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.

Design of Serially Concatenated Two-Level Polar Coded Modulation System with Low-Complexity

Multilevel coding(MLC)is a commonly used polar coded modulation scheme,but challenging to implement in engineering due to its high complexity and long decoding delay for high-order modulations.To address these limitations,a novel two-level serially concatenated MLC scheme,in which the bitlevels with similar reliability are bundled and transmitted together,is proposed.The proposed scheme hierarchically protects the two bit-level sets:the bitlevel sets at the higher level are sufficiently reliable and do not require excessive resources for protection,whereas only the bit-level sets at the lower level are encoded by polar codes.The proposed scheme has the advantages of low power consumption,low delay and high reliability.Moreover,an optimized constellation signal labeling rule that can enhance the performance is proposed.Finally,the superiority of the proposed scheme is validated through the theoretical analysis and simulation results.Compared with the bit interleaving coding modulation(BICM)scheme,under 256-quadrature amplitude modulation(QAM),the proposed scheme attains a performance gain of 1.0 dB while reducing the decoding complexity by 54.55%.

Optimization strategies for operational parameters of Rydberg atom-based amplitude modulation receiver

The Rydberg atom-based receiver, as a novel type of antenna, demonstrates broad application prospects in the field of microwave communications. However, since Rydberg atomic receivers are nonlinear systems, mismatches between the parameters of the received amplitude modulation(AM) signals and the system's linear workspace and demodulation operating points can cause severe distortion in the demodulated signals. To address this, the article proposes a method for determining the operational parameters based on the mean square error(MSE) and total harmonic distortion(THD) assessments and presents strategies for optimizing the system's operational parameters focusing on linear response characteristics(LRC) and linear dynamic range(LDR). Specifically, we employ a method that minimizes the MSE to define the system's linear workspace, thereby ensuring the system has a good LRC while maximizing the LDR. To ensure that the signal always operates within the linear workspace, an appropriate carrier amplitude is set as the demodulation operating point. By calculating the THD at different operating points, the LRC performance within different regions of the linear workspace is evaluated, and corresponding optimization strategies based on the range of signal strengths are proposed. Moreover, to more accurately restore the baseband signal, we establish a mapping relationship between the carrier Rabi frequency and the transmitted power of the probe light, and optimize the slope of the linear demodulation function to reduce the MSE to less than 0.8×10^(-4). Finally, based on these methods for determining the operational parameters, we explore the effects of different laser Rabi frequencies on the system performance, and provide optimization recommendations. This research provides robust support for the design of high-performance Rydberg atom-based AM receivers.

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.

Taming of trinitromethyl-oxadiazole to access high density and high oxygen balance via a dual modulation strategy

Energetic compounds bearing the trinitromethyl group are garnering broad attraction as potential candidates for a new generation of high energy dense oxidizers.In this work,an effective dual modulation strategy involving both molecular isomerization and crystal morphology control was employed to design and optimize trinitromethyl-oxadiazole with improved comprehensive performance.Utilizing this dual strategy,3,5-bis(trinitromethyl)-1,2,4-oxadiazole(3)was synthesized,resulting in the formation of two distinct crystal morphologies(needle and sheet)corresponding to two crystal forms(3-a and3-b).Encouragingly,while maintaining ultra-high oxygen balance(21.73%),3 achieves impressive densities(1.97-1.98 g/cm^(3)).To our knowledge,the density of 1.98 g/cm^(3)for 3-a sets a new record among that of nitrogen-rich monocyclic compounds.Notably,practical crystal morphology prediction was creatively introduced to guide the experimental crystallization conditions of 3,increasing the impact sensitivity and friction sensitivity from 1 J to 80 N(3-a)to 10 J and 240 N(3-b),respectively.Additionally,the crystal structural analyses and theoretical calculations were conducted to elucidate the reasons of differences between 3-a and 3-b in density and stability.This work provides an efficient strategy to enhance performance of trinitromethyl derivatives,broadening the path and expanding the toolbox for energetic materials.

A Multi-Task Learning Framework for Joint Sub-Nyquist Wideband Spectrum Sensing and Modulation Recognition

The utilization of millimeter-wave frequencies and cognitive radio(CR)are promising ways to increase the spectral efficiency of wireless communication systems.However,conventional CR spectrum sensing techniques entail sampling the received signal at a Nyquist rate,and they are not viable for wideband signals due to their high cost.This paper expounds on how sub-Nyquist sampling in conjunction with deep learning can be leveraged to remove this limitation.To this end,we propose a multi-task learning(MTL)framework using convolutional neural networks for the joint inference of the underlying narrowband signal number,their modulation scheme,and their location in a wideband spectrum.We demonstrate the effectiveness of the proposed framework for real-world millimeter-wave wideband signals collected by physical devices,exhibiting a 91.7% accuracy in the joint inference task when considering up to two narrowband signals over a wideband spectrum.Ultimately,the proposed data-driven approach enables on-the-fly wideband spectrum sensing,combining accuracy,and computational efficiency,which are indispensable for CR and opportunistic networking.

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.

lncRNA SNHG4 enhanced gastric cancer progression by modulating miR-409-3p/CREB1 axis

Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long non-coding RNAs(lncRNAs)and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies.Studies have shown that the lncRNA small nucleolar RNA host gene 4(SNHG4)serves as a tumor promoter in various malignancies,while its function in GC has yet to be characterized.Therefore,our study aimed to explore the role and underlying mechanism of SNHG4 in GC.Methods:We used qRT-PCR to analyze SNHG4 expression in GC tissues and cells.Kaplan-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC patients.Cellular function experiments such as CCK-8,BrdU,colony formation,flow cytometry analysis,and transwell were performed to explore the effects of SNHG4 on GC cell proliferation,apoptosis,cell cycle,migration,and invasion.We also established xenograft mouse models to explore the effect of SNHG4 on GC tumor growth.Mechanically,dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1(CREB1).Results:The results indicated that SNHG4 was overexpressed in GC tissues and cell lines,and was linked with poor survival rate of GC patients.SNHG4 promoted GC cell proliferation,migration,and invasion while inhibiting cell apoptosis and cell cycle arrest in vitro.The in vivo experiment indicated that SNHG4 facilitated GC tumor growth.Furthermore,SNHG4 was demonstrated to bind to miR-409-3p.Moreover,CREB1 was directly targeted by miR-409-3p.Rescue assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell malignancy.Additionally,miR-409-3p was also revealed to inhibit GC cell proliferation,migration,and invasion by targeting CREB1.Conclusion:In conclusion,we verified that the SNHG4 promoted GC growth and metastasis by binding to miR-409-3p to upregulate CREB1,which may deepen the understanding of the underlying mechanism in GC development.

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.

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.

HD-YOLO:复杂场景下安全帽佩戴检测算法

针对目标密集、有遮挡的复杂施工场景下安全帽佩戴检测存在漏检、误检的问题,提出了一种基于YOLOv8的HD-YOLO安全帽佩戴检测算法。首先,设计了GRC-C2f结构,使用多分支结构捕获多尺度特征,兼顾训练阶段的特征提取能力和推理阶段的计算效率。其次,设计了DSASF颈部结构,结合动态上采样和多尺度特征融合,精准识别和定位图像中的小目标,以提高检测性能。然后,引入Focal Modulation模块替换原有的快速空间金字塔池化(Spatial Pyramid Pooling-Fast,SPPF)结构模块,捕捉图像中的长距离依赖和上下文信息,聚焦于复杂背景中的目标。最后,采用空间增强注意力模块(Spatially Enhanced Attention Module,SEAM)解决小目标遮挡问题。试验结果表明,HD-YOLO算法在同一数据集上平均精度均值为81.8%,相比原始YOLOv8算法提高了5.0百分点。设计的HD-YOLO算法有效提高了复杂场景中佩戴安全帽的检测精度。

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.