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...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.展开更多
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...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.展开更多
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...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.展开更多
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 neuromodu...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.展开更多
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...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.展开更多
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 sh...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.展开更多
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,decipherin...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.展开更多
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 con...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.展开更多
We report broadband all-fiber optical phase modulation based on the photo-thermal effect in a gas-filled hollow-core fiber.The phase modulation dynamics are studied by multi-physics simulation.A phase modulator is fab...We report broadband all-fiber optical phase modulation based on the photo-thermal effect in a gas-filled hollow-core fiber.The phase modulation dynamics are studied by multi-physics simulation.A phase modulator is fabricated using a 5.6-cm-long anti-resonant hollow-core fiber with pure acetylene filling.It has a half-wave optical power of 289 mW at 100 kHz and an average insertion loss 0.6 dB over a broad wavelength range from 1450 to 1650 nm.The rise and fall time constants are 3.5 and 3.7μs,respectively,2–3 orders of magnitude better than the previously reported microfiber-based photo-thermal phase modulators.The gas-filled hollow-core waveguide configuration is promising for optical phase modulation from ultraviolet to mid-infrared which is challenging to achieve with solid optical fibers.展开更多
Spatial light modulators,as dynamic flat-panel optical devices,have witnessed rapid development over the past two decades,concomitant with the advancements in micro-and opto-electronic integration technology.In partic...Spatial light modulators,as dynamic flat-panel optical devices,have witnessed rapid development over the past two decades,concomitant with the advancements in micro-and opto-electronic integration technology.In particular,liquid-crystal spatial light modulator(LC-SLM)technologies have been regarded as versatile tools for generating arbitrary optical fields and tailoring all degrees of freedom beyond just phase and amplitude.These devices have gained significant interest in the nascent field of structured light in space and time,facilitated by their ease of use and real-time light manipulation,fueling both fundamental research and practical applications.Here we provide an overview of the key working principles of LC-SLMs and review the significant progress made to date in their deployment for various applications,covering topics as diverse as beam shaping and steering,holography,optical trapping and tweezers,measurement,wavefront coding,optical vortex,and quantum optics.Finally,we conclude with an outlook on the potential opportunities and technical challenges in this rapidly developing field.展开更多
Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic th...Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.展开更多
To enhance the output torque and minimize the torque ripple of coaxial magnetic gear(CMG),a novel auxiliary flux modulator CMG with unequal magnetic poles is proposed.This design incorporates an inner rotor with an as...To enhance the output torque and minimize the torque ripple of coaxial magnetic gear(CMG),a novel auxiliary flux modulator CMG with unequal magnetic poles is proposed.This design incorporates an inner rotor with an asymmetric sector and a trapezoidal combined N-S pole structure,featuring Halbach arrays for the arrangement of permanent magnets(PMs).The outer rotor PMs adopt a Spoke-type configuration.To optimize the CMG for high output torque and low torque ripple,a sensitivity analysis is conducted to identify key size parameters that significantly influence the optimization objectives.Based on the sensitivity hierarchy of these parameters,a multi-objective optimization analysis is performed using a genetic algorithm(GA)to determine the optimal structural parameter values of the CMG.In addition,a coaxial magnetic gear(CMG)topology with 4 inner and 17 outer pole pairs is adopted,and the parametric model is established.Finally,the electromagnetic properties of the CMG are evaluated using the finite element method.The results indicate a remarkable reduction in torque ripple,specifically by 46.15%.展开更多
Waveguide-integrated optical modulators are indispensable for on-chip optical interconnects and optical computing.To cope with the ever-increasing amount of data being generated and consumed,ultrafast waveguide-integr...Waveguide-integrated optical modulators are indispensable for on-chip optical interconnects and optical computing.To cope with the ever-increasing amount of data being generated and consumed,ultrafast waveguide-integrated optical modulators with low energy consumption are highly demanded.In recent years,two-dimensional(2D)materials have attracted a lot of attention and have provided tremendous opportunities for the development of high-performance waveguide-integrated optical modulators because of their extraordinary optoelectronic properties and versatile compatibility.This paper reviews the state-of-the-art waveguide-integrated optical modulators with 2D materials,providing researchers with the developing trends in the field and allowing them to identify existing challenges and promising potential solutions.First,the concept and fundamental mechanisms of optical modulation with 2D materials are summarized.Second,a review of waveguide-integrated optical modulators employing electro-optic,all-optic,and thermo-optic effects is provided.Finally,the challenges and perspectives of waveguide-integrated modulators with 2D materials are discussed.展开更多
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...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.展开更多
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-OS...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.展开更多
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...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.展开更多
Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatm...Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.展开更多
Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer...Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.展开更多
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 ...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.展开更多
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 asymm...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.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No.52106099)the Natural Science Foundation of Shandong Province of China (Grant No.ZR2022YQ57)the Taishan Scholars Program。
文摘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.
基金supported by the Guangdong Major Project of Basic and Applied Basic Research(Grant No.2020B0301030009)the National Key Research and Development Program of China(Grant No.2022YFA1604304)the National Natural Science Foundation of China(Grant No.92250305).
文摘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.
基金supported by funds from the Italian Ministry of Health,Ricerca Finalizzata,(Grant N.GR-2013-02355882 and GR-2021-12373946 to AL)5x1000 Project of the Istituto Superiore di Sanità(Project code:ISS5x1000_21-949432e8c9be to AL)the European Union–NextGeneration EU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”to EA(CUP I83C22001830006)。
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China (U2031210 and 11827804)Science Research from the China Manned Space Project (CMS-CSST-2021-A11 and CMS-CSST-2021-B04).
文摘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.
文摘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.
基金Supported by the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘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.
基金The research that yielded these results,was funded by the Belgian Federal Public Service of Health,Food Chain Safety and Environment through the contract RF 17/6314 LactoPigHealthMatthias Dierick is supported by the Flemish fund for scientific research(FWO3S036319).
文摘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.
基金We are grateful for financial supports from the National Key Research and Development Program of China(2019YFB2203904)the National Natural Science Foundation of China(U21A20506,62105122,61827820,62005233)+1 种基金the Shenzhen STIC Funding(RCBS20200714114819032)the Local Innovative and Research Teams Project of Guangdong Pear River Talents Program(2019BT02X105).
文摘We report broadband all-fiber optical phase modulation based on the photo-thermal effect in a gas-filled hollow-core fiber.The phase modulation dynamics are studied by multi-physics simulation.A phase modulator is fabricated using a 5.6-cm-long anti-resonant hollow-core fiber with pure acetylene filling.It has a half-wave optical power of 289 mW at 100 kHz and an average insertion loss 0.6 dB over a broad wavelength range from 1450 to 1650 nm.The rise and fall time constants are 3.5 and 3.7μs,respectively,2–3 orders of magnitude better than the previously reported microfiber-based photo-thermal phase modulators.The gas-filled hollow-core waveguide configuration is promising for optical phase modulation from ultraviolet to mid-infrared which is challenging to achieve with solid optical fibers.
基金supports from National Natural Science Foundation of China (No.62235009).
文摘Spatial light modulators,as dynamic flat-panel optical devices,have witnessed rapid development over the past two decades,concomitant with the advancements in micro-and opto-electronic integration technology.In particular,liquid-crystal spatial light modulator(LC-SLM)technologies have been regarded as versatile tools for generating arbitrary optical fields and tailoring all degrees of freedom beyond just phase and amplitude.These devices have gained significant interest in the nascent field of structured light in space and time,facilitated by their ease of use and real-time light manipulation,fueling both fundamental research and practical applications.Here we provide an overview of the key working principles of LC-SLMs and review the significant progress made to date in their deployment for various applications,covering topics as diverse as beam shaping and steering,holography,optical trapping and tweezers,measurement,wavefront coding,optical vortex,and quantum optics.Finally,we conclude with an outlook on the potential opportunities and technical challenges in this rapidly developing field.
文摘Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.
文摘To enhance the output torque and minimize the torque ripple of coaxial magnetic gear(CMG),a novel auxiliary flux modulator CMG with unequal magnetic poles is proposed.This design incorporates an inner rotor with an asymmetric sector and a trapezoidal combined N-S pole structure,featuring Halbach arrays for the arrangement of permanent magnets(PMs).The outer rotor PMs adopt a Spoke-type configuration.To optimize the CMG for high output torque and low torque ripple,a sensitivity analysis is conducted to identify key size parameters that significantly influence the optimization objectives.Based on the sensitivity hierarchy of these parameters,a multi-objective optimization analysis is performed using a genetic algorithm(GA)to determine the optimal structural parameter values of the CMG.In addition,a coaxial magnetic gear(CMG)topology with 4 inner and 17 outer pole pairs is adopted,and the parametric model is established.Finally,the electromagnetic properties of the CMG are evaluated using the finite element method.The results indicate a remarkable reduction in torque ripple,specifically by 46.15%.
基金funding support from the National Major Research and Development Program(2019YFB2203603)the National Science Fund for Distinguished Young Scholars(61725503)+2 种基金the National Natural Science Foundation of China(NSFC)(62275273,11804387,and 91950205)the China Postdoctoral Science Foundation(2020M681847)the Zhejiang Provincial Natural Science Foundation(LZ18F050001).
文摘Waveguide-integrated optical modulators are indispensable for on-chip optical interconnects and optical computing.To cope with the ever-increasing amount of data being generated and consumed,ultrafast waveguide-integrated optical modulators with low energy consumption are highly demanded.In recent years,two-dimensional(2D)materials have attracted a lot of attention and have provided tremendous opportunities for the development of high-performance waveguide-integrated optical modulators because of their extraordinary optoelectronic properties and versatile compatibility.This paper reviews the state-of-the-art waveguide-integrated optical modulators with 2D materials,providing researchers with the developing trends in the field and allowing them to identify existing challenges and promising potential solutions.First,the concept and fundamental mechanisms of optical modulation with 2D materials are summarized.Second,a review of waveguide-integrated optical modulators employing electro-optic,all-optic,and thermo-optic effects is provided.Finally,the challenges and perspectives of waveguide-integrated modulators with 2D materials are discussed.
文摘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.
文摘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.
文摘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.
文摘Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.
基金supported by FIS/IMSS project No.FIS/IMSS/PROT/G13/1216CGA received Beca de Excelencia en Investigación by Fundación IMSS,ACS+1 种基金JJSU received financial support from CIS/IMSSCONACy T,RPA received financial support from USC-CONACYT Postdoctoral Scholars Program
文摘Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.
文摘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.
文摘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.
