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.

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.

High photoelectric conversion efficiency and fast relaxation time of FA_(0.4)MA_(0.6)PbI_(3) applied in ultrafast modulation of terahertz waves

Active control of terahertz(THz)waves is attracting tremendous attentions in terahertz communications and active photonic devices.Perovskite,due to its excellent photoelectric conversion performance and simple manufacturing process,has emerged as a promising candidate for optoelectronic applications.However,the exploration of perovskites in optically controlled THz modulators is still limited.In this work,the photoelectric properties and carrier dynamics of FA_(0.4)MA_(0.6)PbI_(3)perovskite films were investigated by optical pumped terahertz probe(OPTP)system.The ultrafast carrier dynamics reveal that FA_(0.4)MA_(0.6)PbI_(3)thin film exhibits rapid switching and relaxation time within picosecond level,suggesting that FA_(0.4)MA_(0.6)PbI_(3)is an ideal candidate for active THz devices with ultrafast response.Furthermore,as a proof of concept,a FA_(0.4)MA_(0.6)PbI_(3)-based metadevice with integrating plasma-induced transparency(PIT)effect was fabricated to achieve ultrafast modulation of THz wave.The experimental results demonstrated that the switching time of FA_(0.4)MA_(0.6)PbI_(3)-based THz modulator is near to 3.5 ps,and the threshold of optical pump is as low as 12.7μJ cm^(-2).The simulation results attribute the mechanism of ultrafast THz modulation to photo-induced free carriers in the FA_(0.4)MA_(0.6)PbI_(3)layer,which progressively shorten the capacitive gap of PIT resonator.This study not only illuminates the potential of FA_(0.4)MA_(0.6)PbI_(3)in THz modulation,but also contributes to the field of ultrafast photonic devices.

An 80dB Dynamic Range ΣΔ Modulator for Low-IF GSM Receivers

A high-resolution,200kHz signal bandwidth,third-order single-loop single-bit ε△ modulator used in low-IF GSM receivers is presented. The modulator is implemented with fully differential switched capacitor circuits in standard 0. 6μm 2P2M CMOS technology. The modulator uses two balanced reference voltages of ±1V,and is driven by a single 26MHz clock signal. The measurement results show that,with an oversampling ratio of 64, the modulator achieves an 80.6dB dynamic range,a 71.8dB peak SNDR,and a 73.9dB peak SNR in the signal bandwidth of 200kHz. The modulator dissipates 15mW static power from a single 5V supply.

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.

Combining cytochrome P-450 3A4 modulators and cyclosporine or everolimus in transplantation is successful

AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observational clinical trial in low immunologic risk patients who, after signing an Institutional Review Board approved consent form, were included in one of two groups. The first one(n = 59) received everolimus(target blood level, 3-8 ng/m L) and the other(n = 114) azathioprine 2 mg/kg per day or mycophenolate mofetyl(MMF) 2 g/d. Both groups also received tapering steroids, the cytochrome P-450 3A4(CYP3A4) modulator, ketoconazole 50-100 mg/d, and cyclosporine with C0 targets in the everolimus group of 200-250 ng/mL in 1 mo, 100-125 ng/m L in 2 mo, and 50-65 ng/m L thereafter, and in the azathioprine or MMF group of 250-300 ng/mL in 1 mo, 200-250 ng/mL in 2 mo, 180-200 ng/m L until 3-6 mo, and 100-125 ng/mL thereafter. Clinical visits were performed monthly the first year and quarterly thereafter by treating physicians and all data was extracted by the investigators.RESULTS: The clinical characteristics of these two cohorts were similar. During the follow up(66 + 31 mo), both groups showed comparable clinical courses, but the biopsy proven acute rejection rate during the full follow-up period seemed to be lower in the everolimus group(20% vs 36%; P = 0.04). The everolimus group did not show a higher surgical complication rate thanthe other group. By the end of the follow-up period, the everolimus group tended to show a higher glomerular filtration rate. Nevertheless, we found no evidence of a consistent negative slope of the temporal allograft function estimated by the modification of the diet in renal disease formula in any of both groups. At 6 years of follow-up, the uncensored and death-censored graft survivals were 91% and 93%, and 91% and 83% in the everolimus plus cyclosporine, and cyclosporine alone groups, respectively. The addition of ketoconazole saved 80% of cyclosporine and 56% of everolimus doses. CONCLUSION: Combining CYP3A4 modulators with CNI or mammalian target of rapamycin inhibitor, in low immunological risk kidney transplant recipients is feasible, effective, safe and affordable even in the long term.

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.

High Performance Optical Modulator and Detector for 100 Gb/s Transmission System

Silicon photonics, one of the most promising candidates forbreaking the bottleneck of current optical transmission systems, has been developing rapidly in both performance andmaturity. The analysis and design of the two key componentsof this technology, the optical modulator and detector, are presented in this paper. The Mach-Zehnder modulator with Utype PN junction is optimized to obtain the modulation efficiency of 0.559 V·cm. The electro-optical 3 dB bandwidth ofthis device is 30 GHz. The simulation of the PIN waveguideSi based Ge photodetector at 1.55 μm wavelength is also presented. The device shows a very low dark current of about 10 nA-at1 V, and the obtained responsivity and 3 dB bandwidth are appreciable. These results practically meet the requirement of commercial 100 Gb/s optical transmission systems.

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.

Light-modulated graphene-based φ_(0) Josephson junction and -φ_(0) to φ_(0) transition

We investigate the chiral edge states-induced Josephson current–phase relation in a graphene-based Josephson junction modulated by the off-resonant circularly polarized light and the staggered sublattice potential.By solving the Bogoliubov–de Gennes equation,a φ_(0) Josephson junction is induced in the coaction of the off-resonant circularly polarized light and the staggered sublattice potential,which arises from the fact that the center of-mass wave vector of Cooper pair becomes finite and the opposite center of-mass wave vector to compensate is lacking in the nonsuperconducting region.Interestingly,when the direction of polarization of light is changed,-φ_(0) to φ_(0) transition generates,which generalizes the concept of traditional 0–πtransition.Our findings provide a purely optical way to manipulate a phase-controllable Josephson device and guidelines for future experiments to confirm the presence of graphene-based φ_(0)Josephson junction.

2.4Gb/s,50Km Optical Fiber Transmission Using Ti:LiNbO_3 External Modulator

2.488 Gb/s optical fiber transmission experiment using a domestic Ti.LiNbO3 externalmodulator was demonstrated for the first time in China.A receiver sensitivity of -30.3dBmwas obtained at a BER of 10-10after transmission through 50.7 km conventional single modefiber.

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.

Design of 150kV bouncer modulator

The 150 kV bouncer modulator is designed to drive the 10 MW multi-beam klystron for the DESYTESLA Test Facility. The modulator is different from the 10 kV modulators previously built at Fermilab. First, thenew 150 kV bouncer modulator has no transformer, so the modulator circuit is simplified and the output waveform isimproved well. Second, the bouncer circuit has been changed to fit the output need, which is the most significantchallenge. This paper gives the design of the 150 kV long pulse bouncer modulator.

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.

Performance and Optimization of 10 Gb/s Electroabsorption Modulator in Short Transmission

Transmission performance of electroabsorption modulator in 10 Gb/s transmission systems has been simulated and analyzed under the condition of taking into account the chirp,extinction ratio, transmissivity and rise/fall time.Results show that short transmission distance without EDFA after EAM can be used in future metropolitan area network,but the transmissivity must be carefully considered. The sampling time range and decision level can be optimized to reduce the bit error ratio.

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.