Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and noradrenaline.The neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal system.Cholecystokinin(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target regions.For instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation.Conversely,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

Influence of substrate effect on near-field radiative modulator based on biaxial hyperbolic materials

Relative rotation between the emitter and receiver could effectively modulate the near-field radiative heat transfer(NFRHT)in anisotropic media.Due to the strong in-plane anisotropy,natural hyperbolic materials can be used to construct near-field radiative modulators with excellent modulation effects.However,in practical applications,natural hyperbolic materials need to be deposited on the substrate,and the influence of substrate on modulation effect has not been studied yet.In this work,we investigate the influence of substrate effect on near-field radiative modulator based onα-MoO_(3).The results show that compared to the situation without a substrate,the presence of both lossless and lossy substrate will reduce the modulation contrast(MC)for different film thicknesses.When the real or imaginary component of the substrate permittivity increases,the mismatch of hyperbolic phonon polaritons(HPPs)weakens,resulting in a reduction in MC.By reducing the real and imaginary components of substrate permittivity,the MC can be significantly improved,reaching 4.64 forε_(s)=3 at t=10 nm.This work indicates that choosing a substrate with a smaller permittivity helps to achieve a better modulation effect,and provides guidance for the application of natural hyperbolic materials in the near-field radiative modulator.

Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing E.coli challenged weaned piglets

Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

Light-field modulation and optimization near metal nanostructures utilizing spatial light modulators

Plasmonic modes within metal nanostructures play a pivotal role in various nanophotonic applications.However,a significant challenge arises from the fixed shapes of nanostructures post-fabrication,resulting in limited modes under ordinary illumination.A promising solution lies in far-field control facilitated by spatial light modulators(SLMs),which enable on-site,real-time,and non-destructive manipulation of plasmon excitation.Through the robust modulation of the incident light using SLMs,this approach enables the generation,optimization,and dynamic control of surface plasmon polariton(SPP)and localized surface plasmon(LSP)modes.The versatility of this technique introduces a rich array of tunable degrees of freedom to plasmon-enhanced spectroscopy,offering novel approaches for signal optimization and functional expansion in this field.This paper provides a comprehensive review of the generation and modulation of SPP and LSP modes through far-field control with SLMs and highlights the diverse applications of this optical technology in plasmon-enhanced spectroscopy.

Identification of FDA-Approved Drugs as Modulators of Multidrug Resistance Protein 2 (MRP2/ABCC2) Expression Levels in MRP2-Overexpressing Cells: Preliminary Data

Multidrug Resistance Protein 2 (MRP2) is an ATP-dependent transmembrane protein that plays a pivotal role in the efflux of a wide variety of physiological substrates across the plasma membrane. Several studies have shown that MRP2 can significantly affect the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of many therapeutic drugs and chemicals found in the environment and diet. This transporter can also efflux newly developed anticancer agents that target specific signaling pathways and are major clinical markers associated with multidrug resistance (MDR) of several types of cancers. MDR remains a major limitation to the advancement of the combinatorial chemotherapy regimen in cancer treatment. In addition to anticancer agents, MRP2 reduces the efficacy of various drug classes such as antivirals, antimalarials, and antibiotics. The unique role of MRP2 and its contribution to MDR makes it essential to profile drug-transporter interactions for all new and promising drugs. Thus, this current research seeks to identify modulators of MRP2 protein expression levels using cell-based assays. A unique recently approved FDA library (372 drugs) was screened using a high-throughput In-Cell ELISA assay to determine the effect of these therapeutic agents on protein expression levels of MRP2. A total of 49 FDA drugs altered MRP2 protein expression levels by more than 50% representing 13.17% of the compounds screened. Among the identified hits, thirty-nine (39) drugs increased protein expression levels whereas 10 drugs lowered protein expression levels of MRP2 after drug treatment. Our findings from this initial drug screening showed that modulators of MRP2 peregrinate multiple drug families and signify the importance of profiling drug interactions with this transporter. Data from this study provides essential information to improve combinatorial drug therapy and precision medicine as well as reduce the drug toxicity of various cancer chemotherapies.

A high-contrast imaging coronagraph for segmented-mirror large aperture telescopes using a spatial light modulator

The primary mirrors of current and future large telescopes always employ a segmented mirror configuration.The small but non-negligible gaps between neighboring segments cause additional diffraction,which restricts the performance of high-contrast coronagraph.To solve this problem,we propose a coronagraph system based on a single liquid crystal spatial light modulator(SLM).This spatial light modulator is used for amplitude apodization,and its feasibility and potential performance are demonstrated using a laboratory setup using the stochastic parallel gradient descent(SPGD)algorithm to control the spatial light modulator,which is based on point spread function(PSF)sensing and evaluation and optimized for maximum contrast in the discovery working area as a merit function.The system delivers a contrast in the order of 10−6,and shows excellent potential to be used in current and future large aperture telescopes,both on the ground and in space.

Harnessing immunity:Immunomodulatory therapies in COVID-19

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.

Crystallization Modulation and Holistic Passivation Enables Efficient Two‑Terminal Perovskite/CuIn(Ga)Se_(2)Tandem Solar Cells

Two-terminal(2-T)perovskite(PVK)/CuIn(Ga)Se_(2)(CIGS)tandem solar cells(TSCs)have been considered as an ideal tandem cell because of their best bandgap matching regarding to Shockley–Queisser(S–Q)limits.However,the nature of the irregular rough morphology of commercial CIGS prevents people from improving tandem device performances.In this paper,D-homoserine lactone hydrochloride is proven to improve coverage of PVK materials on irregular rough CIGS surfaces and also passivate bulk defects by modulating the growth of PVK crystals.In addition,the minority carriers near the PVK/C60 interface and the incompletely passivated trap states caused interface recombination.A surface reconstruction with 2-thiopheneethylammonium iodide and N,N-dimethylformamide assisted passivates the defect sites located at the surface and grain boundaries.Meanwhile,LiF is used to create this field effect,repelling hole carriers away from the PVK and C60 interface and thus reducing recombination.As a result,a 2-T PVK/CIGS tandem yielded a power conversion efficiency of 24.6%(0.16 cm^(2)),one of the highest results for 2-T PVK/CIGS TSCs to our knowledge.This validation underscores the potential of our methodology in achieving superior performance in PVK/CIGS tandem solar cells.

Ridge Waveguide Electro-Optic Polymer Modulator with a New Kind of Corona Poled Crosslinkable Polyurethane

A polymer electro optic modulator has been fabricated with the functional layer acting as a kind of corona poled crosslinkable polyurethane. The three optical layers, namely waveguide, photolithography and oxygen are fabricated by spin coating. With the Reactive Ion Etching method, the ridge of the waveguide is constructed. With light at 1 31μm being fiber coupled to waveguide, the mode and the modulation properties of these devices are demonstrated in a micron control system.

A 5mW 1.8V Low Over-Sampling Ratio ΣΔ Modulator with 81dB Dynamic Range

This work demonstrates that the ΣΔ modulator with a low oversampling ratio is a viable option for the high-resolution digitization in a low-voltage environment.Low power dissipation is achieved by designing a low-OSR modulator based on differential cascade architecture,while large signal swing maintained to achieve a high dynamic range in the low-voltage environment.Operating from a voltage supply of 1.8V,the sixth-order cascade modulator at a sampling frequency of 4-MHz with an OSR of 24 achieves a dynamic range of 81dB for a 80-kHz test signal,while dissipating only 5mW.

A High-Performance Silicon Electro-Optic Phase Modulator with a Triple MOS Capacitor

We propose and analyze a novel Si-based electro-optic modulator with an improved metal-oxide-semiconductor （MOS） capacitor configuration integrated into silicon-on-insulator （SOl）. Three gate-oxide layers embedded in the silicon waveguide constitute a triple MOS capacitor structure, which boosts the modulation efficiency compared with a single MOS capacitor. The simulation results demonstrate that the Vπ Lπ product is 2. 4V · cm. The rise time and fall time of the proposed device are calculated to be 80 and 40ps from the transient response curve, respectively,indicating a bandwidth of 8GHz. The phase shift efficiency and bandwidth can be enhanced by rib width scaling.

Monolithically Integrated Laser Diode and Electroabsorption Modulator with Dual-Waveguide Spot-Size Converter Output

A 1.60μm laser diode and electroabsorption modulator monolithically integrated with a novel dual-waveguide spot-size converter output for low-loss coupling to a cleaved single-mode optical fiber are demonstrated.The devices emit in a single transverse and quasi single longitudinal mode with an SMSR of 25.6dB.These devices exhibit a 3dB modulation bandwidth of 15.0GHz,and modulator DC extinction ratios of 16.2dB.The output beam divergence angles of the spot-size converter in the horizontal and vertical directions are as small as 7.3°×18.0°,respectively,resulting in a 3.0dB coupling loss with a cleaved single-mode optical fiber.

CMOS Quadrature Modulator and Up-Conversion Mixer for 802.11a Wireless LAN Systems

A quadrature modulator and an up-conversion mixer for an 802. lla wireless LAN system are designed and fabricated in 0.18μm gate length standard CMOS technology. A current feedback loop with a transconductor is used to improve the linearity of the quadrature modulator;An LC resonant tank is used as the load of the upconversion mixer to improve its gain and increase the voltage swing. The measurement results show that the input P1dB achieves -3.6dBm, the transducer power gain of the circuit is -3.6dB,and the current consumes about 45.8mA with a 1.8V power supply.

A Wavelength Tunable DBR Laser Integrated with an Electro-Absorption Modulator by a Combined Method of SAG and QWI

We report a wavelength tunable electro-absorption modulated DBR laser based on a combined method of SAG and QWI. The threshold current is 37mA and the output power at 100mA gain current is 3.5mW. When coupled to a single-mode fiber with a coupling efficiency of 15% ,more than a 20dB extinction ratio is observed over the change of EAM bias from 0 to -2V. The 4.4nm continuous wavelength tuning range covers 6 channels on a 100GHz grid for WDM telecommunications.

An Electroabsorption Modulator Monolithically Integrated with a Semiconductor Optical Amplifier and a Dual-Waveguide Spot-Size Converter

A semiconductor optical amplifier and electroabsorption modulator monolithically integrated with a spotsize converter input and output is fabricated by means of selective area growth,quantum well intermixing,and asymmetric twin waveguide technology. A 1550-1600nm lossless operation with a high DC extinction ratio of 25dB and more than 10GHz 3dB bandwidth are successfully achieved. The output beam divergence angles of the device in the horizontal and vertical directions are as small as 7.3°× 18.0°, respectively, resulting in a 3.0dB coupling loss with a cleaved single-mode optical fiber.

Experimental comparison between corona and contact poling for EO polymer modulators

Two different poling techniques-corona poling and contact poling in the backdrop of electro-optic （EO） polymer modulators are compared. A 3-layer structure EO polymer modulator is prepared for the poling. The poling setups and procedures of these two different methods are given. It is found that a well-controlled precure step is very critical, otherwise it will result in either lower poling efficiency or damaged film. Experimental results show that contact poling does not create severe surface damage as corona poling and poling voltage is much lower, but corona poling provides higher EO effect than contact poling. Besides, contact poling can provide poling size as large as the substrate size.

Mach-Zehnder Electro-Optic Polymer Modulator with C orona Poled Core Layer

A Mach-Zehnder(MZ) electro-optic(EO) modulator are real iz ed,with three optical layers as polymer materials.The functional layer is the co rona poled crosslinkable polyurethane.The ridge waveguide is fabricated by using the spin-coating,poling,photolithography and oxygen reactive ion etching(RIE) techniques.The mode and the modulation properties of these devices are demonstra ted in a micron control system,while the light source works at the wavelength of 1 31 or 1 55 micron.

High Extinction Ration Polarization Independent EA Modulator

An electro absorption modulator is fabricated for optical network system.The strained InGaAs/InAlAs MQW shows improved modulation properties,including polarization independent,high extinction ratio (>40dB) and low capacitance (<0 5pF),with which,an ultra high frequency(>10GHz) can be obtained.

Monolithic Integration of Electro-Absorption Modulators and DFB Lasers by Modified Double Stack Active Layer Approach

Monolithic electro absorption modulated distributed feedback(DFB) lasers are proposed and fabricated by using a modified double stack active layer.The 38mA threshold,9dB extinction ratio (from 0 5V to 3 0V),and about 5mW output power at the 100mA operation current are achieved.Compared with other reported results (only 1 5mW at the same operation current) of the traditional stack active structure,the proposed structure improves the output power of devices.