Engineering of the Fano resonance spectral response with non-Hermitian metasurfaces by navigating between exceptional point and bound states in the continuum conditions.

We address the engineering of Fano resonances and metasurfaces, by placing it in the general context of open non-Hermitian systems composed of coupled antenna-type resonators. We show that eigenfrequency solutions obtained for a particular case of scattering matrix are general and valid for arbitrary antenna radiative rates, thanks to an appropriate transformation of parametric space by simple linear expansion and rotation. We provide evidence that Parity-Time symmetry phase transition path and bound states in continuum (BIC) path represent the natural axis of universal scattering matrix solutions in this parametric coupling-detuning plane and determine the main characteristics of Fano resonance. Specifically, we demonstrate the control of asymmetry and sharpness of Fano resonance through navigation between BIC and PT-symmetric phase transition exceptional point. In particular, we demonstrate a fully symmetric Fano resonance in a system of two coupled bright and dark mode resonators. This result goes beyond current wisdom on this topic and demonstrates the universality of scattering matrix eigenfrequency solutions highlighted in our study. The validity of our approach is corroborated through comparison with experimental and full 3D numerical simulations results published in the literature making it thus possible to grasp a large body of experimental work carried out in this field. The detrimental impact of absorption losses on the contrast of the Fano resonance, which must be two orders of magnitude lower than the radiative losses, is also evidenced.

Directed Evolution of 4-Hydroxyphenylpyruvate Biosensors Based on a Dual Selection System.

Biosensors based on allosteric transcription factors have been widely used in synthetic biology. In this study, we utilized the Acinetobacter ADP1 transcription factor PobR to develop a biosensor activating the PpobA promoter when bound to its natural ligand, 4-hydroxybenzoic acid (4HB). To screen for PobR mutants responsive to 4-hydroxyphenylpyruvate(HPP), we developed a dual selection system in E. coli. The positive selection of this system was used to enrich PobR mutants that identified the required ligands. The following negative selection eliminated or weakened PobR mutants that still responded to 4HB. Directed evolution of the PobR library resulted in a variant where PobRW177R was 5.1 times more reactive to 4-hydroxyphenylpyruvate than PobRWT. Overall, we developed an efficient dual selection system for directed evolution of biosensors.

High-performance multi-parameter fiber sensor by grating-enhanced Mach-Zehnder interference.

A multi-parameter dual-core fiber sensor is proposed to realize highly sensitive detection of illumination, temperature, and humidity, separately. Through partial grating etching of a one-side core, the interaction between the core and the external environment is enhanced. Then, combining the Mach-Zehnder effect of the dual core, a higher sensing sensitivity is obtained. Experimental results show the temperature sensitivity is higher than 6.1952 nm/°C. Besides, the humidity and illumination resolution can reach as accurate as 0.041 relative humidity (RH) and 0.025 light units, respectively. To have better multi-parameter sensing and demodulation, the deep learning algorithm of a one-dimensional convolutional neural network (1D-CNN) is used to reach an accuracy of 99.05% with ∼2.00 root mean square error (RMSE). We envision such an excellent multi-parameter sensor can be promising in environmental monitoring and intelligent manufacturing.

Directed evolution of the PobR allosteric transcription factor to generate a biosensor for 4-hydroxymandelic acid.

Hydroxy-mandelic acid (HMA) is widely applied in pharmaceuticals, food and cosmetics. In this study, we aimed to develop an allosteric transcription factors (aTFs) based biosensor for HMA. PobR, an aTF for HMA analog 4-hydroxybenzoic acid, was used to alter its selectivity and create novel aTFs responsive to HMA by directed evolution. We established a PobR mutant library with a capacity of 550,000 mutants using error-prone PCR and Megawhop PCR. Through our screening, two mutants were obtained with responsiveness to HMA. Analysis of each missense mutation indicating residues 122-126 were involved in its PobR ligand specificity. These results showed the effectiveness of directed evolution in switching the ligand specificity of a biosensor and improving HMA production.

Analysis of Differentially Expressed Genes of Chrysoperla sinica Related to Flight Capacity by Transcriptome.

The lacewing Chrysoperla sinica (Tjeder) is a common natural enemy of many insect pests in China and is frequently employed for biological control programs. Adults make migratory flights after emergence, which reduces their effectiveness as biological control agents. Previously, we proved that 2-d-old unmated females exhibited significantly stronger flight ability than 3-d-old ones. Meanwhile, 3-d-old unmated adults flew significantly longer distances than mated ones. In this study, Illumina RNA sequencing was performed to characterize differentially expressed genes (DEGs) between virgin and mated adults of different ages in a single female strain of C. sinica. In total, 713,563,726 clean reads were obtained and de novo assembled into 109,165 unigenes with an average length of 847 bp (N50 of 1,754 bp), among which 4,382 (4.01%) unigenes matched known proteins. Based on these annotations, many putative transcripts were related to C. sinica's flight capacity and muscle structure, energy supply, growth, development, environmental adaptability, and metabolism of nutritional components and bioactive components. In addition, the differential expression of transcripts between different ages and mating status were analyzed, and DEGs participating in flight capacity and muscles were detected, including glutathione hydrolase, NAD-specific glutamate dehydrogenase, aminopeptidase, and acidic amino acid decarboxylase. The DEGs with functions associated with flight capacity and muscles exhibited higher transcript levels for younger (2 d--old) virgins. This comprehensive C. sinica transcriptomic data provide a foundation for a better understanding of the molecular mechanisms underlying the flight capacity to meet the physiological demands of flight muscles in C. sinica.

Broadband Filter and Adjustable Extinction Ratio Modulator Based on Metal-Graphene Hybrid Metamaterials.

A novel multifunctional device based on a hybrid metal-graphene Electromagnetically induced transparency (EIT) metamaterial at the terahertz band is proposed. It is composed of a parallel cut wire pair (PCWP) that serves as a dark mode resonator, a vertical cut wire pair (VCWP) that serves as a bright mode resonator and a graphene ribbon that serves as a modulator. An ultra-broadband transmission window with 1.23 THz bandwidth can be obtained. The spectral extinction ratio can be tuned from 26% to 98% by changing the Fermi level of the graphene. Compared with previous work, our work has superior performance in the adjustable bandwidth of the transmission window without changing the structure of the dark and bright mode resonators, and has a high extinction ratio and dynamic adjustability. Besides, we present the specific application of the device in filters and optical modules. Therefore, we believe that such a metamaterial structure provides a new way to actively control EIT-like, which has promising applications in broadband optical filters and photoelectric intensity modulators in terahertz communications.

A Thermal Tuning Meta-Duplex-Lens (MDL): Design and Characterization.

Multifunctional metasurfaces play an important role in the development of integrated optical paths. However, some of the realizations of current multifunctional metasurface devices depend on polarization selectivity, and others change the polarization state of the outgoing light. Here, based on vanadium dioxide (VO2) phase change material, a strategy to design a meta-duplex-lens (MDL) is proposed and numerical simulation calculations demonstrate that at low temperature (about 300 K), VO2 behaves as a dielectric so that the MDL can act as a transmission lens (transmission efficiency of 87.6%). Conversely, when VO2 enters the metallic state (about 355 K), the MDL has the ability to reflect and polymerize electromagnetic waves and works as a reflection lens (reflection efficiency of 85.1%). The dielectric waveguide and gap-surface plasmon (GSP) theories are used in transmission and reflection directions, respectively. In order to satisfy the coverage of the phase gradient in the range of 2π in both cases, we set the antenna as a nanopillar with a high aspect ratio. It is notable that, via symmetrical antennas acting in concert with VO2 phase change material, the polarization states of both the incident light and the outgoing light are not changed. This reversible tuning will play a significant role in the fields of imaging, optical storage devices, communication, sensors, etc.

Efficient point-by-point manipulated visible meta-vortex-lenses with arbitrary orbital angular momentum.

The ability of light to carry and deliver orbital angular momentum (OAM) in the form of optical vortices has attracted much interest. Conventional optical vortices are usually generated by bulky or expensive devices, which would sharply decrease the integration of optical communication systems. Here we demonstrate efficient large-area wavelength-thick metasurfaces that have the ability to produce high-quality optical vortexes with arbitrary OAM and to focus the beams into wavelength-scale rings with efficiency as high as 80%. Moreover, we reveal the relationship between size and energy distribution of focal rings (FR) with different OAMs: as the number of OAM increases, the size of the FR is linearly increasing, the peak focusing intensity (FFI) is decreasing in inverse proportional type, while the total energy on the FR remain almost unchanged. Rigorous quantitative analysis about the coupling effect among nanoantennas and the chromatic aberrations of the proposed metasurfaces are further discussed. We envision such highly efficient metasurfaces for spiral focusing will have potential applications in optical tweezers and communications.

Identification of lipid-like salicylic acid-based derivatives as potent and membrane-permeable PTP1B inhibitors.

Developing protein tyrosine phosphatase-1B (PTP1B) inhibitors is an important strategy to treat type 2 diabetes mellitus (T2DM). Most existing ionic PTP1B inhibitors aren't of clinical useful due to their low cell-permeability, however. Herein, we introduced a series of lipid-like acid-based (salicylic acid) modules to prepare PTP1B inhibitors, and demonstrated a marked improvement of cell-permeability while maintaining excellent PTP1B inhibitory activity (e.g. compound B12D, IC50 = 0.37 µM against PTP1B and Papp = 1.5 × 10-6 cm/s). We believe that this strategy can be widely utilized to modify potent lead compounds with low cell-permeability.

Discovery of 2-ethoxy-4-(methoxymethyl)benzamide derivatives as potent and selective PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin signaling, is considered as a promising and validated therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. Upon careful study, a series of 2-ethoxy-4-(methoxymethyl)benzamide and 2-ethoxy-5-(methoxymethyl)benzamide analogs designed by the "bioisosteric principle" were discovered, wherein their PTP1B inhibitory potency, type of PTP1B inhibition, selectivity and membrane permeability were evaluated. Among them, compound 10m exhibited high inhibitory activity (IC50 = 0.07 µM), significant selectivity (32-fold) over T-cell PTPase (TCPTP) as well as good membrane permeability (Papp = 2.41 × 10-6 cm/s). Further studies on cell viability and cellular activity revealed that compound 10m could enhance insulin-stimulated glucose uptake with no significant cytotoxicity.

Dynamically Temperature-Voltage Controlled Multifunctional Device Based on VO2 and Graphene Hybrid Metamaterials: Perfect Absorber and Highly Efficient Polarization Converter.

Vanadium dioxide (VO2) is a temperature phase change material that has metallic properties at high temperatures and insulation properties at room temperature. In this article, a novel device has been designed based on the dielectric metasurface consisting of VO2 and graphene array, which can achieve multiple functions by adjusting temperature and voltage. When the temperature is high (340 K), the device is in the absorption state and its absorptivity can be dynamically controlled by changing the temperature. On the other hand, the device is in the polarization state under room temperature, and the polarization of electromagnetic waves can be dynamically controlled by adjusting the voltage of graphene. This device can achieve a broadband absorber (the maximum absorptance reaches 99.415% at wavelengths ranging from 44 THz to 52 THz) and high polarization conversion efficiency (>99.89%) in the mid-infrared range, which has great advantages over other single-function devices. Our results demonstrate that this multifunctional device may have widespread applications in emitters, sensors, spatial light modulators, IR camouflages, and can be used in thermophotovoltaics and wireless communication.

The Delivery of a Wnt Pathway Inhibitor Toward CSCs Requires Stable Liposome Encapsulation and Delayed Drug Release in Tumor Tissues.

The Wnt signaling pathway is involved in tumorigenesis and various stages of tumor progression, including the epithelial-mesenchymal transition, metastasis, and drug resistance. Many efforts have been made to develop drugs targeting this pathway. CGX1321 is a porcupine inhibitor that can effectively block Wnt ligand synthesis and is currently undergoing clinical trials. However, drugs targeting the Wnt pathway may frequently cause adverse events in normal tissues, such as the intestine and skin. Formulation of the drug inside liposomes could enable preferential drug delivery to solid tumor tissues and limit drug exposure in normal organs. We developed a strategy to stably encapsulate CGX1321 inside liposomes with minimal drug releases in circulation. The liposomal drugs were shown to interfere with the aberrant Wnt signaling specifically in tumor tissues, resulting in focused effects on LGR5+ CSCs (cancer stem cells), while sparing other cells from significant cytotoxicity. We showed it is feasible to use such a CSC elimination approach to treat malignant cancers prone to rapid progression using a LoVo tumor model as well as a GA007 patient derived xenograft (PDX) model. Nano drug delivery systems may be required for precision medicine in cancer therapy.

Multi-functional double rare-earth-doped ball sensor based on a hollow-core microstructure fiber.

In this Letter, we demonstrated an ∞-type multi-functional sensor through splicing double rare-earth-doped balls (REDBs) with a hollow-core microstructure fiber. Utilizing the different thermal expansion and thermo-optic coefficients of silica and rare earth, the interference of REDBs will be more sensitive to temperature. On both ends of the dual-ball, we spliced the anti-resonance fiber (ARF) to satisfy the broad waveband transmission. In addition, the special anti-resonance loss peak of the ARF can make the amplitude change of the signal more obvious. The experiments prove that a multi-functional sensor is capable of detecting versatile parameters, such as the illumination response, liquid concentration, and ambient temperature. In addition, the temperature sensitivity can reach 1 nm/°C, and the illumination response is obvious. We also analyze the concentration of P-Methylthiophenol, a substance harmful to human beings in the environment. Its resolution can reach 3.125E-5 mol/L. These results indicate that the sensor can be used in underground mine detection, environmental monitoring, and so on.

Dynamically Tunable Resonant Strength in Electromagnetically Induced Transparency (EIT) Analogue by Hybrid Metal-Graphene Metamaterials.

In this paper, a novel method to realize a dynamically tunable analogue of EIT for the resonance strength rather than the resonance frequency is proposed in the terahertz spectrum. The introduced method is composed of a metal EIT-like structure, in which a distinct EIT phenomenon resulting from the near field coupling between bright and dark mode resonators can be obtained, as well as an integrated monolayer graphene ribbon under the dark mode resonator that can continuously adjust the resonance strength of transparency peak by changing the Fermi level of the graphene. Comparing structures that need to be modulated individually for each unit cell of the metamaterials, the proposed modulation mechanism was convenient for achieving synchronous operations for all unit cells. This work demonstrates a new platform of modulating the EIT analogue and paves the way to design terahertz functional devices which meet the needs of optical networks and terahertz communications.

Investigation of stereoisomeric bisarylethenesulfonic acid esters for discovering potent and selective PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) has been considered as a promising therapeutic target for type 2 diabetes mellitus (T2DM) and obesity due to its key regulating effects in insulin signaling and leptin receptor pathways. In this work, a series of cis- and trans-pyrrolidine bisarylethenesulfonic acid esters were prepared and their PTP1B inhibitory potency, selectivity and membrane permeability were evaluated. These novel stereoisomeric molecules especially trans-isomers exhibited remarkable inhibitory activity, significant selectivity as well as good membrane permeability (e.g. compound 28a, IC50 = 120, 1940 and 2670 nM against PTP1B, TCPTP and SHP2 respectively, and Papp = 1.74 × 10-6 cm/s). Molecular simulations indicated that trans-pyrrolidine bisarylethenesulfonic acid esters yielded the stronger binding affinity than their cis-isomers by constructing more interactions with non-catalytic sites of PTP1B. Further biological activity studies revealed that compound 28a could enhance insulin-stimulated glucose uptake and insulin-mediated insulin receptor ß (IRß) phosphorylation with no significant cytotoxicity.

Smart nanoparticles assembled by endogenous molecules for siRNA delivery and cancer therapy via CD44 and EGFR dual-targeting.

We developed an anticancer siRNA delivery system (named HLPR) through modular assembly of endogenous molecules. The structure of HLPR was a tightly condensed siRNA-peptide inner core in turn surrounded by the disordered lipid layer and thin HA coating from which the EGFR-targeted amino acid sequences of YHWYGYTPQNVI partially protrude outside of cell surfaces. Both HA and YHWYGYTPQNVI anchored on HLPR were responsible for targeting CD44 and EGFR overexpressed on the tumor cell surfaces, respectively. HLPR was relatively stable in the blood circulation and reached the tumor tissue in vivo through passive and active targeting. Then HLPR entered tumor cells mainly through EGFR-mediated pathway followed by the separation of HA from the remaining parts of nanocomplexes. The HA-uncoated complexes escaped the endosome through the membrane fusion function of DOPE and released cargoes (siRNA and peptide/siRNA) in the cytoplasm. HLPR significantly inhibited the growth of implanted subcutaneous liver tumors without toxicity.

Metalenses Based on Symmetric Slab Waveguide and c-TiO2: Efficient Polarization-Insensitive Focusing at Visible Wavelengths.

A key goal of metalens research is to achieve wavefront shaping of light using optical elements with thicknesses on the order of the wavelength. Here we demonstrate ultrathin highly efficient crystalline titanium dioxide metalenses at blue, green, and red wavelengths (λ0 = 453 nm, 532 nm, and 633 nm, respectively) based on symmetric slab waveguide theory. These metalenses are less than 488 nm-thick and capable of focusing incident light into very symmetric diffraction-limited spots with strehl ratio and efficiency as high as 0.96 and 83%, respectively. Further quantitative characterizations about metalenses' peak focusing intensities and focal spot sizes show good agreement with theoretical calculation. Besides, the metalenses suffer only about 10% chromatic deviation from the ideal spots in visible spectrum. In contrast with Pancharatnam⁻Berry phase mechanism, which limit their incident light at circular polarization, the proposed method enables metalenses polarization-insensitive to incident light.

High-Efficiency, Near-Diffraction Limited, Dielectric Metasurface Lenses Based on Crystalline Titanium Dioxide at Visible Wavelengths.

Metasurfaces are planar optical elements that hold promise for overcoming the limitations of refractive and conventional diffractive optics. Previous metasurfaces have been limited to transparency windows at infrared wavelengths because of significant optical absorption and loss at visible wavelengths. Here we report a polarization-insensitive, high-contrast transmissive metasurface composed of crystalline titanium dioxide pillars in the form of metalens at the wavelength of 633 nm. The focal spots are as small as 0.54 λ d , which is very close to the optical diffraction limit of 0.5 λ d . The simulation focusing efficiency is up to 88.5%. A rigorous method for metalens design, the phase realization mechanism and the trade-off between high efficiency and small spot size (or large numerical aperture) are discussed. Besides, the metalenses can work well with an imaging point source up to ±15° off axis. The proposed design is relatively systematic and can be applied to various applications such as visible imaging, ranging and sensing systems.