Broadband 2 × 2 multimode-interference coupler on the silicon-nitride platform.

In this paper, we present the design, optimization, and implementation of a sub-wavelength grating (SWG) multi-mode interference coupler (MMI) on the silicon nitride photonic integrated circuit (PIC) platform with a significantly enhanced bandwidth compared to the conventional MMI. We extend the SWG MMI theory, previously presented for the silicon-on-insulator platform, to the Si3N4/SiO2 platform. Our approach involves an initial parameter optimization for a non-paired design, followed by a shift to a paired design that offers a smaller footprint and a broader bandwidth. The optimized SWG MMI exhibits a 1 dB bandwidth of 300 nm for both the insertion loss and power imbalance, making it a significant addition to silicon nitride photonics.

Nonlocal metasurface for dark-field edge emission.

Nonlocal effects originating from interactions between neighboring meta-atoms introduce additional degrees of freedom for peculiar characteristics of metadevices, such as enhancement, selectivity, and spatial modulation. However, they are generally difficult to manipulate because of the collective responses of multiple meta-atoms. Here, we experimentally demonstrate the nonlocal metasurface to realize the spatial modulation of dark-field emission. Plasmonic asymmetric split rings (ASRs) are designed to simultaneously excite local dipole resonance and nonlocal quasi-bound states in the continuum and spatially extended modes. With one type of unit, nonlocal effects are tailored by varying array periods. ASRs at the metasurface's edge lack sufficient interactions, resulting in stronger dark-field scattering and thus edge emission properties of the metasurface. Pixel-level spatial control is demonstrated by simply erasing some units, providing more flexibility than conventional local metasurfaces. This work paves the way for manipulating nonlocal effects and facilitates applications in optical trapping and sorting at the nanoscale.

Impact of Antenatal SARS-CoV-2 Exposure on SARS-CoV-2 Neutralization Potency.

A pregnancy booster dose significantly reduces the risk and severity of COVID-19, and it is widely recommended. A prospective cohort study was conducted to compare the transplacental passage of maternal antibodies from vaccination or infection during three trimesters against both the vaccine-targeted Wuhan strain and the Omicron strain of SARS-CoV-2. Maternal-infant dyads from vaccinated mothers were collected between 6 June 2022 and 20 September 2022. We analyzed 38 maternal-infant dyads from mothers who had been infected with COVID-19 and 37 from mothers without any previous infection. Pregnant women who received their last COVID-19 vaccine dose in the third trimester exhibited the highest anti-spike protein antibody levels and neutralizing potency against both the Wuhan strain and Omicron BA.2 variant in their maternal and cord plasma. Both second- and third-trimester vaccination could lead to a higher level of neutralization against the Wuhan and Omicron strains. COVID-19 infection had a negative effect on the transplacental transfer ratio of SARS-CoV-2 antibodies. A booster dose during the second or third trimester is encouraged for the maximum transplacental transfer of humoral protection against COVID-19 for infants.

High-fat diet induces C-reactive protein secretion, promoting lung adenocarcinoma via immune microenvironment modulation.

To understand the effects of a high-fat diet (HFD) on lung cancer progression and biomarkers, we here used an inducible mutant epidermal growth factor receptor (EGFR)-driven lung cancer transgenic mouse model fed a regular diet (RD) or HFD. The HFD lung cancer (LC-HFD) group exhibited significant tumor formation and deterioration, such as higher EGFR activity and proliferation marker expression, compared with the RD lung cancer (LC-RD) group. Transcriptomic analysis of the lung tissues revealed that the significantly changed genes in the LC-HFD group were highly enriched in immune-related signaling pathways, suggesting that an HFD alters the immune microenvironment to promote tumor growth. Cytokine and adipokine arrays combined with a comprehensive analysis using meta-database software indicated upregulation of C-reactive protein (CRP) in the LC-HFD group, which presented with increased lung cancer proliferation and metastasis; this was confirmed experimentally. Our results imply that an HFD can turn the tumor growth environment into an immune-related pro-tumorigenic microenvironment and demonstrate that CRP has a role in promoting lung cancer development in this microenvironment.

High-Resolution Metalens Imaging with Sequential Artificial Intelligence Models.

An analysis of the optical response of a GaN-based metalens was conducted alongside the utilization of two sequential artificial intelligence (AI) models in addressing the occasional issues of blurriness and color cast in captured images. The optical loss of the metalens in the blue spectral range was found to have resulted in the color cast of images. Autoencoder and CodeFormer sequential models were employed in order to correct the color cast and reconstruct image details, respectively. Said sequential models successfully addressed the color cast and reconstructed details for all of the allocated face image categories. Subsequently, the CIE 1931 chromaticity diagrams and peak signal-to-noise ratio analysis provided numerical evidence of the AI models' effectiveness in image reconstruction. Furthermore, the AI models can still repair the image without blue information. Overall, the integration of metalens and artificial intelligence models marks a breakthrough in enhancing the performance of full-color metalens-based imaging systems.

Rail Corrugation Index Development by Sound-Field Excitation on the Carriage Floor of In-Service Train.

The steel rail and wheel in the railway system offer a high precision and smooth-running surface. Nevertheless, the point of contact between the rail and wheel presents a critical area that can give rise to rail corrugation. This phenomenon can potentially elevate sound and vibration levels in the vicinity considerably, necessitating advanced monitoring and assessment measures. Recently, many efforts have been directed towards utilizing in-service trains for evaluating rail corrugation, and the evaluation has primarily relied on axle-box acceleration (ABA). However, the ABA measurements require a higher threshold for vibration detection. This study introduces a novel approach to rail corrugation detection by carriage floor acceleration (CFA), aimed at lowering the detection threshold. The method capitalizes on the acceleration data sensed on the carriage floor, which is induced by the sound pressure (e.g., sound-field excitation) generated at the wheel-rail contact point. An exploration of the correlation between these datasets is undertaken by simultaneously measuring both ABA and CFA. Moreover, a pivotal aspect of this research is the development of the eigenfrequency rail corrugation index (E-RCI), a mechanism that culminates energy around specific eigenfrequencies by CFA. Through this index, a focused analysis of rail corrugation patterns is facilitated. The study further delves into the stability, repeatability, and sensitivity of the E-RCI via varied measurement scenarios. Ultimately, the CFA-based rail corrugation identification is verified, establishing its practical applicability and offering a distinct approach to detecting and characterizing rail corrugation phenomena. This study has introduced an innovative methodology for rail corrugation detection using CFA, with the principal objective of lowering the detection threshold. This approach offers an efficient measurement technique for identifying rail corrugation areas, thereby potentially reducing maintenance costs and enhancing efficiency within the railway industry.

LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway.

Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize its physiological function, we generate LCRMP-1-deficient mice (Lcrmp-1-/-). These mice exhibit aberrant spermiation with apoptotic spermatids, oligospermia, and accumulation of immature testicular cells, contributing to reduced fertility. In the seminiferous epithelial cycle, LCRMP-1 expression pattern varies in a stage-dependent manner. LCRMP-1 is highly expressed in spermatids during spermatogenesis and especially localized to the spermiation machinery during spermiation. Mechanistically, LCRMP-1 deficiency causes disorganized F-actin due to unbalanced signaling of F-actin dynamics through upregulated PI3K-Akt-mTOR signaling. In conclusion, LCRMP-1 maintains spermatogenesis homeostasis by modulating cytoskeleton remodeling for spermatozoa release.

Identification of Ndfip1 as a novel negative regulator for spatial memory formation associated with increased ubiquitination of Beclin 1 and PTEN.

Long-term memory formation requires de novo RNA and protein synthesis. By using the differential display-polymerase chain reaction strategy, we have presently identified the Nedd4 family interacting protein 1 (Ndfip1) cDNA fragment that is differentially expressed between the slow learners and the fast learners from the water maze learning task in rats. Further, the fast learners show decreased Ndfip1 mRNA and protein expression levels than the slow learners. Spatial training similarly decreases the Ndfip1 mRNA and protein expression levels. Conversely, the Ndfip1 conditional heterozygous (cHet) mice show enhanced spatial memory performance compared to the Ndfip1flox/WT control mice. Result from co-immunoprecipitation experiment indicates that spatial training decreases the association between Ndfip1 and the E3 ubiquitin ligase Nedd4 (Nedd4-1), and we have shown that both Beclin 1 and PTEN are endogenous ubiquitination targets of Nedd4 in the hippocampus. Further, spatial training decreases endogenous Beclin 1 and PTEN ubiquitination, and increases Beclin 1 and PTEN expression in the hippocampus. On the other hand, the Becn1 conditional knockout (cKO) mice and the Pten cKO mice both show impaired spatial learning and memory performance. Moreover, the expression level of Beclin 1 and PTEN is higher in the Ndfip1 cHet mice compared with the Ndfip1flox/WT control mice. Here, we have identified Ndfip1 as a candidate novel negative regulation for spatial memory formation and this is associated with increased ubiquitination of Beclin 1 and PTEN in the hippocampus.

Suppression of wetting transition on evaporative fakir droplets by using slippery superhydrophobic surfaces with low depinning force.

This study experimentally investigated the evaporation and wetting transition behavior of fakir droplets on five different microstructured surfaces. Diamond-like carbon was introduced as the substrate, and the influence of varying the width, height, and pitch of the micropillars was assessed. The experimental results showed that the interfacial properties of the surfaces change the evaporation behavior and the starting point of the wetting transition. An important result of this study is the demonstration of a slippery superhydrophobic surface with low depinning force that suppresses the transition from the Cassie-Baxter state to the Wenzel state for microdroplets less than 0.37 mm in diameter, without employing large pillar height or multiscale roughness. By selecting an appropriate pillar pitch and employing tapered micropillars with small pillar widths, the solid-liquid contact at the three-phase contact line was reduced and low depinning forces were obtained. The underlying mechanism by which slippery superhydrophobic surfaces suppress wetting transitions is also discussed. The accuracy of the theoretical models for predicting the critical transition parameters was assessed, and a numerical model was developed in the surface evolver to compute the penetration of the droplet bottom meniscus within the micropillars.

Design and implementation of a Si3N4 three-stigmatic-point arrayed waveguide grating with a resolving power over 17,000.

To provide a solution to the issue of the non-flat focal surface in traditional Rowland AWGs, we have designed and implemented a Si3N4 three-stigmatic-point arrayed waveguide grating (TSP AWG) with three inputs, and a spectral resolving power over 17,000 has been achieved experimentally. The flat focal surface of this AWG can accommodate a butt-coupled detector array positioned at the output facet without any reduction of the resolving power of the edge channels. Therefore, it is particularly advantageous to some astronomical applications which require an AWG as a light-dispersing component to obtain a complete 2D spectrum. As a proof-of-concept for next generation devices, the multi-input aspect of the design accommodates multiple single-mode fibers coming into the AWG. In addition, because the device is implemented on a high-index-contrast platform (Si3N4/SiO2), a compact size of ∼9.3 × 9.3 mm2 is achieved.

Antireflection of optical anisotropic dielectric metasurfaces.

We propose a hetero-nano-fin structure to further improve the efficiency of Pancharatnam-Berry phase metasurfaces. Two hetero-nano-fin types, MgF2/GaN and MgF2/Nb2O5, were investigated. The overall polarization conversion efficiency (PCE) improved from 52.7 to 54% for the MgF2/GaN nano-fin compared with the bare GaN nano-fin. The overall PCE of the Nb2O5 nano-fin was 1.7 times higher than that of the GaN nano-fin. The overall PCE improved from 92.4% up to 96% after the application of MgF2 antireflection. Moreover, the antireflection improves efficiency by an average of 4.3% in wavelengths from 450 to 700 nm. Although the increment of energy seems minimal, antireflection is crucial for a metasurface, not only enhancing efficiency but also reducing background signal of a meta-device.

Blockage of Nrf2 and autophagy by L-selenocystine induces selective death in Nrf2-addicted colorectal cancer cells through p62-Keap-1-Nrf2 axis.

Persistent Nrf2 activation is typically noted in many cancers, including colorectal cancer (CRC), aiding cancer cells in overcoming growth stress and promoting cancer progression. Sustained Nrf2 activation, which is beneficial for cancer cells, is called "Nrf2 addiction"; it is closely associated with malignancy and poor prognosis in patients with cancer. However, Nrf2 inhibitors may have adverse effects on normal cells. Here, we found that the selenocompound L-selenocystine (SeC) is selectively cytotoxic in the Nrf2-addicted CRC cell line WiDr cells, but not in non-Nrf2-addicted mesenchymal stem cells (MSCs) and normal human colon cells. Another CRC cell line, C2BBe1, which harbored lower levels of Nrf2 and its downstream proteins were less sensitive to SeC, compared with the WiDr cells. We further demonstrated that SeC inhibited Nrf2 and autophagy activation in the CRC cells. Antioxidant GSH pretreatment partially rescued the CRC cells from SeC-induced cytotoxicity and Nrf2 and autophagy pathway inhibition. By contrast, SeC activated Nrf2 and autophagy pathway in non-Nrf2-addicted MSCs. Transfecting WiDr cells with Nrf2-targeting siRNA decreased persistent Nrf2 activation and alleviated SeC cytotoxicity. In KEAP1-knockdown C2BBe1 cells, Nrf2 pathway activation increased SeC sensitivity and cytotoxicity. In conclusion, SeC selectively attacks cancer cells with constitutively activated Nrf2 by reducing Nrf2 and autophagy pathway protein expression through the P62-Nrf2-antioxidant response element axis and eventually trigger cell death.

Selenocystine induces oxidative-mediated DNA damage via impairing homologous recombination repair of DNA double-strand breaks in human hepatoma cells.

Selenocystine (SeC) has been identified as a novel compound with broad-spectrum anticancer activity. However, the effects of SeC on modifying DNA repair mechanism were less addressed. In this study, we demonstrated that SeC selectively induced cytotoxicity and genotoxicity against HepG2 hepatoma cell line. Comet assay revealed SeC-induced DNA damage in HepG2 cells, particularly in the form of DNA double strand breaks (DSBs), corroborated by the increase expression of the DSB marker, gamma-H2AX. We further demonstrated that SeC suppressed DNA homologous recombination repair, exacerbating DNA damage accumulation. Such effects on DNA damage and cell viability inhibition were alleviated by antioxidants, glutathione and Trolox, suggesting the involvement of reactive oxygen species (ROS). High levels of intracellular and mitochondrial ROS were detected in SeC-treated HepG2. In addition, SeC impaired the expression of antioxidant enzymes (superoxidase mutases and catalase), prompting the imbalance between antioxidant protection and excessive ROS formation and eliciting DSBs and cellular death. Decreased procaspase-3, 7, and 9 and Bcl-2 proteins and an increased Bax/Bcl-2 ratio, were observed after SeC treatment, but could be reversed by Torlox, confirming the action of SeC on ROS-induced apoptosis. In vivo, the xenograft tumor model of HepG2 cells validated the inhibition of SeC on tumor growth, and the induction of DSBs and apoptosis. In summary, SeC has the capability to induce ROS-dependent DNA damage and impeded DBS repair in HepG2 cells. Thus, SeC holds great promise as a therapeutic or adjuvant agent targeting DNA repair for cancer treatment.

Review of Metasurfaces and Metadevices: Advantages of Different Materials and Fabrications.

Flat optics, metasurfaces, metalenses, and related materials promise novel on-demand light modulation within ultrathin layers at wavelength scale, enabling a plethora of next-generation optical devices, also known as metadevices. Metadevices designed with different materials have been proposed and demonstrated for different applications, and the mass production of metadevices is necessary for metadevices to enter the consumer electronics market. However, metadevice manufacturing processes are mainly based on electron beam lithography, which exhibits low productivity and high costs for mass production. Therefore, processes compatible with standard complementary metal-oxide-semiconductor manufacturing techniques that feature high productivity, such as i-line stepper and nanoimprint lithography, have received considerable attention. This paper provides a review of current metasurfaces and metadevices with a focus on materials and manufacturing processes. We also provide an analysis of the relationship between the aspect ratio and efficiency of different materials.

Review of component designs for post-COVID-19 HVAC systems: possibilities and challenges.

The globally occurring recurrent waves of the COVID-19 pandemic, primarily caused by the transmission of aerosolized droplets from an infected person to a healthy person in the indoor environment, has led to the urgency of designing new modes of indoor ventilation. To prevent cross-contaminations due to airborne viruses, bacteria, and other pollutants in indoor environments, heating ventilation and air-conditioning (HVAC) systems need to be redesigned with anti-pandemic components. The three vital anti-pandemic components for the post-COVID-19 HVAC systems, as identified by the authors, are: a biological contaminant inactivation unit, a volatile organic compound decomposition unit, and an advanced air filtration unit. The purpose of the current article is to provide an overview of the latest research outcomes toward designing these anti-pandemic components and pointing out the future promises and challenges. In addition, the role of personalized ventilation in minimizing the risk of indoor cross-contamination by employing various air terminal devices is discussed. The authors believe that this article will encourage HVAC designers to develop effective anti-pandemic components to minimize the indoor airborne transmission.

Evaluation of gas permeability in porous separators for polymer electrolyte fuel cells: Computational fluid dynamics simulation based on micro-x-ray computed tomography images.

Pore structures and gas transport properties in porous separators for polymer electrolyte fuel cells are evaluated both experimentally and through simulations. In the experiments, the gas permeabilities of two porous samples, a conventional sample and one with low electrical resistivity, are measured by a capillary flow porometer, and the pore size distributions are evaluated with mercury porosimetry. Local pore structures are directly observed with micro-x-ray computed tomography (CT). In the simulations, the effective diffusion coefficients of oxygen and the air permeability in porous samples are calculated using random walk Monte Carlo simulations and computational fluid dynamics (CFD) simulations, respectively, based on the x-ray CT images. The calculated porosities and air permeabilities of the porous samples are in good agreement with the experimental values. The simulation results also show that the in-plane permeability is twice the through-plane permeability in the conventional sample, whereas it is slightly higher in the low-resistivity sample. The results of this study show that CFD simulation based on micro-x-ray CT images makes it possible to evaluate anisotropic gas permeabilities in anisotropic porous media.

Investigation of entrance effects on particle electrophoretic behavior near a nanopore for resistive pulse sensing.

Resistive pulse sensing using solid-state nanopores provides a unique platform for detecting the structure and concentration of molecules of different types of analytes in an electrolyte solution. The capture of an entity into a nanopore is subject not only to the electrostatic force but also the effect of electroosmotic flow originating from the charged nanopore surface. In this study, we theoretically analyze spherical particle electrophoretic behavior near the entrance of a charged nanopore. By investigating the effects of pore size, particle-pore distance, and salt concentration on particle velocity, we summarize dominant mechanisms governing particle behavior for a range of conditions. In the literature, the Helmholtz-Smoluchowski equation is often adopted to evaluate particle translocation by considering the zeta potential difference between the particle and nanopore surfaces. We point out that, due to the difference of the electric field inside and outside the nanopore and the influence from the existence of the particle itself, the zeta potential of the particle, however, needs to be at least 30% higher than that of the nanopore to allow the particle to enter into the nanopore when its velocity is close to zero. Accordingly, we summarize the effective salt concentrations that enable successful particle capture and detection for different pore sizes, offering direct guidance for nanopore applications.

Molecular dynamics study of water confined in MIL-101 metal-organic frameworks.

Molecular dynamics simulations of water adsorbed in Material Institute Lavoisier MIL-101(Cr) metal-organic frameworks are performed to analyze the kinetic properties of water molecules confined in the framework at 298.15 K and under different vapor pressures and clarify the water adsorption mechanism in MIL-101(Cr). The terahertz frequency-domain spectra (THz-FDS) of water are calculated by applying fast Fourier transform to the configurational data of water molecules. According to the characteristic frequencies in the THz-FDS, the dominant motions of water molecules in MIL-101(Cr) can be categorized into three types: (1) low-frequency translational motion (0-0.5 THz), (2) medium-frequency vibrational motion (2-2.5 THz), and (3) high-frequency vibrational motion (>6 THz). Each type of water motion is confirmed by visualizing the water configuration in MIL-101(Cr). The ratio of the number of water molecules with low-frequency translational motion to the total number of water molecules increases with the increase in vapor pressure. In contrast, that with medium-frequency vibrational motion is found to decrease with vapor pressure, exhibiting a pronounced decrease after water condensation has started in the cavities. That with the high-frequency vibrational motion is almost independent of the vapor pressure. The interactions between different types of water molecules affect the THz-FDS. Furthermore, the self-diffusion coefficient and the velocity auto-correlation function are calculated to clarify the adsorption state of the water confined in MIL-101(Cr). To confirm that the general trend of the THz-FDS does not depend on the water model, the simulations are performed using three water models, namely, rigid SPC/E, flexible SPC/E, and rigid TIP5PEw.

Melatonin Induction of APP Intracellular Domain 50 SUMOylation Alleviates AD through Enhanced Transcriptional Activation and Aß Degradation.

The amyloid precursor protein (APP) intracellular domain (AICD) is implicated in the pathogenesis of Alzheimer's disease (AD), but post-translational modification of AICD has rarely been studied and its role in AD is unknown. In this study, we examined the role and molecular mechanism of AICD SUMOylation in the pathogenesis of AD. We found that AICD is SUMO-modified by the SUMO E3 ligase protein inhibitor of activated STAT1 (PIAS1) in the hippocampus at Lys-43 predominantly, and that knockdown of PIAS1 decreases endogenous AICD SUMOylation. AICD SUMOylation increases AICD association with its binding protein Fe65 and increases AICD nuclear translocation. Furthermore, AICD SUMOylation increases AICD association with cyclic AMP-responsive element binding protein (CREB) and p65 and their DNA binding for transcriptional activation of neprilysin (NEP) and transthyretin (TTR), two major Aß-degrading enzymes, respectively. Consequently, AICD SUMOylation decreases the Aß level, Aß oligomerization, and amyloid plaque deposits. It also rescues spatial memory deficits in APP/PS1 mice. Conversely, blockade of AICD SUMOylation at Lys-43 produces the opposite effects. Melatonin is identified as an endogenous stimulus that induces AICD SUMOylation. It also decreases the Aß level and rescues reduction of PIAS1, NEP, and TTR expression in APP/PS1 mice. In this study, we demonstrate that AICD SUMOylation functions as a novel endogenous defense mechanism to combat AD.

Nanoconfined Electrochemical Sensing of Single Silver Nanoparticles with a Wireless Nanopore Electrode.

Single entity electrochemistry (SEE) has emerged as a promising method for precise measurement and fundamental understanding of the heterogeneity of single entities. Herein, we propose the dual responsive SEE sensing of the silver nanoparticles (AgNPs) collisions through a wireless nanopore electrode (WNE). Given the high temporal resolution and low background noise features, the Faradaic and capacitive currents provide the AgNPs' collision response. The electron transfer between the AgNPs and the electrode surface is identified under a bipolar electrochemical mechanism. Compared to the ultramicroelectrode, multistep oxidation of 30 nm AgNPs is observed due to the decreased interaction of the nanoparticles to the electrode. Moreover, the nanoconfinement of WNE plays a vital role in the repeated capturing of nanoparticles from the nontunneling region into the tunneling region until a complete oxidation. As a comparison, the collision of 5 nm AgNPs with higher interaction at the electrode surface shows great decrease in the multistep events. Thus, we propose a nanoconfined interaction based SEE method which could be used for simultaneously capturing the Faradaic and capacitive response. The nanoconfined interaction based SEE method holds great promise in the better understanding of heterogeneity of single particles.