Inhibiting α1-adrenergic receptor signaling pathway ameliorates AD-type pathologies and behavioral deficits in APPswe/PS1 mouse model.

The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (α1-ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH-SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1-ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aß species, compact and total Aß plaques, than control mice. α1-ARs inhibitor terazosin substantially reduced Aß deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3ß, thus reducing Aß production. This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Visible-light metalens far-field nanofocusing effects with active tuning of focus based on MIM subwavelength structures used in an integrated imaging array.

We propose a structure of a far-field nanofocusing metalens with focal shifting that is actively tuned at visible wavelengths. Surface plasmon polaritons (SPPs) can be excited by the metal-insulator-metal (MIM) subwavelength structure at visible wavelengths. The coherent interference of SPPs emitted by subwavelength nanostructures can form a nanoscale focus. When the SPPs are excited and pass through several concentric ring gratings with specific aspect ratios, the extraordinary optical transmission phenomenon occurs. Two metal concentric ring gratings achieve double diffraction, scattering light to the far field. An anisotropic or isotropic electrically adjustable refractive index material, such as liquid-crystal or optical phase change material, is filled in a dielectric layer between two metal layers, and the effective refractive index is modulated by electronically controlled active tuning. The focal shift is achieved by changing the effective refractive index of the intermediate dielectric. In addition, different incident wavelengths correspond to different effective refractive indices to achieve time-division-multiplexing multi-wavelength achromatic focusing. The finite-difference time-domain method was used to simulate the effect of substrate effective refractive index variation on achromatic superfocusing. The results show that the super-resolution focal spot (FWHM=0.158λ0) with long focal length (FL=5.177λ0) and large depth of field (DOF=3.412λ0) can be achieved by optimizing the design parameters. The visible plasma metalens has potential applications in high-density optical storage and optical microscopic imaging, especially in three-dimensional display for light field and integral imaging.

Motion parallax and lossless resolution autostereoscopic 3D display based on a binocular viewpoint tracking liquid crystal dynamic grating adaptive screen.

The autostereoscopic 3D display has two important indicators, both the number of viewpoints and display resolution. However, it's a challenge to improve both the viewpoint and the resolution. Here, we develop a fixed-position multiview and lossless resolution autostereoscopic 3D display system that includes the dynamic liquid crystal (LC) grating screen. This display system consists of an LC display panel and an LC grating screen. The synchronization of the frame switching of the LC display panel and the LC grating screen shutter enables the preserved resolution. The "eye space" design makes the viewpoint dense enough and determines the LC grating screen's parameters. We use binocular viewpoint tracking technology to realize the LC grating screen's adaptive control based on the above work. Different binocular views are rendered in real-time according to the different positions of a single pair of stereoscopic viewpoints in the eye space, making the motion parallax possible. We present the working principle and mathematical analysis. We implement a prototype for verifying the principle. According to the experiment results analysis, this prototype can achieve viewpoint tracking and motion parallax based on resolution lossless and viewpoint dense enough.

Structural design of cobalt phosphate on nickel foam for electrocatalytic oxygen evolution.

The elaborate design and synthesis of low-cost, efficient and stable electrocatalysts for the oxygen evolution reaction (OER), which may alleviate the current energy shortage and environment pollution, is still a great challenge. Herein, metal phosphonate precursors with controllable morphologies were synthesizedin situon the surface of nickel foam with different solvents, and could be easily converted into carbon- and nitrogen-doped cobalt phosphate through a calcination method. The OER catalytic performance of the final products was studied in detail. The results showed that the nanowire shaped samples of CoPiNF-800 synthesized with deionized water under hydrothermal conditions had the strongest electrochemical performance. They exhibited extraordinary catalytic activity with a very low overpotential of 222 mV at 100 mA cm-2, the smallest impedance and excellent electrochemical stability. These results not only demonstrate the possibility of preparing low-cost OER catalysts based on transition metal phosphate, but also aid our understanding of the controllable synthesis process of different morphologies.

Online Medical Record Nonuse Among Patients: Data Analysis Study of the 2019 Health Information National Trends Survey.

BACKGROUND: Online medical records are being used to organize processes in clinical and outpatient settings and to forge doctor-patient communication techniques that build mutual understanding and trust. OBJECTIVE: We aimed to understand the reasons why patients tend to avoid using online medical records and to compare the perceptions that patients have of online medical records based on demographics and cancer diagnosis. METHODS: We used data from the Health Information National Trends Survey Cycle 3, a nationally representative survey, and assessed outcomes using descriptive statistics and chi-square tests. The patients (N=4328) included in the analysis had experienced an outpatient visit within the previous 12 months and had answered the online behavior question regarding their use of online medical records. RESULTS: Patients who were nonusers of online medical records consisted of 58.36% of the sample (2526/4328). The highest nonuser rates were for patients who were Hispanic (460/683, 67.35%), patients who were non-Hispanic Black (434/653, 66.46%), and patients who were older than 65 years (968/1520, 63.6%). Patients older than 65 years were less likely to use online medical records (odds ratio [OR] 1.51, 95% CI 1.24-1.84, P<.001). Patients who were White were more likely to use online medical records than patients who were Black (OR 1.71, 95% CI 1.43-2.05, P<.001) or Hispanic (OR 1.65, 95% CI 1.37-1.98, P<.001). Patients who were diagnosed with cancer were more likely to use online medical records compared to patients with no cancer (OR 1.31, 95% CI 1.11-1.55, 95% CI 1.11-1.55, P=.001). Among nonusers, older patients (≥65 years old) preferred speaking directly to their health care providers (OR 1.76, 95% CI 1.35-2.31, P<.001), were more concerned about privacy issues caused by online medical records (OR 1.79, 95% CI 1.22-2.66, P<.001), and felt uncomfortable using the online medical record systems (OR 10.55, 95% CI 6.06-19.89, P<.001) compared to those aged 18-34 years. Patients who were Black or Hispanic were more concerned about privacy issues (OR 1.42, 1.09-1.84, P=.007). CONCLUSIONS: Studies should consider social factors such as gender, race/ethnicity, and age when monitoring trends in eHealth use to ensure that eHealth use does not induce greater health status and health care disparities between people with different backgrounds and demographic characteristics.

Ultra-broadband large-angle beam splitter based on a homogeneous metasurface at visible wavelengths.

Metasurface-based beam splitters with high efficiency, large split angle, wide bandwidth and easy fabrication are highly desirable and still in pursuit. In this paper, we propose a heuristic scheme for designing an ultra-broadband high-efficiency power beam splitter based on a homogeneous metasurface. The conversion efficiency and total transmission intensity of the power splitter stays higher than 95% and 0.66 within the wavelength region from 604 nm to 738 nm, respectively. Particularly, the conversion efficiency can maintain greater than 99% in 58 nm bandwidth. The angle between two split beams can reach a maximum of 157.82° at the wavelength of 738 nm. In addition to simplified design and easy fabrication, the proposed power beam splitter possesses high robustness as well. We expect that our design can pave a new way for realizing high-performance metasurface-based beam splitters.

Beyond dipole excitation: the performance of quadrupole-based Huygens' metasurface.

Due to the utilization of overlapped dipole resonances, traditional Huygens' metasurfaces suffer from dipole interactions. In this Letter, we propose a design of phase-gradient Huygens' metasurface based on the quadrupole resonances excited in the cross-shaped structures. The quadrupole resonances are theoretically shown insensitive to the quadrupole interactions. Benefiting from this intrinsic property, the proposed metasurface can well suppress element interaction influence and exhibits some impressive properties, including the ability to suppress high diffraction orders, tunable anomalous refractive angles, and high transmission efficiency. The numerical results show promising potential for quadrupole resonances to be applied in advanced Huygens' metasurface designs.

Realization of perfect selective absorber based on multipole modes in all-dielectric moth-eye structure.

Perfect absorbers play crucial roles in optical functional devices. Among various types of absorbers, moth-eye structures are known for their excellent absorbing efficiency. In this paper, we apply an electromagnetic multipole expansion method to treat an isolated all-dielectric moth-eye structure as a large particle and calculate various electric and magnetic multipole modes within the moth-eye structure. In periodical array, the multipole modes within each particle interact with each other. These constructive or destructive interactions cause shifts in the multipole resonant peaks. The multipole modes inside the particle array introduce reflecting peaks for loss-less materials. The absorption enhancement inside moth-eye structures can be attributed to the electric field enhancement resulting from these electric and magnetic multipole modes. Based on our theoretical study, we propose a near-ideal selective absorber based on moth-eye array, which achieves near 100% absorption within wavelength range from 400 nm to 1500 nm while achieving near 0% absorption over about 1700 nm.

Design of spontaneous parametric down-conversion in integrated hybrid SixNy-PPLN waveguides.

High-efficient and high-purity photon sources are highly desired for quantum information processing. We report the design of a chip-scale hybrid SixNy and thin film periodically-poled lithium niobate waveguide for generating high-purity type-II spontaneous parametric down-conversion (SPDC) photons in the telecommunication band. The modeled second harmonic generation efficiency of 225% W-1 • cm-2 is obtained at 1560nm. Joint spectral analysis is performed to estimate the frequency correlation of SPDC photons, yielding intrinsic purity with up to 95.17%. The generation rate of these high-purity photon pairs is estimated to be 2.87 × 107 pairs/s/mW within the bandwidth of SPDC. Our chip-scale hybrid waveguide design has the potential for large-scale on-chip quantum information processing and integrated photon-efficient quantum key distribution through high-dimensional time-energy encoding.

Mechanisms of 2π phase control in dielectric metasurface and transmission enhancement effect.

Metasurfaces, two-dimensional structures composed of nanoantennas in an array configuration, can be used to fully control electromagnetic waves, which requires a 2π phase shift. Herein, we apply the silicon metasurface as an example to interpret the mechanisms of full 2π phase coverage. It is found that the mechanism varies from Fabry-Pérot resonance to Mie resonance as the period increases for a metasurface with certain height. Particularly, there is a transition region between these two types of resonance. We present the corresponding periods and wavelength regions of the different mechanisms when considering the phase-gradient metasurface with at most three diffraction orders. Moreover, the transmission enhancement of metasurface is investigated. The transmission efficiency can be effectively improved when the nanoantenna is changed from a uniform structure to a gradient-index one. We expect that the results can simplify the design process and provide a reference for the future design of all-dielectric metasurface with 2π phase control.

Gate-tunable optical filter based on conducting oxide metasurface heterostructure.

A gate-tunable plasmonic optical filter incorporating a subwavelength patterned metal-insulator-metal metasurface heterostructure is proposed. An additional thin transparent conducting oxide (TCO) layer is embedded in the insulator layer to form a double metal-oxide-semiconductor configuration. Heavily n-doped indium tin oxide (ITO) is employed as the TCO material, whose optical property can be electrically tuned by the formation of a thin active epsilon-near-zero layer at the ITO-oxide interfaces. Full-wave electromagnetic simulations show that amplitude modulation and shift of transmission peak are achievable with 3-5 V applied bias, depending on the application. Moreover, the modulation strength and transmission peak shift increase with a thinner ITO layer. This work is an essential step toward a realization of next-generation compact photonic/plasmonic integrated devices.

Numerical simulation and experimental verification of a dense multi-view full-resolution autostereoscopic 3D-display-based dynamic shutter parallax barrier.

We came up with a practical setup and simulation for building a glassless autostereoscopic 3D display system based on the concept of "eye space" with a dynamic shutter parallax barrier. "Eye space" is designed based on geometrical optics to get a multi-view as much as possible by adjusting the width of the slit and parallax barrier dynamically. The dynamic parallax barrier is placed in front of the display screen to form the shutter screen. The addressable drive circuit controls the switches of the pupil windows on the shutter screen. The two signals are synchronous with the drive circuit and the frame frequency scanning of the display screen. The shutter parallax barrier makes it possible that all right and left eyes in the "eye space" see their own views simultaneously. The numerical simulation and experimental verification with simplified 1D pupil windows and a field-programmable-gate-array-based driving circuit unit, which have good practical value, are described in this paper.

All-dielectric colored truncated cone metasurfaces with silicon Mie magnetic resonators.

We propose high-index truncated cone silicon metasurfaces based mainly on magnetic Mie resonances. From numerical simulation, the intensity of the reflection peak reaches almost 90%, and the full width at half-maximum (FWHM) of the reflectance spectrum is 43 nm. Specific colors covering the entire visible spectrum with saturation close to 1 are available by selecting appropriate geometric dimensions and period of the structure. In summary, the structural colors achieved by the proposed metasurfaces are superior to previous research in comprehensive aspects of reflection peak, the FWHM of the reflectance spectrum, and the saturation of the color. Furthermore, the proposed structure works with a low aspect ratio of 0.46, which largely relieves the difficulty of process manufacturing.

Policy Flight Simulators: Accelerating Decisions to Adopt Evidence-Based Health Interventions.

EXECUTIVE SUMMARY: In this study, the authors used simulation to explore factors that might influence hospitals' decisions to adopt evidence-based interventions. Specifically, they developed a simulation model to examine the extent to which hospitals would benefit economically from the transitional care model (TCM). The TCM is designed to transition high-risk older adults from hospitals back to communities using interventions focused on preventing readmissions.The authors used qualitative methods to identify and validate simulation facets. Four simulation experiments explored the economic impact of the TCM on more than 3,000 U.S. hospitals: (1) magnitude of readmission penalty, (2) application to specific diagnosis-related groups, (3) level of cost sharing between payer and provider, and (4) capitated versus fee-for-service payments. The simulator projected hospital-specific economic effects. The authors used Monte Carlo methods for the simulations, which were parameterized with public data sets from the Centers for Medicare & Medicaid Services (CMS) and TCM data from randomized controlled trials and comparative effectiveness studies.Under current conditions, the simulation indicated that only 10 of more than 3,000 Medicare-certified hospitals would benefit financially from the TCM. If current readmission penalties were doubled, the number of hospitals projected to benefit would increase to 300. Targeting selected diagnosis cohorts would also increase the number of hospitals to 300. If payers reimbursed providers for 100% of the TCM costs, 2,000 hospitals would benefit financially. Under a capitated payment model, 1,500 hospitals would benefit from the TCM.Current CMS penalties-or reasonable increases-have little economic effect on the TCM. In the current environment, two strategies are likely to facilitate adoption: (1) persuading payers to reimburse TCM costs and (2) focusing on hospitals with higher bed occupancies and higher revenue patients.

Underdetermined Wideband DOA Estimation for Off-Grid Sources with Coprime Array Using Sparse Bayesian Learning.

Sparse Bayesian learning (SBL) is applied to the coprime array for underdetermined wideband direction of arrival (DOA) estimation. Using the augmented covariance matrix, the coprime array can achieve a higher number of degrees of freedom (DOFs) to resolve more sources than the number of physical sensors. The sparse-based DOA estimation can deteriorate the detection and estimation performance because the sources may be off the search grid no matter how fine the grid is. This dictionary mismatch problem can be well resolved by the SBL using fixed point updates. The SBL can automatically choose sparsity and approximately resolve the non-convex optimizaton problem. Numerical simulations are conducted to validate the effectiveness of the underdetermined wideband DOA estimation via SBL based on coprime array. It is clear that SBL can obtain good performance in detection and estimation compared to least absolute shrinkage and selection operator (LASSO), simultaneous orthogonal matching pursuit least squares (SOMP-LS) , simultaneous orthogonal matching pursuit total least squares (SOMP-TLS) and off-grid sparse Bayesian inference (OGSBI).

Design of a broadband reciprocal optical diode in a silicon waveguide assisted by silver surface plasmonic splitter.

In this paper, we propose a new scheme for a reciprocal optical diode integrated in a multimode silicon waveguide. The compact 4µm long functional region consists of a tapered coupler, a narrow single-mode waveguide, and a half-elliptical silver surface plasmonic splitter with refractive index modification of silicon. This spatial asymmetric design achieves even-to-odd mode conversion in the forward direction and blocks propagation of the even mode in the backward direction. The maximum contrast ratio and forward transmission efficiency reach approximately 0.99 and 87% while the values respectively keep higher than 0.96 and 80% within a 100nm operational bandwidth in a two-dimensional design. Both freestanding and SOI-based three-dimensional devices are simulated and at least a 0.94 contrast ratio is observed. Moreover, the robustness is demonstrated by introducing deviations to the surface plasmonic splitter. The proposed scheme brings together advantages including a high contrast ratio (>0.94), a large operational bandwidth (100nm) and a small footprint (4µm long).

Chip-scale nanophotonic switch based on a waveguide-metamaterial coupling mechanism.

We demonstrate a simple and effective waveguide-metamaterial coupling mechanism to achieve switching control of the fundamental TE mode propagation in a silicon photonic stripe waveguide. The metamaterial is made of vertically stacked alternating ITO/Si layers and, theoretically, can be switched between transparent and absorptive regimes via modifying the carrier concentration of the ITO layers. In addition to its small footprint and CMOS-compatible fabrication, simulation results indicate that the optical switch features a high modulation depth (MD) of 27.8 dB, low insertion losses of 0.004 dB, and a wide operating bandwidth of 300 nm where the MD is >24.6 dB. We expect that this mechanism is a good candidate for designing high-performance and ultra-compact photonic devices in densely integrated nanophotonic circuits and computation systems.

Numerical study of an ultra-broadband near-perfect solar absorber in the visible and near-infrared region.

We propose and numerically investigate a novel ultra-broadband solar absorber by applying iron in a 2D simple metamaterial structure. The proposed structure can achieve the perfect absorption above 95% covering the wavelength range from 400 to 1500 nm. The average absorption reaches 97.8% over this wavelength range. The broadband perfect absorption is caused by the excitation of localized surface plasmon resonance and propagating surface plasmon resonance. We first propose and demonstrate that the iron is obviously beneficial to achieve impedance matching between the metamaterial structure and the free space over an ultra-broad frequency band in the visible and near-infrared region, which play an extremely important role to generate an ultra-broadband perfect absorption. In order to further broaden the absorption band, we also demonstrate the perfect absorption exceeding 92% for the 400-2000 nm range by adding the number of metal-dielectric pairs and using both gold and iron simultaneously in the proposed structure. The average absorption of the improved absorber reaches 96.4% over the range of 400-2000 nm. The metamaterial absorbers using iron are very promising for many applications, which can greatly broaden the perfect absorption band in the solar spectrum and, meanwhile, can enormously reduce the cost in the actual production.