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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165554, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513833

RESUMO

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

2.
J Nanosci Nanotechnol ; 20(4): 2395-2401, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492253

RESUMO

In this paper, ß-Ga2O3 nanowires were synthesized by vapor transport method at different temperatures. The as-prepared samples were analyzed for crystal structure by X-ray diffraction (XRD), transmission electron microscopy (TEM) and selected area electron diffraction (SAED), and for morphology using scanning electron microscopy (SEM). The results show that the Ga2O3 nanowires present a monoclinic structure, the length and diameter of the Ga2O3 nanowires increased with the growth temperature. A majority of the Ga2O3 nanowires present longitudinal twinning structures. A broad photoluminescence emission band was observed from the Ga2O3 nanowires at room temperature, which is caused by different kinds of vacancy defects. Our study shows an unusual twinning structure of ß-Ga2O3 nanowires, which may be helpful to understand the growth mechanism of nanowires.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31758480

RESUMO

This research aims to examine the empirical cointegration, long-run and short-run dynamics, and causal relationships between trade openness, environmental regulation, and human capital level in China throughout 1990-2016. Based on the ARDL Bounds Testing method, the empirical results confirmed long-run cointegration between trade openness, environmental regulation, and human capital level. Environmental regulation and trade openness have a significant positive impact on the human capital level, and environmental regulation has a U-shaped effect on human capital accumulation. The Granger causality test results indicate that environmental regulation Granger causes human capital level, the human capital level Granger causes trade openness, and trade openness and environmental regulation have a bidirectional relationship. This research brings new contributions to sustainable development theory.

4.
Planta Med ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31766070

RESUMO

The endophytic microbiome in medicinal plants is rich and diverse, but few studies have followed the endophytic microbiome of medicinal plants in different tissues with their growth. In this study, we examined the endophytic bacterial and fungal community structures associated with both the stem and root compartments of Dendrobium huoshanense at different growth years via high-throughput sequencing of 16S rRNA genes and nrDNA fragments of internal transcribed spacer regions. Results indicated that more diverse prokaryotic and fungal operational taxonomic units were detected in roots than in stems, and the alpha diversity of endophytic prokaryotic significantly differed among the 1-, 2-, and 3-year-old roots. The dominant bacterial phyla Proteobacteria Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteria, and fungal phyla Ascomycota, Basidiomycota, and Ascomycota were detected in the stems and roots with 3 growth years. Moreover, linear discriminant effect size analysis revealed 138 differentially abundant taxonomic clades in the bacterial level, and 197 in the fungal level in six groups. Our results provide evidence for endophytic microbiota communities depending on the tissues and growth years of D. huoshanense. The results from this study should be useful to better understand medicinal plant-microbe interactions.

5.
Nat Commun ; 10(1): 5182, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729388

RESUMO

The development of enantiodivergent catalysis for the preparation of both enantiomers of a chiral compound is of importance in pharmaceutical and bioorganic chemistry. With the design of a class of reactive and stereoselective organocatalysts, acyclic chiral secondary amines, a method for achieving the enantiodivergence is developed simply by changing the secondary N-i-Bu- to N-Me-group within the catalyst architecture while maintaining the same absolute configuration of the catalysts, which modulates the catalyst conformation. This catalyst-controlled enantiodivergent method not only enables challenging asymmetric transformations to occur in an enantiodivergent manner but also features a high level of stereocontrol and broad scope that is demonstrated in eight different reactions (90 examples), all delivering both enantiomers of a range of structurally diverse products including hitherto less accessible, yet important, compounds in good yields with high stereoselectivities.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31742430

RESUMO

Background: Recently, signal peptide-CUB-EGF-like domain containing protein 3 (SCUBE3) has been found to be associated with the development of several cancers. However, the biological role of SCUBE3 in breast cancer progression has not been reported. Materials and Methods: Western blotting and quantitative real-time polymerase chain reaction were used to measure the expressions of SCUBE3, TGF-ß (transforming growth factor-ß) signaling pathway markers, and epithelial-mesenchymal transition markers. The influence of SCUBE3 on the breast cancer cell proliferation, invasion, and migration was detected using methyl thiazolyl tetrazolium, wound healing, colony formation, and transwell assay. The role of SCUBE3 in vivo was confirmed using tumor xenograft experiment. Results: SCUBE3 expression was markedly increased in breast cancer cells and tissues. Knockdown of SCUBE3 suppressed cell growth, invasion, and migration, while SCUBE3 overexpression promoted cell growth, invasion, and migration in breast cancer cells. In addition, TGF-ß1 and its downstream proteins were positively regulated by SCUBE3, and the promotion effect on TWIST1 expression induced by pcDNA3.1-SCUBE3 can be reversed by TGF-ß1 inhibitor in breast cancer cell lines. Moreover, silencing of SCUBE3 suppressed breast cancer cell growth and tumorigenesis through reducing TGF-ß1 in vivo. Conclusion: Knockdown of SCUBE3 downregulated TGF-ß1 and TWIST1 expression, thereby inhibiting breast cancer cell growth and tumorigenesis.

7.
Neurosci Bull ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31732865

RESUMO

Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear. Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI. ESCS also significantly increased the myelinated area at 28 days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase, an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rhBMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI, and rhBMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.

8.
J Asian Nat Prod Res ; : 1-7, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738087

RESUMO

Bistachybotrysin K (1), one new phenylspirodrimane dimer with a central 6/7 oxygen heterocycle core, was isolated from the fungus Stachybotrys chartarum CGMCC 3.5365. Its structure was elucidated by extensive spectroscopic data and single-crystal X-ray diffraction. Compound 1 showed significant cytotoxicity against human tumor cell lines HCT116, NCI-H460, BGC823, Daoy, and HepG2 with IC50 values in the range of 1.1-4.7 µM.

9.
Clin Chim Acta ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626762

RESUMO

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) and its receptor, lectin-like ox-LDL receptor-1 (LOX-1) are involved in the pathogenesis of atherosclerosis. Expression of LOX-1 was substantially raised in the basilar arterial wall of subarachnoid hemorrhage (SAH) rabbits. We ascertained the relationship between serum soluble LOX-1 concentrations and functional outcome after human aneurysmal SAH. METHODS: We enrolled 94 aneurysmal SAH patients and 94 healthy controls. Serum soluble TOX-1 concentrations were quantified using commercial enzyme-linked immunosorbent assay kit. A poor outcome was defined as Glasgow outcome scale score of 1-3. RESULTS: Median values of serum soluble LOX-1 in stroke patients were significantly higher than those in controls (1.5 vs. 0.4 ng/ml, P < 0.001). Thirty patients (31.9%) had a poor outcome at 6 months after stroke. Serum soluble LOX-1 was a strong predictor of poor outcome (OR 5.20, 95% CI 1.25-22.04). Serum soluble LOX-1 concentrations exhibited a significant discriminatory capability (area under curve 0.811, 95% confidence interval 0.717-0.884). The predictive powers of World Federation of Neurological Surgeons grade, Hunt-Hess grade, modified Fisher grade, and serum soluble LOX-1 concentrations were comparable (all P > 0.05). CONCLUSIONS: Serum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.

10.
J Cell Physiol ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31625162

RESUMO

Haspin (Haploid Germ Cell-Specific Nuclear Protein Kinase) is a serine/threonine kinase pertinent to normal mitosis progression and mitotic phosphorylation of histone H3 at threonine 3 in mammalian cells. Different classes of small molecule inhibitors of haspin have been developed and utilized to investigate its mitotic functions. We report herein that applying haspin inhibitor CHR-6494 or 5-ITu at the G1/S boundary could delay mitotic entry in synchronized HeLa and U2OS cells, respectively, following an extended G2 or the S phase. Moreover, late application of haspin inhibitors at S/G2 boundary is sufficient to delay mitotic onset in both cell lines, thereby, indicating a direct effect of haspin on G2/M transition. A prolonged interphase duration is also observed with knockdown of haspin expression in synchronized and asynchronous cells. These results suggest that haspin can regulate cell cycle progression at multiple stages at both interphase and mitosis.

11.
Cell Cycle ; 18(23): 3288-3299, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31615303

RESUMO

Long noncoding RNA (lncRNA) regulate many biological processes ranging from tumorigenesis to cancer metastasis. MicroRNA-223 (miR-223) acts as a novel tumor suppressor in bladder cancer (BC), however its target genes involved in BC, the molecular mechanisms governing its expression remain largely unknown. Both gain-of-function and loss of function experiments were performed to investigate the role of miR-223 in BC cells. The effects of miR-223 on BC progression were assessed using in vivo subcutaneous xenografts. The luciferase reporter assays were utilized to confirm the putative miR-223-binding site in the 3'-UTR of oncogene HSP90B1. The luciferase reporter assays and RNA immunoprecipitation assays were used to analyze the association between miR-223 and lncRNA DXL6-AS1 in BC cells. The expression of miR-223 was remarkably decreased in BC samples and BC cells. High miR-223 expression was correlated with favorable patient survival. BC cell growth in vivo was delayed by miR-223 overexpression. HSP90B1 was a direct target of miR-223 in BC cells, and the suppression of BC cell growth and invasion induced by miR-223 could be rescued by overexpression of HSP90B1. Moreover, lncRNA DXL6-AS1 was upregulated in BC tissues and functioned as a sponge for miR-223 and reduced its expression in BC cells, thereby enhancing cell proliferation and invasion. Forced expression of miR-223 could reverse the oncogenic effects of DXL6-AS1 on BC cell proliferation and invasion. Our study suggested that DLX6-AS1-mediated silencing of miR-223 promotes BC progression through the upregulation of HSP90B1.

12.
J Cell Mol Med ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31568643

RESUMO

Renal cell carcinoma (RCC) is a heterogeneous histological disease and it is one of the most common kidney cancer. The treatment of RCC has been improved for the past few years, but its mortality still remains high. Chelerythrine (CHE) is a natural benzo[c]phenanthridine alkaloid and a widely used broad-range protein kinase C inhibitor which has anti-cancer effect on various types of human cancer cells. However, its effect on RCC has not been fully elucidated. In this study, we evaluated the effect and mechanism of CHE on RCC cells. Our study showed that CHE induced colony formation inhibition and G2/M cell cycle arrest in a dose-dependent manner in RCC cells. In addition, CHE increased cellular ROS level, leading to endoplasmic reticulum (ER) stress, inactivating STAT3 activities and inducing apoptosis in RCC cells which were suppressed by NAC, a special ROS inhibitor. We further found that both knockdown of ATF4 protein and overexpression of STAT3 protein could reduce CHE-induced apoptosis in Caki cells. These results demonstrated that the apoptosis induced by CHE was mediated by ROS-caused ER stress and STAT3 inactivation. Collectively, our studies provided support for CHE as a potential new therapeutic agent for the management of RCC.

13.
Acc Chem Res ; 52(11): 3064-3074, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31657899

RESUMO

Fluorophore probes are widely used for bioimaging in cells, tissues, and animals as well as for monitoring of multiple biological processes in complex environments. Such imaging properties allow scientists to make direct visualizations of pathological events and cellular targets. Conventional fluorescent molecules have been developed for several decades and achieved great successes, but their emissions are often weakened or quenched at high concentrations that might suffer from the aggregation-caused quenching (ACQ) effect, which reduces the efficiencies of their applications. In contrast to the ACQ effect, aggregation-induced emission (AIE) luminogens (AIEgens) display much higher fluorescence in aggregated states and possess various advantages such as low background, long-term tracking ability, and strong resistance to photobleaching. Therefore, AIEgens are employed as unique fluorescence molecules and building blocks for biosensing applications in the fields of ions, amino acids, carbohydrates, DNAs/RNAs, peptides/proteins, cellular organelles, cancer cells, bacteria, and so on. Quite a few of the above biosensing missions are accomplished by modular peptide-modified AIEgen probes (MPAPs) or modular DNA-modified AIEgen probes (MDAPs) because of the multiple capabilities of peptide and DNA modules, including solubility, biocompatibility, and recognition. Meanwhile, both electrostatic interactions and coupling reactions could provide efficient methods to construct different MPAPs and MDAPs, finally resulting in a large variety of biosensing probes. Those probes exhibit leading features of detecting nucleic acids or proteins and imaging mass biomolecules. For example, under modular design, peptide modules possessing versatile recognition abilities enable MPAPs to detect numerous targets, such as integrin αvß3, aminopeptidase N, MMP-2, MPO, H2O2, and so forth; MDAP could allow the imaging of mRNA in cells and tissue chips, suggesting the diagnostic functions of MDAP in clinical samples. Modular design offers a novel strategy to generate AIEgen-based probes and expedites functional biomacromolecules research. In this vein, here we review the progress on MPAPs and MDAPs in the most recent 10 years and highlight the modular design strategy as well as their advanced biosensing applications including briefly two aspects: (1) detection and (2) imaging. By the use of MPAPs/MDAPs, multiple bioanalytes can be efficiently analyzed at low concentrations and directly visualized through high-contrast and luminous imaging. Compared with MPAPs, the quantities of MDAPs are limited because of the difficult synthesis of long-length DNA strands. In future work, multifunctional of DNA sequences are needed to explore varieties of MDAPs for diverse biosensing purposes. At the end of this Account, some deficiencies and challenges are mentioned for briging more attention to accelerate the development of AIEgen-based probes.

14.
J Opt Soc Am A Opt Image Sci Vis ; 36(8): 1295-1305, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503554

RESUMO

We determine the validity domain of classical approximations to estimation variance of the degree of polarization (DOP), angle of polarization, and ellipticity (EOP), when the measurement matrix of the Stokes vector is a spherical 2 design and noise is additive, white, and Gaussian. We demonstrate that this domain of validity is quite large, so that these approximations can be used safely for back-of-the-envelope calculations. In the presence of strong noise, DOP and EOP approximations show, however, some limits. We thus derive other approximations with extended domain of validity that can account for the dependence of DOP and EOP estimation variance on actual DOP and EOP values. The obtained results are important for design and performance characterization of polarimeters.

15.
J Opt Soc Am A Opt Image Sci Vis ; 36(7): 1229-1240, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503962

RESUMO

Estimation variances of the main polarimetric parameters (Stokes vector, degree of polarization, azimuth, and ellipticity) are derived for arbitrary Stokes measurement matrices in the presence of additive and Poisson shot noise. The obtained theoretical expressions, which are rather involved, are checked extensively with Monte Carlo simulations and their physical meaning is interpreted. The great benefit of these formulas is to enable comparisons of polarimeter architectures on a quantitative basis. As an example, we compare the optimal architectures based on spherical designs with a suboptimal one that may be easier to implement.

16.
ACS Appl Mater Interfaces ; 11(42): 38405-38416, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31556594

RESUMO

Intervertebral disc degeneration associated back pain is the most common cause of disability worldwide; however, no safe and effective treatments have been available. Here, we report a new functionalized nanofullerene conjugated with a peptide that binds specifically to a formyl peptide receptor-1 (FPR-1) expressed on activated macrophages. The new nanoparticle (aka FT-C60) was synthesized by conjugating carboxyl-C60 with the primary amine group of the peptide with a fluorescence dye for easy detection. The new nanoparticle was characterized by X-ray photoelectron spectroscopy, mass spectroscopy, and gel electrophoresis. It possessed effective radical (hydroxyl and superoxide anions) scavenging capabilities in electron paramagnetic resonance spectroscopy. In cultured cells, the nanoparticle FT-C60 demonstrated preferential binding to FPR-1 on activated macrophages and significantly attenuated mRNA expressions of proinflammatory factors including interleukin-6, interleukin-1, tumor necrosis factor-alpha, and cyclooxygenase-2. In vivo animal studies exhibited that a single intravenous injection of FT-C60 effectively alleviated pain in an established mouse model of radiculopathy for up to post-operation day (POD) 12. Ex vivo near-infrared fluorescence imaging of the mouse spine confirmed the targeting property of FT-C60 toward the injured disc on POD 14. Quantitative analysis of histological staining on spine sections showed that nanoparticle FT-C60 dramatically reduced inflammation at the local injury site compared to injury only on POD 7. In summary, we developed a novel targeted nanoparticle for treatment of lumbar radiculopathy by systemic delivery. This is a first-of-its-kind study for developing a novel class of targeted and systemic nanoparticle therapeutics to treat degenerative disc diseases.

17.
Front Immunol ; 10: 1824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428103

RESUMO

Macrophages play a critical role in the pathogenesis of endotoxin shock by producing excessive amounts of pro-inflammatory cytokines. A pan-caspase inhibitor, zVAD, can be used to induce necroptosis under certain stimuli. The role of zVAD in both regulating the survival and activation of macrophages, and the pathogenesis of endotoxin shock remains not entirely clear. Here, we found that treatment of mice with zVAD could significantly reduce mortality and alleviate disease after lipopolysaccharide (LPS) challenge. Notably, in LPS-challenged mice, treatment with zVAD could also reduce the percentage of peritoneal macrophages by promoting necroptosis and inhibiting pro-inflammatory responses in macrophages. In vitro studies showed that pretreatment with zVAD promoted LPS-induced nitric oxide-mediated necroptosis of bone marrow-derived macrophages (BMDMs), leading to reduced pro-inflammatory cytokine secretion. Interestingly, zVAD treatment promoted the accumulation of myeloid-derived suppressor cells (MDSCs) in a mouse model of endotoxin shock, and this process inhibited LPS-induced pro-inflammatory responses in macrophages. Based on these findings, we conclude that treatment with zVAD alleviates LPS-induced endotoxic shock by inducing macrophage necroptosis and promoting MDSC-mediated inhibition of macrophage activation. Thus, this study provides insights into the effects of zVAD treatment in inflammatory diseases, especially endotoxic shock.

18.
Nanoscale ; 11(41): 19422-19428, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31393509

RESUMO

In metal-free carbon-fullerene-based or defective graphene-based electrocatalysts, pentagon rings are known to play a key role in boosting catalytic activities for the oxygen reduction reaction (ORR). However, the fundamental chemical mechanism underlying the remarkable catalytic effect of the pentagon rings towards the ORR is still not fully understood. Herein, we perform a comprehensive computational study of the catalytic activities of various carbon fullerenes and fullerene fragment species, all containing pentagon rings, by using the density functional theory (DFT) and computational hydrogen electrode (CHE) methods. We find that more active sites on carbon are associated with more neighbouring pentagon rings and stronger adsorption of the key intermediates of O*, OH* and OOH* for the ORR. Importantly, two C60-based fragments, namely, C60-frag1 and C60-frag2l, show a very high activity towards the ORR, as both yield overpotentials as low as 0.389 and 0.407 V, and entail suitable adsorption free energy of OH* and OOH* species. These desirable chemical properties of fullerene fragments can be attributed to the high-energy HOMO orbitals, induced by the low-symmetry fullerene-fragment structures. Both the number of neighbouring pentagon rings and the degree of overall symmetry of the fragment appear to be the two important factors that can be adjusted for the design of optimal metal-free carbon electrocatalysts towards high ORR activities.

19.
ACS Appl Mater Interfaces ; 11(35): 32025-32037, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31398285

RESUMO

Photocatalytic CO2 reduction to solar fuel is a promising route to alleviate the ever-growing energy crisis and global warming. Herein, to enhance photoconversion efficiency of CO2 reduction, a series of direct Z-scheme composites consisting of ß-AgVO3 nanoribbons and InVO4 nanoparticles (InVO4/ß-AgVO3) are prepared via a facile hydrothermal method and subsequent in situ growth process. The prepared InVO4/ß-AgVO3 composites exhibit enhanced photocatalytic activity for reduction of CO2 to CO under visible-light illumination. A CO evolution rate of 12.61 µmol·g-1·h-1 is achieved over the optimized 20% In-Ag without any cocatalyst or sacrificial agent, which is 11 times larger than that yielded by pure InVO4 (1.12 µmol·g-1·h-1). Moreover, the CO selectivity is more than 93% over H2 production from the side reaction of H2O reduction. Significantly, based on the results of electron spin resonance (ESR) and in situ irradiated XPS tests, it is proposed that the synthesized InVO4/ß-AgVO3 catalysts comply with the direct Z-scheme transfer mechanism. Significantly improved photocatalytic activities for selective CO2 reduction could be primarily ascribed to effective separation of photoinduced electron-hole pairs and enhanced reducibility of photoelectrons at the conduction band of InVO4. This work provides a new insight for constructing highly efficient photocatalytic CO2 reduction systems toward solar fuel generation.

20.
Adv Mater ; 31(41): e1904069, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420926

RESUMO

Metasurfaces are artificially engineered ultrathin structures that can finely tailor and control electromagnetic wavefronts. There is currently a strong interest in exploring their capability to lift some fundamental limitations dictated by Lorentz reciprocity, which have strong implications in communication, heat management, and energy harvesting. Time-varying approaches have emerged as attractive alternatives to conventional schemes relying on magnetic or nonlinear materials, but experimental evidence is currently limited to devices such as circulators and antennas. Here, the recently proposed concept of space-time-coding digital metasurfaces is leveraged to break reciprocity. Moreover, it is shown that such nonreciprocal effects can be controlled dynamically. This approach relies on inducing suitable spatiotemporal phase gradients in a programmable way via digital modulation of the metasurface-elements' phase repsonse, which enable anomalous reflections accompanied by frequency conversions. A prototype operating at microwave frequencies is designed and fabricated for proof-of-concept validation. Measured results are in good agreement with theory, hence providing the first experimental evidence of nonreciprocal reflection effects enabled by space-time-modulated digital metasurfaces. The proposed concept and platform set the stage for "on-demand" realization of nonreciprocal effects, in programmable or reconfigurable fashions, which may find several promising applications, including frequency conversion, Doppler frequency illusion, optical isolation, and unidirectional transmission.

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