Vertical directional coupling based grating emission engineering for optical phased arrays.

In this Letter, a novel, to the best of our knowledge, vertical directional coupling waveguide grating (VDCWG) architecture is proposed to increase the length of waveguide grating antennas for large aperture on-chip optical phased arrays (OPAs). In this new architecture, the grating emission strength is engineered by the vertical directional coupler, which provides additional degrees of design freedom. Theoretical analysis and numerical simulation show that the VDCWG can adjust the grating strength in the range of more than two orders of magnitude, corresponding to an effective grating length more than a centimeter. For proof-of-concept, a VDCWG antenna with a length of 1.5 mm is experimentally demonstrated. The grating strength is measured to be 0.17 mm-1, and the far-field divergence angle is 0.061°. A 16-channel OPA is also developed based on the proposed VDCWG, which proves the potential of the new architecture for large aperture OPAs.

Ultralong waveguide grating antenna enabled by evanescent field modulation.

Waveguide grating antenna (WGA) is a key component for an on-chip optical phased array. In order to form a beam with a small divergence angle, WGAs of several millimeters in length are highly desired. However, in high-index-contrast platforms such as silicon-on-insulator (SOI), such long WGAs typically require weakly modulated gratings with critical feature sizes below 10 nm. In this paper, we experimentally demonstrate a new, to the best of our knowledge, strategy to implement long WGAs. Instead of directly modulating a waveguide, we propose periodically modulating the evanescent field with subwavelength blocks. With this arrangement, weak grating strength can be achieved while maintaining a minimum feature size as large as 100 nm. For proof-of-concept, we experimentally demonstrate a 1-mm-long, single-etched WGA on a conventional 220 nm SOI platform, which achieves a far-field divergence angle of 0.095° and a wavelength scanning sensitivity of 0.168°/nm.

Subwavelength structure enabled ultra-long waveguide grating antenna.

Because of the high index contrast, current silicon photonics based optical phased arrays cannot achieve small beam divergence and large field-of-view simultaneously without increasing fabrication complexity. To resolve the dilemma, we propose an ultra-long waveguide grating antenna formed by placing subwavelength segments within the evanescent field of a conventional strip waveguide. Bound state in the continuum effect is leveraged to suppress the sidewall emission. As a proof of concept, we theoretically demonstrated a millimeter-long through-etched waveguide grating antenna with a divergence angle of 0.081° and a feature size compatible with current silicon photonics foundries.

Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen.

BACKGROUND: The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation. METHODS: Using unique brown adipocyte-specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice. RESULTS: We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte-selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor-dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT. CONCLUSIONS: These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.

Brown Adipocyte-Specific PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deletion Impairs Perivascular Adipose Tissue Development and Enhances Atherosclerosis in Mice.

Objective- Perivascular adipose tissue (PVAT) contributes to vascular homeostasis by producing paracrine factors. Previously, we reported that selective deletion of PPARγ (peroxisome proliferator-activated receptor γ) in vascular smooth muscle cells resulted in concurrent loss of PVAT and enhanced atherosclerosis in mice. To address the causal relationship between loss of PVAT and atherosclerosis, we used BA-PPARγ-KO (brown adipocyte-specific PPARγ knockout) mice. Approach and Results- Deletion of PPARγ in brown adipocytes did not affect PPARγ in white adipocytes or vascular smooth muscle cells or PPARα and PPARδ expression in brown adipocytes. However, development of PVAT and interscapular brown adipose tissue was remarkably impaired, associated with reduced expression of genes encoding lipogenic enzymes in the BA-PPARγ-KO mice. Thermogenesis in brown adipose tissue was significantly impaired with reduced expression of thermogenesis genes in brown adipose tissue and compensatory increase in subcutaneous and gonadal white adipose tissues. Remarkably, basal expression of inflammatory genes and macrophage infiltration in PVAT and brown adipose tissue were significantly increased in the BA-PPARγ-KO mice. BA-PPARγ-KO mice were crossbred with ApoE KO (apolipoprotein E knockout) mice to investigate the development of atherosclerosis. Flow cytometry analysis confirmed increased systemic and PVAT inflammation. Consequently, atherosclerotic lesions were significantly increased in mice with impaired PVAT development, thus indicating that the lack of normal PVAT is sufficient to drive increased atherosclerosis. Conclusions- PPARγ is required for functional PVAT development. PPARγ deficiency in PVAT, while still expressed in vascular smooth muscle cell, enhances atherosclerosis and results in vascular and systemic inflammation, providing new insights on the specific roles of PVAT in atherosclerosis and cardiovascular disease at large.

MitoNEET in Perivascular Adipose Tissue Prevents Arterial Stiffness in Aging Mice.

PURPOSE: Arterial stiffness is an inevitable consequence of the aging process and is considered an early stage in the development of cardiovascular diseases. The perivascular adipose tissue (PVAT) is a distinct functional integral layer of the vasculature actively involved in blood pressure regulation and atherosclerosis development via PVAT-derived paracrine/autocrine factors. However, there is little knowledge regarding the relationship between PVAT and arterial stiffness. METHODS: Using unique mice lacking PVAT, high-fat diet-induced obesity, and in mice overexpressing brown adipocyte selective mitoNEET, we investigated the relationship between PVAT and arterial stiffness in mice. RESULTS: We found that lack of PVAT enhanced arterial stiffness in aging mice. High-fat diet feeding of aging C57BL/6J wild-type mice significantly induced hypertrophic PVAT and enhanced arterial stiffness. Furthermore, the expression of mitoNEET, a mitochondrial membrane protein related to energy expenditure, was significantly increased by pioglitazone treatment, while reduced in the hypertrophic PVAT induced by high-fat diet. Overexpression of mitoNEET in PVAT reduced the expression of inflammatory genes and was associated with lower pulse wave velocity in aging mice. CONCLUSIONS: These data indicate that local PVAT homeostasis especially inflammation in PVAT is associated with arterial stiffness development. Pioglitazone-induced mitoNEET in PVAT prevents PVAT inflammation and is negatively associated with arterial stiffness. These findings provide new experimental insight into the roles of pioglitazone on PVAT in arterial stiffness and indicate that PVAT might be a target to treat or prevent cardiovascular disease.

Improving the spatial resolution of volume Bragg grating two-dimensional monochromatic images.

Higher spatial resolution indicates sharper recognition ability in applications. To improve the spatial resolution of volume Bragg grating spectral imagers, quantitative wave vector theory is used to elucidate the formation mechanism of diffraction blur, and the corresponding optimal design approaches are put forward. The simulation results show that the main factors for the spectral image blur are the chromatic blur and diffraction aberration, while the central wavelength deviation further deteriorates these. To deal with these factors, one must optimize the grating period, thickness, slant angle, and refractive index, as well as compress the divergence angle of the incident beam. After optimization under the guidance of the newly defined integrated merit functions, the experimental results show that the optimized smeared point-spread function is reduced by about an order of magnitude. The horizontal spatial resolution of the recorded two-dimensional monochromatic images is improved to 14.3 lines/mm under diffuse reflection illumination.

Femtogram scale high frequency nano-optomechanical resonators in water.

A femtogram scale nanobeam optomechanical crystal (OMC) resonator operating in water is designed and demonstrated. After immersing the device in water, the mechanical Q-factor reduces to 6.6 from 2285 in air. The thermomechanical motion of the highly damped mechanical resonance in water can be resolved using the sensitive cavity optomechanical readout. The mechanical frequency is shifted to 5.251 GHz from 5.3 GHz in air due to the added motional inertia. From the thermomechanical noise spectrum of the mechanical resonance, a noise floor of 9.33am/Hz is achieved in water. Through 2D finite element method (FEM) simulations, the acoustic dissipation dominates the low mechanical Q-factor of the device during the interaction between the mechanical resonance and surrounding water. The mass sensitivity of the present device is estimated to be 1.33ag/Hz in water.

Two-mode contra-directional coupler based on superposed grating.

We propose and demonstrate a novel two-mode grating assisted contra-directional coupler (TGACC), which is capable of filtering two modes channels simultaneously by superposed grating with two superposed grating components. Finite-difference time-domain simulation is employed to study the structure. The influences of main structural parameters are analyzed, and apodization is employed to reduce the band sidelobes, crosstalk and back-reflections. We experimentally present a mode-channel switchable TGACC for 2.54nm-wide wavelength band centered at 1548.0nm by 50K thermal-optic tuning. With two channels combined into one device, the TGACC can help to enrich the functionality and reduce the footprint of mode-division multiplexing (MDM) systems.

Design of a femtogram scale double-slot photonic crystal optomechanical cavity.

We present the design of a double-slot photonic crystal cavity as an optomechanical device which contains a nanomechanical resonator with an effective mass as small as 6.91 fg. The optical Q-factor is optimized to 2 × 10(5). Using phononic crystals, the mechanical vibration is confined in a small volume to form a mechanical mode of 4 GHz with a high mechanical Q-factor and a femtogram effective mass. The localized mechanical mode overlaps with the optical field and strengthens the optomechanical coupling with a vacuum optomechanical coupling rate g0/2π exceeding 600 kHz. Considering fabrication imperfections, structures with deviation from ideal design are studied. The symmetry breakage of the structures and the displacement fields makes the mechanical effective masses reduced and close to 4 fg. The devices can be used in ultrasensitive sensing of mass, force and displacement.

Proteomic and immunological identification of two new allergens from silkworm (Bombyx mori L.) pupae.

This study explored food allergy caused by eating silkworm (Bombyx mori L.) pupae, a traditionally accepted food and animal feed in East and Southeast Asia, and identified two new allergens by proteomic and immunological methods. Proteins isolated from silkworm pupae were separated by two-dimensional gel electrophoresis (2-DE); pooled sera from patients allergic to silkworm pupa proteins were used to detect immunoglobulin E (IgE)-binding proteins by western blotting, and allergens specific for silkworm pupa consumption-caused allergy were visualised with the ECL reagents. The selected allergen proteins were further identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) analysis. Finally, chitinase and paramyosin were identified as silkworm pupa proteins showing strong immunoglobulin (IgE)-binding reaction. Analysis of the sequence homology of the two proteins using the AllergenOnline database indicated that chitinase and paramyosin shared 24.8% and 62.8% sequence homology with known allergens Der f 18 (Dermatophagoides farinae) and Der p 11 (Dermatophagoides pteronyssinus), respectively. Our results shed light on the understanding and treatment of silkworm pupa allergy.

Genome-wide CNV analysis in mouse induced pluripotent stem cells reveals dosage effect of pluripotent factors on genome integrity.

BACKGROUND: Induced pluripotent stem cells (iPSCs) derived from somatic cells have enormous potential for clinical applications. Notably, it was recently reported that reprogramming from somatic cells to iPSCs can induce genomic copy number variation (CNV), which is one of the major genetic causes of human diseases. However it was unclear if this genome instability is dependent on reprogramming methods and/or the genetic background of donor cells. Furthermore, genome-wide CNV analysis is technically challenging and CNV data need to be interpreted with care. RESULTS: In order to carefully investigate the possible CNV instability during somatic reprogramming, we performed genome-wide CNV analyses with 41 mouse iPSC lines generated from the same parental donor; therefore, the donor's genetic background can be controlled. Different reprogramming factor combinations and dosages were used for investigating potential method-dependent effects on genome integrity. We detected 63 iPSC CNVs using high-resolution comparative genomic hybridization. Intriguingly, CNV rates were negatively associated with the dosages of classic factor(s). Furthermore, the use of high-performance engineered factors led to less CNVs than the classic factor(s) of the same dosage. CONCLUSION: Our observations suggest that sufficient reprogramming force can protect the genome from CNV instability during the reprogramming process.

Enhanced light emission from Ge quantum dots in photonic crystal ring resonator.

Light emitter based on Ge quantum dots embedded in photonic crystal ring resonator is designed and fabricated. Six sharp resonant peaks dominate the photoluminescence (PL) spectrum ranging from 1500 to 1600 nm at room temperature. The light emission enhancement is due to Purcell effect and high collection efficiency of the PCRR verified by calculated far-field patterns. The Purcell factor of the PCRR is estimated from enhancement factor and increased collection efficiency. The linewidth of the emission of a single Ge quantum dot is estimated from the Purcell factor.

Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Direct investigation and accurate control of phase profile in liquid-crystal optical-phased array for beam steering.

An experimental setup and simple method were proposed to investigate and control the actual phase profile in a high-spatial-resolution liquid-crystal optical-phased array (LCOPA). A crossed polarizer and high-resolution microscope objective were employed to transform the light distribution out of the liquid-crystal layer into a polarization-interference pattern in which the phase-profile information was wrapped. The polarization-interference pattern was then directly translated into the actual phase profile. Based on this setup, a method was developed to accurately control the actual phase profile, and the steering efficiency at the steering angle of 16 mrad was increased from 80% to 90%. The proposed method also helps in increasing the steering efficiency when disclination lines appear.

Diaqua-bis-(1H-imidazole-4-carboxyl-ato-κ(2) N (3),O (4))manganese(II).

In the title compound, [Mn(C4H3N2O2)2(H2O)2], the Mn(II) ion is located on a twofold rotation axis and displays a distorted octa-hedral coordination environment, defined by two N,O-bidentate 1H-imidazole-4-carboxyl-ate ligands in the equatorial plane and two water mol-ecules in axial positions. In the crystal, O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular network. π-π stacking inter-actions between the imidazole rings [centroid-centroid distances = 3.5188 (15) and 3.6687 (15) Å] further stabilize the structure.

Fluorescent double network ionogels with fast self-healability and high resilience for reliable human motion detection.

Fascinating properties are displayed by high-performance ionogel-based flexible strain sensors, thereby gaining increasing attention in various applications ranging from human motion monitoring to soft robotics. However, the integration of excellent properties such as optical and mechanical properties and satisfactory sensing performance for one ionogel sensor is still a challenge. In particular, fatigue-resistant and self-healing properties are essential to continuous sensing. Herein, we design a flexible ion-conductive sensor based on a multifunctional ionogel with a double network using polyacrylamide, amino-modified agarose, 1,3,5-benzenetricarboxaldehyde and 1-ethyl-3-methylimidazolium chloride. The ionogel exhibits comprehensive properties including high transparency (>95%), nonflammability, strong adhesion and good temperature tolerance (about -96 to 260 °C), especially adaptive for extreme conditions. The dynamic imine bonds and abundant hydrogen bonds endow the ionogel with excellent self-healing capability, to realize rapid self-repair within minutes, as well as good mechanical properties and ductility to dissipate input energy and realize high resilience. Notably, unexpected fluorescence has been observed for the ionogel because of the gelation-induced emission phenomenon. Flexible strain sensors prepared directly from ionogels can sensitively monitor and differentiate various human motions, exhibiting a fast response time (38 ms), high sensitivity (gauge factor = 3.13 at 800% strain), good durability (>1000 cycles) and excellent stability over a wide temperature range (-30 to 80 °C). Therefore, the prepared ionogel as a high-performance flexible strain sensor in this study shows tremendous potential in wearable devices and soft ionotronics.

PRDM16 deficiency in vascular smooth muscle cells aggravates abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain-containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell-specific (VSMC-specific) Prdm16-knockout (Prdm16SMKO) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in Prdm16SMKO mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling. Prdm16 deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC apoptosis induced by Prdm16 deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.

Tunable liquid crystal microlens array using hole patterned electrode structure with ultrathin glass slab.

A configuration of hole patterned electrode liquid crystal microlens array with an ultrathin glass slab was fabricated. To reduce the fringing electric field effect and avoid the occurrence of disclination lines, an ultrathin glass slab was introduced between the patterned electrode and liquid crystal layer. The glass slab thickness played an important role in effecting the optical performance of the liquid crystal microlens array. An optimum thickness of 30 µm was selected employing numerical simulation method. Using this method, we demonstrated a microlens array that greatly improved the phase profile and focus power. The dynamic focal range of the liquid crystal microlens array may extend from <1.2 mm to >8 mm and the minimum diameter of the focus spot could be as small as 15 µm.

A facile and efficient synthesis approach of salidroside esters by whole-cell biocatalysts in organic solvents.

Salidroside, the main bioactive compound isolated from the plant source of Rhodiola rosea L, possesses broad-spectrum pharmacological activities, but suffers from the low cell membranes permeability and alimentary absorption due to its high polarity. Therefore, a whole-cell catalytic strategy for the synthesis of salidroside esters was explored to improve its lipophilicity. The results showed that Aspergillus oryzae demonstrated the highest biocatalytic activity among the microbial strains tested. For the synthesis of salidroside caprylate, the optimum conditions of reaction medium, Aspergillus oryzae amount, molar ratio of vinyl caprylate to salidroside and reaction temperature were acetone, 30 mg/ml, 10°C and 40°C, respectively. Under these conditions, the initial reaction rate was 15.36 mM/h, and substrate conversion and regioselectivity all reached 99%. Moreover, the results indicated that although various 6'-monoesters derivatives of salidroside were exclusively obtained with excellent conversions (96%-99%), the reaction rate varied greatly with different chain-length acyl donors. This study details an efficient and cost-effective biocatalytic approach for the synthesis of salidroside esters by using Aspergillus oryzae as a catalyst for the first time. Considering the whole cell catalytic efficiency and operational stability, this strategy may provide a new opportunity to develop green industrial processes production for ester derivatives of salidroside and its analogues.