Comprehensive characterization of Epimedium-Rhizoma drynariae herb pair in rat plasma, urine, and feces metabolic profiles by UHPLC-Q-Orbitrap HRMS combined with diagnostic extraction strategy and multicomponent pharmacokinetic study by UHPLC-MS/MS.

Epimedium-Rhizoma drynariae (EP-RD) was a well-known herb commonly used to treat bone diseases in traditional Chinese medicine. Nevertheless, there was incomplete pharmacokinetic behavior, metabolic conversion and chemical characterization of EP-RD in vivo. Therefore, this study aimed to establish metabolic profiles combined with multicomponent pharmacokinetics to reveal the in vivo behavior of EP-RD. Firstly, the diagnostic product ions (DPIs) and neutral losses (NLs) filtering strategy combined with UHPLC-Q-Orbitrap HRMS for the in vitro chemical composition of EP-RD and metabolic profiles of plasma, urine, and feces after oral administration of EP-RD to rats were proposed to comprehensively characterize the 47 chemical compounds and the 97 exogenous in vivo (35 prototypes and 62 metabolites), and possible biotransformation pathways of EP-RD were proposed, which included phase I reactions such as hydrolysis, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, isomerization, and demethylation and phase II reactions such as glucuronidation, acetylation, methylation, and sulfation. Moreover, a UHPLC-MS/MS quantitative approach was established for the pharmacokinetic analysis of seven active components: magnoflorine, epimedin A, epimedin B, epimedin C, icariin, baohuoside II, and icariin II. Results indicated that the established method was reliably used for the quantitative study of plasma active ingredients after oral administration of EP-RD in rats. Compared to oral EP alone, the increase in area under curves and maximum plasma drug concentration (P < 0.05). This study increased the understanding of the material basis and biotransformation profiles of EP-RD in vivo, which was of great significance in exploring the pharmacological effects of EP-RD.

Chemoselectivity Strategy Based on B-Label Integrated with Tailored COF for Targeted Metabolomic Analysis of Short-Chain Fatty Acids by UHPLC-MS/MS.

Chemoselective extraction strategy is an emerging and powerful means for targeted metabolomics analysis, which allows for the selective identification of biomarkers. Short-chain fatty acids (SCFAs) as functional metabolites for many diseases pose challenges in qualitative and quantitative analyses due to their high polarity and uneven abundance. In our study, we proposed the B-labeled method for the derivatization of SCFAs using easily available 3-aminobenzeneboronic acid as the derivatization reagent, which enables the introduction of recognition unit (boric acid groups). To analyze the B-labeled targeted metabolites accurately, cis-diol-based covalent organic framework (COF) was designed to specifically capture and release target compounds by pH-response borate affinity principle. The COF synthesized by the one-step Schiff base reaction possessed a large surface area (215.77 m2/g), excellent adsorption capacity (774.9 µmol/g), good selectivity, and strong regeneration ability (20 times). Combined with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, our results indicated that the detection sensitivities of SCFAs increased by 1.2-2500 folds compared with unlabeled method, and the retention time and isomer separation were improved. Using this strategy, we determined twenty-six SCFAs in the serum and urine of rats in four groups about osteoporosis and identified important biomarkers related to the tricarboxylic acid cycle and fatty acid metabolism pathways. In summary, UHPLC-MS/MS based on B-labeled derivatization with tailored COF strategy shows its high selectivity, excellent sensitivity, and good chromatographic behavior and has remarkable application prospect in targeted metabolomics study of biospecimens.

Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic-pituitary-gonadal axis of kidney-yang-deficiency-syndrome rats.

Modern studies have shown that neuroendocrine disorders caused by the dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis are one of the important pathogenetic mechanisms of kidney-yang-deficiency-syndrome (KYDS). The preventive effect of Gushudan on KYDS has been reported, but its regulatory mechanisms on the HPG axis have not been elucidated. In this study, we developed an integrated untargeted and targeted metabolomics analysis strategy to investigate the regulatory mechanism of Gushudan on the HPG axis in rats with KYDS. In untargeted metabolomics, we screened 14 potential biomarkers such as glycine, lysine, and glycerol that were significantly associated with the HPG axis. To explore the effect of changes in the levels of potential biomarkers on KYDS, all of them were quantified in targeted metabolomics. With the quantitative results, correlations between potential biomarkers and testosterone, a functional indicator of the HPG axis, were explored. The results showed that oxidative stress, inflammatory response, and energy depletion, induced by metabolic disorders in rats, were responsible for the decrease in testosterone levels. Gushudan improves metabolic disorders and restores testosterone levels, thus restoring HPG axis dysfunction. This finding elucidates the special metabolic characteristics of KYDS and the therapeutic mechanism of Gushudan from a new perspective.

Integrated UHPLC-MS untargeted metabolomics and gut microbe metabolism pathway-targeted metabolomics to reveal the prevention mechanism of Gushudan on kidney-yang-deficiency-syndrome rats.

Gushudan (GSD) was a traditional Chinese prescription with the remarkable effect of kidney-tonifying and bone-strengthening. However, the potential prevention mechanisms of the GSD on kidney-yang-deficiency-syndrome (KYDS) and its regulation on gut microbe metabolism still need to be further systematically investigated. This study established untargeted urinary metabolomics based on RP/HILIC-UHPLC-Q-Orbitrap HRMS and combined with multivariate statistical analysis to discover differential metabolites and key metabolic pathways. And the gut microbe metabolism pathway-targeted metabolomic based on HILIC-UHPLC-MS/MS was developed and validated to simultaneously determine 15 gut microbe-mediated metabolites in urine samples from the control group (CON), KYDS model group (MOD), GSD-treatment group (GSD) and positive group (POS). The results showed that a total of 36 differential metabolites were discovered in untargeted metabolomics. These differential metabolites included proline, cytosine, butyric acid and nicotinic acid, which were primarily involved in the gut microbe metabolism, amino acid metabolism, energy metabolism and nucleotide metabolism. And GSD played a role in preventing KYDS by regulating these metabolic pathways. The targeted metabolomics found that the levels of 10 gut microbe-mediated metabolites had significant differences in different groups. Among them, compared with the CON group, the levels of lysine, tryptophan, phenylacetylglycine and hippuric acid were increased in the MOD group, while the levels of threonine, leucine, dimethylamine, trimethylamine, succinic acid and butyric acid were decreased, which verified the disorders of gut microbe metabolism in the KYDS rats and GSD had a significant regulatory effect on this disorder. As well as by comparing analysis, it was found that the experimental results were consistent with previous metabolomics and microbiomics of fecal samples. Therefore, this integrated strategy of untargeted and targeted metabolomics not only elucidated the potential prevention mechanism of GSD on KYDS, but also provided a scientific basis for GSD preventing KYDS via the "gut-kidney" axis.

Topological super-modes engineering with acoustic graphene plasmons.

Acoustic graphene plasmons (AGPs) in a graphene-dielectric-metal structure possess extreme field localization and low loss, which have promising applications in strong photon-matter interaction and integrated photonic devices. Here, we propose two kinds of one-dimensional crystals supporting propagating AGPs with different topological properties, which is confirmed by the Zak phase calculations and the electric field symmetry analysis. Moreover, by combining these two plasmonic crystals to form a superlattice system, the super-modes exist because of the coupling between isolated topological interface states. A flat-like dispersion of super-modes is observed by designing the superlattice. These results should find applications in optical sensing and integrating photonic devices with plasmonic crystals.

Giant Second Harmonic Generation from Membrane Metasurfaces.

Metasurfaces have emerged as a fascinating framework for nonlinear optics, which have advantages of a compact footprint and unprecedented flexibility in manipulating light. But their nonlinear responses are generally limited by the short interaction lengths with light. Therefore, further enhancement is highly desired for building high-efficiency nonlinear devices. Here, we experimentally demonstrate a record high second harmonic generation (SHG) efficiency of 2.0 × 10-4 using lithium niobate (LN) membrane metasurfaces. Benefiting from the large refractive index contrast in the vertical direction and high fabrication quality, distinct spectral resonances and tight field confinements in the LN layer were achieved. Strong SHG peaks resulting from pump resonances of the metasurfaces were observed. Our nonlinear efficiency is more than 2 orders of magnitude larger than previously reported LN metasurfaces. The results inspire a way to improve the efficiency of nonlinear metasurfaces for ultracompact nonlinear light sources in applications of nonlinear holography, Li-Fi, beam shaping, etc.

Intelligent metasurfaces can recognize objects.

An on-chip optical neural network is built using metasurfaces, which can recognize objects with high accuracy.

Metasurfaces with high-Q resonances governed by topological edge state.

Achieving high-quality (Q)-factor resonances in metasurfaces is essential for various applications, including nano-lasers, nonlinear optics, and quantum optics. In this work, we propose a high-Q metasurface using a topological strategy: constructing the metasurface by stacking two conjugated nanopillar arrays with different topological invariants. Our study shows that a topological edge state steadily appears at the interfaces of the nanopillars, and a sharp transmission resonance with a Q-factor of more than 1000 can be obtained. The sensing application of such high-Q topological metasurface is also demonstrated, whose figure of merit reaches approximately 145. The proposed strategy and underlying theory can open up new avenues to realize ultrasharp resonances, which can promote numerous potential applications, such as biosensing, optical modulation, and slow-light devices.

All-optical modulation of quantum states by nonlinear metasurface.

Metasurfaces have proven themselves an exotic ability to harness light at nano-scale, being important not only for classical but also for quantum optics. Dynamic manipulation of the quantum states is at the heart of quantum information processing; however, such function has been rarely realized with metasurfaces so far. Here, we report an all-optical dynamic modulation of the photonic quantum states using the nonlinear metasurface. The metasurface consists of a metallic nanostructure combined with a photoisomerizable azo layer. By tuning the plasmonic resonance through optically switching the azo molecules between their binary isomeric states, we have realized dynamic control of transmission efficiencies of orthogonally polarized photons and also the phase delay between them, thereby an entangled state was efficiently controlled. As an illustration, a quantum state distillation has been demonstrated to recover a Bell state from a non-maximally entangled one to that with fidelities higher than 98%. Our work would enrich the functions of the metasurface in the quantum world, from static to dynamic modulation, making the quantum metasurface going practical.

Strong in-plane scattering of acoustic graphene plasmons by surface atomic steps.

Acoustic graphene plasmons (AGPs) have ultrastrong field confinement and low loss, which have been applied for quantum effect exploration and ångström-thick material sensing. However, the exploration of in-plane scattering of AGPs is still lacking, although it is essential for the manipulation of ultraconfined optical fields down to atomic level. Here, by using scattering-type scanning near-field optical microscopy (s-SNOM), we show that the mid-infrared AGPs can be strongly scattered by atomic level height steps, even though the step height of the scatterer is four orders of magnitude smaller than the incident free wavelength. This effect can be attributed to larger back scattering of AGPs than that of the traditional graphene plasmons. Besides, the scattering of AGPs by individual scatterers can be controlled via electrical back gating. Our work suggests a feasible way to control confined optical fields with atomic level height nanostructures, which can be used for ultra-compacted strong light-matter interactions.

Error analysis of a rotating-metasurface polarimeter.

Polarimeters, which measure the polarization states of light directly, are essentially desired in many areas of science and technology. In our previous work, we have constructed a polarimeter based on a rotating-metasurface, and the polarization Stokes parameters of the light were measured with the known Mueller elements of the metasurface. Here, we further perform the error analysis of the metasurface polarimeter. The errors in the measured Stokes parameters have been formulated for the errors in Mueller elements of the metasurface. This analysis can be used to evaluate and minimize the errors of the metasurface polarimeter.

Tunable terahertz topological edge and corner states in designer surface plasmon crystals.

In this work, we study topological edge and corner states in two-dimensional (2D) Su-Schrieffer-Heeger lattices from designer surface plasmon crystals (DSPCs), where the vertical confinement of the designer surface plasmons enables signal detection without the need of additional covers for the sample. In particular, the formation of higher-order topological insulator can be determined by the two-dimensional Zak phase, and the zero-dimensional subwavelength corner states are found in the designed DSPCs at the terahertz (THz) frequency band together with the edge states. Moreover, the corner state frequency can be tuned by modifying the defect strength, i.e., the location or diameter of the corner pillars. This work may provide a new approach for confining THz waves in DSPCs, which is promising for the development of THz topological photonic integrated devices with high compactness, robustness and tunability.

Nanoinfrared Characterization of Bilayer Graphene Conductivity under Dual-Gate Tuning.

Dual-gate tuning on two-dimensional (2D) heterostructures can provide independent control of the carrier concentration and interlayer electrostatic potential, yielding novel electronic and optical properties. In this paper, by utilizing monolayer graphene as both the top gate and a plasmon wavelength magnifier, the optical properties of bilayer graphene (BLG) under dual-gate are quantitatively investigated by nanoinfrared imaging. The hybrid optical modes in the vertically coupled two-layer system are imaged from scattering-type scanning near-field microscopy (s-SNOM). Moreover, plasmon dispersion behaviors under varied dual-gate tuning are explored and explained well with theoretical ones employing tight binding approximation, which reveals the flexibility in individually manipulating the Fermi energy and bandgap. Especially, electron-hole asymmetry in BLG is verified from experiments. Our studies pave route for quantitative near-field investigation of superlattice, topological boundaries, and other emergent phenomena in graphene-based 2D heterostructures.

Machine learning powered ellipsometry.

Ellipsometry is a powerful method for determining both the optical constants and thickness of thin films. For decades, solutions to ill-posed inverse ellipsometric problems require substantial human-expert intervention and have become essentially human-in-the-loop trial-and-error processes that are not only tedious and time-consuming but also limit the applicability of ellipsometry. Here, we demonstrate a machine learning based approach for solving ellipsometric problems in an unambiguous and fully automatic manner while showing superior performance. The proposed approach is experimentally validated by using a broad range of films covering categories of metals, semiconductors, and dielectrics. This method is compatible with existing ellipsometers and paves the way for realizing the automatic, rapid, high-throughput optical characterization of films.

Linewidth narrowing of aluminum breathing plasmon resonances in Bragg grating decorated nanodisks.

Plasmon resonances with high-quality are of great importance in light emission control and light-matter interactions. Nevertheless, inherent ohmic and radiative losses usually hinder the plasmon performance of metallic nanostructures, especially for aluminum (Al). Here we demonstrate a Bragg grating decorated nanodisk to narrow the linewidth of breathing plasmon resonances compared with a commensurate nanodisk. Two kinds of plasmon resonant modes and the corresponding mode patterns are investigated in cathodoluminescence (CL) depending on the different electron bombardment positions, and the experimental results agree well with full wave electromagnetic simulations. Linewidth narrowing can be clearly understood using an approximated magnetic dipole model. Our results suggest a feasible mechanism for linewidth narrowing of plasmon resonances as well as pave the way for in-depth analysis and potential applications of Al plasmon systems.

Phase-Transition Optical Activity in Chiral Metamaterials.

Optical activity from chiral metamaterials is both fundamental in electrodynamics and useful for polarization control applications. It is normally expected that due to infinitesimally small thickness, two-dimensional (2D) planar metamaterials cannot introduce large optical rotations. Here, we present a new mechanism to achieve strong optical rotation up to 90° by evoking phase transition in the 2D metamaterials through tuning coupling strength between meta-atoms. We analytically elucidate such phenomenon by developing a model of phase-transition coupled-oscillator array. And we further corroborate our ideas with both numerical simulations and experiments. Our findings would pave a new way for applying the concept of phase transition in photonics for designing novel optical devices for strong polarization controls and other novel applications.

Multifunctional and tunable trigate graphene metamaterial with "Lakes of Wada" topology.

Many plasmon-induced transparency (PIT) metamaterials previously reported had limited functions. Their tunabilities were realized by complex discrete structures, which greatly increased the difficulty and cost of device fabrication and adversely affected their resonance characteristics. It is an open question to adjust the Fermi levels of many graphene patterns with only a few in-plane electrodes. We propose and numerically study a novel electrically tunable and multifunctional trigate graphene metamaterial (TGGM) based on the concept of "Lakes of Wada". Benefiting from the trigate regulation, our proposed TGGM turns out to exhibit excellent characteristics, that can not only be used for terahertz band-stop filter, terahertz refractive index sensor, near-field optical switch, slow-light device, but also for double PIT window metamaterial with broad transparency windows and large tunable frequency range.

Ultrastrong coupling of CdZnS/ZnS quantum dots to bonding breathing plasmons of aluminum metal-insulator-metal nanocavities in near-ultraviolet spectrum.

Strong coupling originating from excitons of quantum dots and plasmons in nanocavities can be realized at room temperature due to the large electromagnetic field enhancement of plasmons, offering building blocks for quantum information systems, ultralow-power switches and lasers. However, most of the current strong coupling effects were realized by the interaction between excitons and far-field light excited bright plasmon modes in the visible range. Beyond that, there is still a lack of direct imaging of polariton modes at the nanoscale. In this work, by using cathodoluminescence, ultrastrong coupling with Rabi splitting exceeding 1 eV between bonding breathing plasmons of aluminum (Al) metal-insulator-metal (MIM) cavities and excited states of CdZnS/ZnS quantum dots was observed in the near-ultraviolet (UV) spectrum. Further, the hybridization of the QDs excitons and bonding breathing plasmonic modes is verified by deep-subwavelength images of polaritonic modes in real-space. Analytic analysis based on the coupled oscillator model and full-wave electromagnetic simulations is consistent with our experimental results. Our work not only indicates the great potential of electron excited plasmon modes for strong coupling applications, but also extends the polaritonic frequency to the UV range with Al nanocavities.

Tailorable Dynamics in Nonlinear Optical Metasurfaces.

Controlling light with light is essential for all-optical switching, data processing in optical communications and computing. Until now, all-optical control of light has relied almost exclusively on nonlinear optical interactions in materials. Achieving giant nonlinearities under low light intensity is essential for weak-light nonlinear optics. In the past decades, such weak-light nonlinear phenomena have been demonstrated in photorefractive and photochromic materials. However, their bulky size and slow speed have hindered practical applications. Metasurfaces, which enhance light-matter interactions at the nanoscale, provide a new framework with tailorable nonlinearities for weak-light nonlinear dynamics. Current advances in nonlinear metasurfaces are introduced, with a special emphasis on all-optical light controls. The tuning of the nonlinearity values using metasurfaces, including enhancement and sign reversal is presented. The tailoring of the transient behaviors of nonlinearities in metasurfaces to achieve femtosecond switching speed is also discussed. Furthermore, the impact of quantum effects from the metasurface on the nonlinearities is introduced. Finally, an outlook on the future development of this energetic field is offered.