ± 0.1 K, and mean-field theory estimation gives an interchain coupling constant of Jâ¥/kB = 1.6 K, which supports the quasi-1D nature of this spin system. Theoretical evaluation of exchange coupling constants within the generalized gradient approximation (GGA) plus on-site Coulomb interaction (U) shows that the dominant AF exchange interaction is of â¼13.9 K along the a-axis with weak interchain coupling, in agreement with the experimental result of a quasi-1D spin-(1/2) chain system. The GGA+U calculations also predict that Li2Cu(WO4)2 is a charge transfer-type AF semiconductor with a direct band gap of 1.5 eV.
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We study the surface plasmon modes in a silver double-nanowire system by employing the eigenmode analysis approach based on the finite element method. Calculated dispersion relations, surface charge distributions, field patterns and propagation lengths of ten lowest energy plasmon modes in the system are presented. These ten modes are categorized into three groups because they are found to originate from the monopole-monopole, dipole-dipole and quadrupole-quadrupole hybridizations between the two wires, respectively. Interestingly, in addition to the well studied gap mode (mode 1), the other mode from group 1 which is a symmetrically coupled charge mode (mode 2) is found to have a larger group velocity and a longer propagation length than mode 1, suggesting mode 2 to be another potential signal transporter for plasmonic circuits. Scenarios to efficiently excite (inject) group 1 modes in the two-wire system and also to convert mode 2 (mode 1) to mode 1 (mode 2) are demonstrated by numerical simulations.
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Nanopartículas del Metal/química , Modelos Químicos , Nanocables/química , Plata/química , Resonancia por Plasmón de Superficie/métodos , Simulación por Computador , Luz , Dispersión de RadiaciónRESUMEN
We propose to use double negative (DNG) metamaterial slabs to build effective super-absorbers and perfect nanodetectors for single divergent sources. We demonstrate by numerical simulations that an absorbing nanoparticle properly placed inside a DNG slab back-covered with a perfect electric conductor or perfect magnetic conductor mirror can absorb up to 100% radiation energy of a single dipole source placed outside the slab. Furthermore, we also show that even the simple DNG slab without any absorbing nanoparticle could be used as a perfect absorber for both plane and divergent beams. The proposed systems may focus the radiation in nanoscale and thus have applications in optical nanodevices for a variety of different purposes.
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Lentes , Nanopartículas/química , Nanotecnología/instrumentación , Fotometría/instrumentación , Refractometría/instrumentación , Transductores , Absorción , Diseño de Equipo , Análisis de Falla de Equipo , Nanopartículas/efectos de la radiación , Nanopartículas/ultraestructura , Tamaño de la PartículaRESUMEN
We combine theory and experiment to demonstrate that a carefully designed gradient meta-surface supports high-efficiency anomalous reflections for near-infrared light following the generalized Snell's law, and the reflected wave becomes a bounded surface wave as the incident angle exceeds a critical value. Compared to previously fabricated gradient meta-surfaces in infrared regime, our samples work in a shorter wavelength regime with a broad bandwidth (750-900 nm), exhibit a much higher conversion efficiency (â¼80%) to the anomalous reflection mode at normal incidence, and keep light polarization unchanged after the anomalous reflection. Finite-difference-time-domain (FDTD) simulations are in excellent agreement with experiments. Our findings may lead to many interesting applications, such as antireflection coating, polarization and spectral beam splitters, high-efficiency light absorbers, and surface plasmon couplers.
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Astrocytes play an important role in the pathogenesis of Alzheimer's disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD. We found the depletion of some important metabolites (acetyl-coenzyme A, aspartate, pyruvate, 2-oxoglutarate, glutamine, and others), as well as the inhibition of some metabolic fluxes (glycolysis and tricarbocylic acid cycle, glutamate metabolism) in astrocytes of AD. The abnormality of glutamate metabolism in astrocytes is unique and important. Downregulation of GLUL (GS) and GLUD1 (GDH) may be the cause of glutamate alterations in astrocytes in AD. These results provide a basis for understanding the characteristic changes in astrocytes in AD and provide ideas for the study of AD pathogenesis.
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Topologically protected photonic edge states offer unprecedented robust propagation of photons that are promising for waveguiding, lasing, and quantum information processing. Here, we report on the discovery of a class of hybrid topological photonic crystals that host simultaneously quantum anomalous Hall and valley Hall phases in different photonic band gaps. The underlying hybrid topology manifests itself in the edge channels as the coexistence of the dual-band chiral edge states and unbalanced valley Hall edge states. We experimentally realize the hybrid topological photonic crystal, unveil its unique topological transitions, and verify its unconventional dual-band gap topological edge states using pump-probe techniques. Furthermore, we demonstrate that the dual-band photonic topological edge channels can serve as frequency-multiplexing devices that function as both beam splitters and combiners. Our study unveils hybrid topological insulators as an exotic topological state of photons as well as a promising route toward future applications in topological photonics.
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Based on both analytical dipole model analyses and numerical simulations, we propose a concept of coherent perfect nanoabsorbers (CPNAs) for divergent beams. This concept makes use of the properties of a slab with negative refraction and small losses. The proposed CPNA device would allow focusing radiation in nanoscale regions, and hence could be applied in optical nanodevices for such diverse purposes as reading the results of quantum computation which is based on single photon qubits.
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We demonstrate a self-assembly strategy for fabricating three dimensional (3D) metamaterials. This strategy represents the desired 3D curving prongs of the split ring resonators (SRRs) erected by metal stress force with appropriate thin film parameters. Transmittance spectra and field patterns corresponding to each resonance modes are calculated by finite element method (FEM). The eigen-modes of the SRRs can be excited by normal illumination with polarization state parallel to the erected SRRs, which are unlike for the cases of planar SRRs. This method opens a promising fabrication process for the application of tailored 3D SRRs.