Single-cell transcriptomes of kidneys in a 6-month-old boy with Denys-Drash syndrome reveal stromal cell heterogeneity in the tumor microenvironment.

Background: Denys-Drash syndrome (DDS) is a rare disease characterized with pseudohermaphroditism, nephroblastoma (also known as Wilms tumor), and diffuse mesangial sclerosis. The therapy for DDS is largely supportive, i.e. surgery and chemotherapy for Wilms tumor and renal replacement therapy. Due to the limited understanding of the pathogenesis, precision therapy for DDS is yet to be explored. We sought to explore the cellular components and interactions in kidney tissues from an infant with DDS. Methods: Whole-exome sequencing was performed to examine the mutations associated with DDS. Single-cell RNA sequencing (scRNA-seq) was performed to explore the heterogenicity of kidney tissue samples. Results: A 6-month-old infant with bilateral Wilms tumors and genital ambiguity was diagnosed as having DDS. Whole exome sequencing revealed a novel de novo mutation (p.F185fs*118) in exon 1 of WT1. scRNA-seq was performed in tissue samples from bilateral Wilms tumors and the normal kidney from this infant. Fibroblasts, myocytes, epithelial cells, endothelial cells, and mononuclear phagocytes (MPs) ranked at the top of the 31 135 total cells. Fibroblasts and myocytes were dominant in the Wilms tumor samples. In contrast, most epithelial cells and endothelial cells were found in normal kidney tissues. CD44 and TUBA1A were significantly changed in myocyte subclusters, which may contribute to chemotherapy drug resistance. Macrophages intensively interacted with cancerous cells, including fibroblasts, epithelial cells, and myocytes. Conclusions: A novel mutation (p.F185fs*118) in exon 1 of WT1 was identified in an infant with DDS. scRNA-Seq revealed the heterogenicity of cellular components in Wilms tumors and kidney tissues, shedding light on the pathogenesis of DDS.

Magneto-optical nonreciprocity without chirality: Archimedean spirals on InSb.

We report the observation of magneto-optical nonreciprocity in Faraday geometry in a hybrid metamaterial consisting of an Archimedean spiral metasurface and semiconductor InSb that serves as the magneto-optical medium. None of the metamaterial constituents possesses chirality, which is usually a necessary ingredient for optical nonreciprocity in natural materials when the light travels along the magnetic field direction. We also find that our metamaterial can serve as an optical element for polarization control via magnetic field. Another significant property of our hybrid metamaterial is the emergence of the four different transmittance states, which are observed for the four combinations of the positive and negative magnetic field and the direction of the wavevector of light.

Smilax glabra Roxb. flavonoids protect against pathological cardiac hypertrophy by inhibiting the Raf/MEK/ERK pathway: In vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb., the dry rhizome of Sarsaparilla, which is also known as Tu fuling (TFL) in China, is a well-known traditional CHINESE medicine that is widely used for detoxication, relieving dampness and as a diuretic. We have previously shown that the extracted TFL flavonoids (designated TFLF) possess anti-cardiac hypertrophy effects in vitro. However, the anti-cardiac hypertrophy effects of TFLF in vivo and the underlying mechanisms remain to be elucidated. AIM OF THE STUDY: To reveal the underlying therapeutic mechanism of TFLF on cardiac hypertrophy by using transverse aortic constriction (TAC) model and cellular assays in vitro. MATERIAL & METHODS: Cardiac hypertrophy was replicated by TAC surgery in rats or by isoprenaline treatment of rat H9C2 myocardial cells in vitro. Cardiac structure and function were evaluated by echocardiographic and hemodynamic examinations in vivo and histological analysis of tissues ex vivo. Biochemical kits and quantitative PCR were used to analyze markers of cardiac hypertrophy. Expression and phosphorylation of key proteins in the Raf/MEK/ERK pathway were quantified by Western blotting. We further confirmed our findings in H9C2 rat cardiomyocytes treated with isoprenaline and the ERK inhibitor in vitro. RESULTS: TFLF attenuated cardiac hypertrophy and fibrosis and improved cardiac dysfunction in TAC rats. TFLF treatment induced a strong reduction in serum NT-proBNP levels. Cardiac hypertrophy marker gene (ANP, BNP and ß-MHC) expression and the phosphorylation levels of c-Raf and ERK1/2 were decreased by TFLF treatment. TFLF also protected H9C2 cells from isoprenaline-induced hypertrophy in vitro via a similar molecular mechanism as that observed in the rat heart. Moreover, pretreatment with TRLF and the ERK inhibitor further inhibited the mRNA overexpression of hypertrophic genes in vitro. CONCLUSIONS: TFLFs may protect against pathological cardiac hypertrophy via negative regulation of the Raf/MEK/ERK pathway. Thus, TFLFs are implicated as a potential pharmacological agent for treating cardiac hypertrophy in clinical practice.

Nonreciprocal Fabry-Perot effect and performance enhancement in a magneto-optical InSb-based Faraday terahertz isolator.

The Faraday effect due to the cyclotron resonance of conduction electrons in semiconductor InSb allows for nonreciprocity of transmitted light in our Faraday THz isolator operating in the presence of a small magnetic field. We select InSb as an efficient medium for our isolator due to its high electron mobility, low electron effective mass, and narrow band gap. Experimental measurements of the isolator performance indicate a maximum achieved isolation power of 18.8 dB with an insertion loss of -12.6 dB. Our optical analysis of the device points to a remarkable nonreciprocal Fabry-Perot effect in the magneto-optical InSb layer as the origin of the multi-fold isolation enhancement. This nonreciprocity occurs as the Fabry-Perot reflections in the forward direction add constructively and enhance the transmittance at certain frequencies, while the Fabry-Perot reflections in the backward direction add destructively and suppress the transmittance at the same frequencies.

High-Efficiency and Wide-Angle Versatile Polarization Controller Based on Metagratings.

Metamaterials with their customized properties enable us to efficiently manipulate the polarization states of electromagnetic waves with flexible approaches, which is of great significance in various realms. However, most current metamaterial-based polarization controllers can only realize single function, which has extremely hindered the expansion of their applications. Here, we experimentally demonstrate highly efficient and multifunctional polarization conversion effects using metagrating by integrating single-structure metallic meta-atoms into the dielectric gratings. Benefiting from the combined advantages of the gratings and the metamaterials, the considered metagrating can operate in transmission and reflection modes simultaneously, acting as a high-performance and wide-angle quarter-wave or half-wave plate with distinct functions in different frequency bands. This metagrating structure is scalable to other frequency ranges and may provide opportunities to design compact multifunctional optical polarization control devices.

Fabry-Perot cavity resonance enabling highly polarization-sensitive double-layer gold grating.

We present experimental and theoretical investigations on the polarization properties of a single- and a double-layer gold (Au) grating, serving as a wire grid polarizer. Two layers of Au gratings form a cavity that effectively modulates the transmission and reflection of linearly polarized light. Theoretical calculations based on a transfer matrix method reveals that the double-layer Au grating structure creates an optical cavity exhibiting Fabry-Perot (FP) resonance modes. As compared to a single-layer grating, the FP cavity resonance modes of the double-layer grating significantly enhance the transmission of the transverse magnetic (TM) mode, while suppressing the transmission of the transverse electric (TE) mode. As a result, the extinction ratio of TM to TE transmission for the double-layer grating structure is improved by a factor of approximately 8 in the mid-wave infrared region of 3.4-6 µm. Furthermore, excellent infrared imagery is obtained with over a 600% increase in the ratio of the TM-output voltage (Vθ = 0°) to TE-output voltage (Vθ = 90°). This double-layer Au grating structure has great potential for use in polarimetric imaging applications due to its superior ability to resolve linear polarization signatures.

Metamaterial Perfect Absorber Analyzed by a Meta-cavity Model Consisting of Multilayer Metasurfaces.

We demonstrate that the metamaterial perfect absorber behaves as a meta-cavity bounded between a resonant metasurface and a metallic thin-film reflector. The perfect absorption is achieved by the Fabry-Perot cavity resonance via multiple reflections between the "quasi-open" boundary of resonator and the "close" boundary of reflector. The characteristic features including angle independence, ultra-thin thickness and strong field localization can be well explained by this meta-cavity model. With this model, metamaterial perfect absorber can be redefined as a meta-cavity exhibiting high Q-factor, strong field enhancement and extremely high photonic density of states, thereby promising novel applications for high performance sensor, infrared photodetector and cavity quantum electrodynamics devices.

Broadband angle- and permittivity-insensitive nondispersive optical activity based on planar chiral metamaterials.

Because of the strong inherent resonances, the giant optical activity obtained via chiral metamaterials generally suffers from high dispersion, which has been a big stumbling block to broadband applications. In this paper, we propose a type of planar chiral metamaterial consisting of interconnected metal helix slat structures with four-fold symmetry, which exhibits nonresonant Drude-like response and can therefore avoid the highly dispersive optical activity resulting from resonances. It shows that the well-designed chiral metamaterial can achieve nondispersive and pure optical activity with high transmittance in a broadband frequency range. And the optical activity of multi-layer chiral metamaterials is proportional to the layer numbers of single-layer chiral metamaterial. Most remarkably, the broadband behaviors of nondispersive optical activity and high transmission are insensitive to the incident angles of electromagnetic waves and permittivity of dielectric substrate, thereby enabling more flexibility in polarization manipulation.

Giant THz surface plasmon polariton induced by high-index dielectric metasurface.

We use computational approaches to explore the role of a high-refractive-index dielectric TiO2 grating with deep subwavelength thickness on InSb as a tunable coupler for THz surface plasmons. We find a series of resonances as the grating couples a normally-incident THz wave to standing surface plasmon waves on both thin and thick InSb layers. In a marked contrast with previously-explored metallic gratings, we observe the emergence of a much stronger additional resonance. The mechanism of this giant plasmonic resonance is well interpreted by the dispersion of surface plasmon excited in the air\TiO2\InSb trilayer system. We demonstrate that both the frequency and the intensity of the giant resonance can be tuned by varying dielectric grating parameters, providing more flexible tunability than metallic gratings. The phase and amplitude of the normally-incident THz wave are spatially modulated by the dielectric grating to optimize the surface plasmon excitation. The giant surface plasmon resonance gives rise to strong enhancement of the electric field above the grating structure, which can be useful in sensing and spectroscopy applications.

A Low-loss Metasurface Antireflection Coating on Dispersive Surface Plasmon Structure.

Over the years, there has been increasing interest in the integration of metal hole array (MHA) with optoelectronic devices, as a result of enhanced coupling of incident light into the active layer of devices via surface plasmon polariton (SPP) resonances. However, not all incident light contributes to the SPP resonances due to significant reflection loss at the interface between incident medium and MHA. Conventional thin-film antireflection (AR) coating typically does not work well due to non-existing material satisfying the AR condition with strong dispersion of MHA's effective impedances. We demonstrate a single-layer metasurface AR coating that completely eliminates the refection and significantly increases the transmission at the SPP resonances. Operating at off-resonance wavelengths, the metasurface exhibits extremely low loss and does not show resonant coupling with the MHA layer. The SPP resonance wavelengths of MHA layer are unaffected whereas the surface wave is significantly increased, thereby paving the way for improved performance of optoelectronic devices. With an improved retrieval method, the metasurface is proved to exhibit a high effective permittivity () and extremely low loss (tan δ ~ 0.005). A classical thin-film AR coating mechanism is identified through analytical derivations and numerical simulations.

Thin InSb layers with metallic gratings: a novel platform for spectrally-selective THz plasmonic sensing.

We present a computational study of terahertz optical properties of a grating-coupled plasmonic structure based on micrometer-thin InSb layers. We find two strong absorption resonances that we interpret as standing surface plasmon modes and investigate their dispersion relations, dependence on InSb thickness, and the spatial distribution of the electric field. The observed surface plasmon modes are well described by a simple theory of the air/InSb/air tri-layer. The plasmonic response of the grating/InSb structure is highly sensitive to the dielectric environment and the presence of an analyte (e.g., lactose) at the InSb interface, which is promising for terahertz plasmonic sensor applications. We determine the sensor sensitivity to be 7200 nm per refractive index unit (or 0.06 THz per refractive index unit). The lower surface plasmon mode also exhibits a splitting when tuned in resonance with the vibrational mode of lactose at 1.37 THz. We propose that such interaction between surface plasmon and vibrational modes can be used as the basis for a new sensing modality that allows the detection of terahertz vibrational fingerprints of an analyte.

A facile and mild synthesis of trisubstituted allylic sulfones from Morita-Baylis-Hillman carbonates.

An efficient and catalyst-free synthesis of trisubstituted allylic sulfones through an allylic sulfonylation reaction of Morita-Baylis-Hillman (MBH) carbonates with sodium sulfinates has been developed. Under the optimized reaction conditions, a series of trisubstituted allylic sulfones were rapidly prepared in good to excellent yields (71%-99%) with good to high selectivity (Z/E from 79:21 to >99:1). Compared with known synthetic methods, the current protocol features mild reaction temperature, high efficiency and easily available reagents.

Enhanced transmission due to antireflection coating layer at surface plasmon resonance wavelengths.

We present experiments and analysis on enhanced transmission due to dielectric layer deposited on a metal film perforated with two-dimensional periodic array of subwavelength holes. The Si3N4 overlayer is applied on the perforated gold film (PGF) fabricated on GaAs substrate in order to boost the transmission of light at the surface plasmon polariton (SPP) resonance wavelengths in the mid- and long-wave IR regions, which is used as the antireflection (AR) coating layer between two dissimilar media (air and PGF/GaAs). It is experimentally shown that the transmission through the perforated gold film with 1.8 µm (2.0 µm) pitch at the first-order (second-order) SPP resonance wavelengths can be increased up to 83% (110%) by using a 750 nm (550 nm) thick Si3N4 layer. The SPP resonance leads to a dispersive resonant effective permeability (µeff ≠ 1) and thereby the refractive index matching condition for the conventional AR coating on the surface of a dielectric material cannot be applied to the resonant PGF structure. We develop and demonstrate the concept of AR condition based on the effective parameters of PGF. In addition, the maximum transmission (zero reflection) condition is analyzed numerically by using a three-layer model and a transfer matrix method is employed to determine the total reflection and transmission. The numerically calculated total reflection agrees very well with the reflection obtained by 3D full electromagnetic simulations of the entire structure. Destructive interference conditions for amplitude and phase to get zero reflection are well satisfied.

Analysis of subwavelength metal hole array structure for the enhancement of back-illuminated quantum dot infrared photodetectors.

This paper is focused on analyzing the impact of a two-dimensional metal hole array structure integrated to the back-illuminated quantum dots-in-a-well (DWELL) infrared photodetectors. The metal hole array consisting of subwavelength-circular holes penetrating gold layer (2D-Au-CHA) provides the enhanced responsivity of DWELL infrared photodetector at certain wavelengths. The performance of 2D-Au-CHA is investigated by calculating the absorption of active layer in the DWELL structure using a finite integration technique. Simulation results show that the performance of the DWELL focal plane array (FPA) is improved by enhancing the coupling to active layer via local field engineering resulting from a surface plasmon polariton mode and a guided Fabry-Perot mode. Simulation method accomplished in this paper provides a generalized approach to optimize the design of any type of couplers integrated to infrared photodetectors. Experimental results demonstrate the enhanced signal-to-noise ratio by the 2D-Au-CHA integrated FPA as compared to the DWELL FPA. A comparison between the experiment and the simulation shows a good agreement.

Photoinduced handedness switching in terahertz chiral metamolecules.

Switching the handedness, or the chirality, of a molecule is of great importance in chemistry and biology, as molecules of different handedness exhibit dramatically different physiological properties and pharmacological effects. Here we experimentally demonstrate handedness switching in metamaterials, a new class of custom-designed composites with deep subwavelength building blocks, in response to external optical stimuli. The metamolecule monolayer flips the ellipticity and rotates the polarization angle of light in excess of 10° under optical excitation, a much stronger electromagnetic effect than that of naturally available molecules. Furthermore, the experimentally demonstrated optical switching effect does not require a structural reconfiguration, which is typically involved in molecular chirality switching and is inherently slow. The handedness switching in chiral metamolecules allows electromagnetic control of the polarization of light and will find important applications in manipulation of terahertz waves, such as dynamically tunable terahertz circular polarizers and polarization modulators for terahertz radiations.

Tailored resonator coupling for modifying the terahertz metamaterial response.

We experimentally and numerically study the nature of coupling between laterally paired terahertz metamaterial split-ring resonators. Coupling is shown to modify the inductive-capacitive (LC) resonances resulting in either red or blue-shifting. Results indicate that tuning of the electric and magnetic coupling parameters may be accomplished not by changing the orientation or density of SRRs, but by a design modification at the unit cell level. These experiments illustrate additional degrees of freedom in tuning the electromagnetic response, which offers a path to more robust metamaterial designs.

Dirac dynamics in one-dimensional graphene-like plasmonic crystals: pseudo-spin, chirality, and diffraction anomaly.

We introduce a new class of plasmonic crystals possessing graphene-like internal symmetries and Dirac-type spectrum in k-space. We study dynamics of surface plasmon polaritons supported in the plasmonic crystals by employing the formalism of Dirac dynamics for relativistic quantum particles. Through an analogy with graphene, we introduce a concept of pseudo-spin and chirality to indicate built-in symmetry of the plasmonic crystals near Dirac point. The surface plasmon polaritons with different pseudo-spin states are shown to split in the crystals into two beams, analogous to spin Hall effect.

Antireflection coating using metamaterials and identification of its mechanism.

We present a novel approach of antireflection coating using metamaterials. It dramatically reduces the reflection and greatly enhances the transmission near a specifically designed frequency over a wide range of incidence angles for both transverse magnetic and transverse electric polarizations. A classical interference mechanism is identified through analytical derivations and numerical simulations. It elucidates that the tailored magnitude and phase of waves reflected and transmitted at boundaries of metamaterial coating are responsible for the antireflection.

Coupling effect between two adjacent chiral structure layers.

A pair of mutually twisted metallic cross-wires can produce giant optical activity. When this single chiral layer is stacked layer by layer in order to build a thick chiral metamaterial, strong coupling effects are found between the two adjacent chiral layers. We studied these coupling effects numerically and experimentally. The results show that the existing coupling between chiral layers can make the chiral properties of a two-layered chiral metamaterial different from the constituting single chiral layers. It is explained qualitatively that the coupling effects are generated from the coupling of metallic cross-wires belonging to different chiral layers. Our experimental results are in good agreement with the simulation results.

Bi-layer cross chiral structure with strong optical activity and negative refractive index.

The properties of periodic pairs of mutually twisted metallic (silver) crosses separated by dielectric layer have been investigated by numerical simulation. The results show that the exceptionally strong polarization rotation and circular dichroism, negative permeability and negative refractive index are found at the infrared communication wavelength (1.55 microm).