Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of ...Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO.This study focuses on the ability of the collagen receptor,discoidin domain receptor 2(DDR2),to regulate BMP activity.As will be shown,induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice.In addition,Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva.In cells migrating into BMP2 implants,DDR2 is co-expressed with GLI1,a skeletal stem cell marker,and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages.Consistent with this distribution,conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals.This response was explained by selective inhibition of Gli1+cell proliferation without changes in apoptosis.The basis for this DDR2 requirement was explored further using bone marrow stromal cells.Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo,bone formation,early BMP responses including SMAD phosphorylation remained largely intact.Instead,Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates,YAP and TAZ.This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix,which subsequently affect BMP responsiveness.In summary,DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.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
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
Femtosecond laser processing is an important machining method for micro-optical components such as Fresnel zone plate(FZP).However,the low processing efficiency of the femtosecond laser restricts its application.Here,...Femtosecond laser processing is an important machining method for micro-optical components such as Fresnel zone plate(FZP).However,the low processing efficiency of the femtosecond laser restricts its application.Here,a femtosecond laser Bessel beam is proposed to process micro-FZP,which is modulated from a Gaussian beam to a Bessel annular beam.The processing time for FZP with an outer diameter of 60μm is reduced from 30 min to 1.5 min on an important semiconductor material gallium arsenide(GaAs),which significantly improves the processing efficiency.In the modulation process,a central ablation hole that has an adverse effect on the diffraction performance is produced,and the adverse effect is eliminated by superimposing the blazed grating hologram.Meanwhile,the FZP machined by spatial light modulator(SLM)has good morphology and higher diffraction efficiency,which provides a strong guarantee for the application of micro-FZP in computed tomography and solar photovoltaic cells.展开更多
Through active manipulation of wavelengths,a structure exposed to a water-wave field can achieve a target hydrodynamic performance.Based on the form invariance of the governing equation for shallow water waves,wavelen...Through active manipulation of wavelengths,a structure exposed to a water-wave field can achieve a target hydrodynamic performance.Based on the form invariance of the governing equation for shallow water waves,wavelength modulators have been proposed using the space transformation method,which enables wavelength manipulation by distributing an anisotropic medium that incorporates water depth and gravitational acceleration within the modulation space.First,annular wavelength modulators were designed using the space transformation method to reduce or amplify the wavelength of shallow water waves.The control method of wavelength scaling ratios was investigated.In addition to plane waves,the wavelength modulator was applied to manipulate the wavelength of cylindrical waves.Furthermore,the interactions between a vertical cylinder and modulated water waves were studied.Results indicate that the wavelength can be arbitrarily reduced or amplified by adjusting the dimensional parameters of the modulator.Additionally,the modulator is effective for plane waves and cylindrical waves.This wavelength modulator can enable the structure to achieve the desired scattering characteristics at the target wavelength.展开更多
With the continuous improvement of signal processing accuracy requirements in modern electronic systems,the demand for high-precision analog-to-digital converters(ADCs)is increasing.Sigma-Delta modulator,as the most i...With the continuous improvement of signal processing accuracy requirements in modern electronic systems,the demand for high-precision analog-to-digital converters(ADCs)is increasing.Sigma-Delta modulator,as the most important component of high-precision ADC,is widely used in high-quality audio,high-precision instrument measurement,and other fields due to its advantages of high precision,strong noise resistance,and low hardware cost.This article designs a discrete structure third-order four-bit high-precision Sigma-Delta modulator through modeling,with an oversampling rate set to 512.Under ideal conditions,the simulation results show that the SDNR reaches 152.7db and the ENOB is 25.24bits.After introducing non-ideal noise,the system performance has decreased.The simulation results show that the SDNR is as high as 124.5db and the ENOB is 20.39bits.This indicates that the design can achieve high-precision conversion and provide assistance for further research in the future.展开更多
As the demand for computing power in data centers continues to grow, balancing data transmitting speed and energy efficiency has emerged as a critical challenge. Highbandwidth, low-power interconnection schemes are in...As the demand for computing power in data centers continues to grow, balancing data transmitting speed and energy efficiency has emerged as a critical challenge. Highbandwidth, low-power interconnection schemes are increasingly recognized as core requirements for next-generation intelligent computing center designs^([1, 2]). For short-range optical interconnections of intra-chip and inter-chip—typically covering tens of meters or less—microring resonant modulators (MRM) are emerging as an ideal solution.展开更多
Based on previous experience,learning to avoid or seek certain specific stimuli again in the future is crucial for survival.Our brains are wired to assign a particular valence-either positive or negativeas a result of...Based on previous experience,learning to avoid or seek certain specific stimuli again in the future is crucial for survival.Our brains are wired to assign a particular valence-either positive or negativeas a result of sensory stimuli,and it is this valence that serves as the foundational motivation for our subsequent actions.Simply put,all motivational actions fall into two categories:pleasure-seeking behavior guided by positive emotional valence,and pain-avoiding behavior driven by negative emotional valence[1].The ability to shift from one emotional valence to another is an important characteristic of affective states,while the instability of emotional states underlies many psychiatric disorders,highlighting the clinical importance of managing and understanding these fluctuations.This ability to adapt emotional responses can be attained by modulating the gain across distinct neural pathways,thus enabling the nuanced and smooth assignment of valence through the strengthening or weakening of circuit activity[1,2].展开更多
In this paper,we present a novel first-order digitalΣΔconverter tailored for digital-to-analog applications,focusing on achieving both high yield and reduced silicon estate.Our approach incorporates a substantial le...In this paper,we present a novel first-order digitalΣΔconverter tailored for digital-to-analog applications,focusing on achieving both high yield and reduced silicon estate.Our approach incorporates a substantial level of dithering noise into the input signal,strategically aimed at mitigating the spurious frequencies commonly encountered in such converters.Validation of our design is performed through simulations using a high-level simulator specialized in mixed-signal circuit analysis.The results underscore the enhanced performance of our circuit,especially in reducing spurious frequencies,highlighting its efficiency and effectiveness.The final circuit exhibits an effective number of bits of 13.展开更多
Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian cloc...Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.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
Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis ind...Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.展开更多
Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturat...Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases.While extensively studied in asthma,its role in non-respiratory allergic conditions such as atopic dermatitis(AD)and allergic rhinitis(AR)remains comparatively underexplored.This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR.In AD,vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis,and enhances antimicrobial defense via induction of antimicrobial peptides.Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children,particularly those with allergic sensitization.Select randomized controlled trials suggest clinical improvement with supplementation,especially at doses>2000 IU/day in deficient individuals.In AR,epidemiological data indicate stronger inverse associations with seasonal(pollen-induced)disease.Proposed mechanisms include modulation of dendritic cells,regulatory T cells,T helper 2 cytokines,and mucosal barrier integrity.The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance.Although promising,clinical evidence remains heterogeneous.Future research should prioritize phenotype-stratified trials to clarify optimal dosing,timing,and individual response determinants,including genetics and microbiome composition.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
High performance electro-optic modulator,as the key device of integrated ultra-wideband optical systems,have be-come the focus of research.Meanwhile,the organic-based hybrid electro-optic modulators,which make full us...High performance electro-optic modulator,as the key device of integrated ultra-wideband optical systems,have be-come the focus of research.Meanwhile,the organic-based hybrid electro-optic modulators,which make full use of the advant-ages of organic electro-optic(OEO)materials(e.g.high electro-optic coefficient,fast response speed,high bandwidth,easy pro-cessing/integration and low cost)have attracted considerable attention.In this paper,we introduce a series of high-perform-ance OEO materials that exhibit good properties in electro-optic activity and thermal stability.In addition,the recent progress of organic-based hybrid electro-optic devices is reviewed,including photonic crystal-organic hybrid(PCOH),silicon-organic hy-brid(SOH)and plasmonic-organic hybrid(POH)modulators.A high-performance integrated optical platform based on OEO ma-terials is a promising solution for growing high speeds and low power consumption in compact sizes.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supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
基金Scientific Research Training Program for Young Talents of Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(F.W.),NIH/NIDCR grants DE029012 and DE029465Department of Defense Grant PR190899(R.T.F.)Michigan Musculoskeletal Health Core Center(NIH/NIAMS P30 AR069620)。
文摘Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO.This study focuses on the ability of the collagen receptor,discoidin domain receptor 2(DDR2),to regulate BMP activity.As will be shown,induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice.In addition,Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva.In cells migrating into BMP2 implants,DDR2 is co-expressed with GLI1,a skeletal stem cell marker,and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages.Consistent with this distribution,conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals.This response was explained by selective inhibition of Gli1+cell proliferation without changes in apoptosis.The basis for this DDR2 requirement was explored further using bone marrow stromal cells.Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo,bone formation,early BMP responses including SMAD phosphorylation remained largely intact.Instead,Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates,YAP and TAZ.This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix,which subsequently affect BMP responsiveness.In summary,DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.
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 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.
基金Projects(51875584,51875585,51975590)supported by the National Natural Science Foundation of China。
文摘Femtosecond laser processing is an important machining method for micro-optical components such as Fresnel zone plate(FZP).However,the low processing efficiency of the femtosecond laser restricts its application.Here,a femtosecond laser Bessel beam is proposed to process micro-FZP,which is modulated from a Gaussian beam to a Bessel annular beam.The processing time for FZP with an outer diameter of 60μm is reduced from 30 min to 1.5 min on an important semiconductor material gallium arsenide(GaAs),which significantly improves the processing efficiency.In the modulation process,a central ablation hole that has an adverse effect on the diffraction performance is produced,and the adverse effect is eliminated by superimposing the blazed grating hologram.Meanwhile,the FZP machined by spatial light modulator(SLM)has good morphology and higher diffraction efficiency,which provides a strong guarantee for the application of micro-FZP in computed tomography and solar photovoltaic cells.
基金supported by National Key R&D Program of China(2022YFC3104200)the China Postdoctoral Science Foundation(2023M742157)+3 种基金the Shandong Province Taishan Scholars Project(tsqn201909172)the Shandong Provincial Natural Science Foundation(ZR2023QA097)the Open Research Fund Program of State Key Laboratory of Coastal and Offshore Engineering,Dalian University of Technology(LP2309)the Innovation Project of Qingdao Post-Doctoral(QDBSH20230202121).
文摘Through active manipulation of wavelengths,a structure exposed to a water-wave field can achieve a target hydrodynamic performance.Based on the form invariance of the governing equation for shallow water waves,wavelength modulators have been proposed using the space transformation method,which enables wavelength manipulation by distributing an anisotropic medium that incorporates water depth and gravitational acceleration within the modulation space.First,annular wavelength modulators were designed using the space transformation method to reduce or amplify the wavelength of shallow water waves.The control method of wavelength scaling ratios was investigated.In addition to plane waves,the wavelength modulator was applied to manipulate the wavelength of cylindrical waves.Furthermore,the interactions between a vertical cylinder and modulated water waves were studied.Results indicate that the wavelength can be arbitrarily reduced or amplified by adjusting the dimensional parameters of the modulator.Additionally,the modulator is effective for plane waves and cylindrical waves.This wavelength modulator can enable the structure to achieve the desired scattering characteristics at the target wavelength.
文摘With the continuous improvement of signal processing accuracy requirements in modern electronic systems,the demand for high-precision analog-to-digital converters(ADCs)is increasing.Sigma-Delta modulator,as the most important component of high-precision ADC,is widely used in high-quality audio,high-precision instrument measurement,and other fields due to its advantages of high precision,strong noise resistance,and low hardware cost.This article designs a discrete structure third-order four-bit high-precision Sigma-Delta modulator through modeling,with an oversampling rate set to 512.Under ideal conditions,the simulation results show that the SDNR reaches 152.7db and the ENOB is 25.24bits.After introducing non-ideal noise,the system performance has decreased.The simulation results show that the SDNR is as high as 124.5db and the ENOB is 20.39bits.This indicates that the design can achieve high-precision conversion and provide assistance for further research in the future.
基金supported by the National Natural Science Foundation of China (Grant Nos. 61925505 and 62405070)"Pioneer" and "Leading Goose" R&D Program of Zhejiang Province (Grant No. 2024C01112)National Key Research and Development Program of China (Grant No. 2023YFB2807100)。
文摘As the demand for computing power in data centers continues to grow, balancing data transmitting speed and energy efficiency has emerged as a critical challenge. Highbandwidth, low-power interconnection schemes are increasingly recognized as core requirements for next-generation intelligent computing center designs^([1, 2]). For short-range optical interconnections of intra-chip and inter-chip—typically covering tens of meters or less—microring resonant modulators (MRM) are emerging as an ideal solution.
基金supported by grants from the Key-Area Research and Development Program of Guangdong province(2019B030335001)the National Natural Science Foundation of China(32200815)the China Postdoctoral Science Foundation(2022M721218).
文摘Based on previous experience,learning to avoid or seek certain specific stimuli again in the future is crucial for survival.Our brains are wired to assign a particular valence-either positive or negativeas a result of sensory stimuli,and it is this valence that serves as the foundational motivation for our subsequent actions.Simply put,all motivational actions fall into two categories:pleasure-seeking behavior guided by positive emotional valence,and pain-avoiding behavior driven by negative emotional valence[1].The ability to shift from one emotional valence to another is an important characteristic of affective states,while the instability of emotional states underlies many psychiatric disorders,highlighting the clinical importance of managing and understanding these fluctuations.This ability to adapt emotional responses can be attained by modulating the gain across distinct neural pathways,thus enabling the nuanced and smooth assignment of valence through the strengthening or weakening of circuit activity[1,2].
文摘In this paper,we present a novel first-order digitalΣΔconverter tailored for digital-to-analog applications,focusing on achieving both high yield and reduced silicon estate.Our approach incorporates a substantial level of dithering noise into the input signal,strategically aimed at mitigating the spurious frequencies commonly encountered in such converters.Validation of our design is performed through simulations using a high-level simulator specialized in mixed-signal circuit analysis.The results underscore the enhanced performance of our circuit,especially in reducing spurious frequencies,highlighting its efficiency and effectiveness.The final circuit exhibits an effective number of bits of 13.
基金supported in part by grants from the National Key R&D Program of China(2021YFC2400400/04 to L.L.C.)the National Natural Science Foundation of China for Key Program Projects(82030070 to L.L.C.)+2 种基金the National Natural Science Foundation of China for Distinguished Young Scholars(22025102 to Q.W.)the National Natural Science Foundation of China(82271036 to Y.F.W.,22277033 to J.Z.,22177034 to L.K.M.)the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001 to Y.F.W.)。
文摘Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.
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Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.
文摘Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases.While extensively studied in asthma,its role in non-respiratory allergic conditions such as atopic dermatitis(AD)and allergic rhinitis(AR)remains comparatively underexplored.This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR.In AD,vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis,and enhances antimicrobial defense via induction of antimicrobial peptides.Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children,particularly those with allergic sensitization.Select randomized controlled trials suggest clinical improvement with supplementation,especially at doses>2000 IU/day in deficient individuals.In AR,epidemiological data indicate stronger inverse associations with seasonal(pollen-induced)disease.Proposed mechanisms include modulation of dendritic cells,regulatory T cells,T helper 2 cytokines,and mucosal barrier integrity.The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance.Although promising,clinical evidence remains heterogeneous.Future research should prioritize phenotype-stratified trials to clarify optimal dosing,timing,and individual response determinants,including genetics and microbiome composition.
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.
基金the National Natural Science Foundation of China(No.62175267)the Beijing Municipal Natural Science Foundation(No.4192061)+1 种基金the Fundamental Research Funds for the Central Universities(2020MDJC13)the Beijing Talents Foundation(2018000021223ZK45)for the financial support.
文摘High performance electro-optic modulator,as the key device of integrated ultra-wideband optical systems,have be-come the focus of research.Meanwhile,the organic-based hybrid electro-optic modulators,which make full use of the advant-ages of organic electro-optic(OEO)materials(e.g.high electro-optic coefficient,fast response speed,high bandwidth,easy pro-cessing/integration and low cost)have attracted considerable attention.In this paper,we introduce a series of high-perform-ance OEO materials that exhibit good properties in electro-optic activity and thermal stability.In addition,the recent progress of organic-based hybrid electro-optic devices is reviewed,including photonic crystal-organic hybrid(PCOH),silicon-organic hy-brid(SOH)and plasmonic-organic hybrid(POH)modulators.A high-performance integrated optical platform based on OEO ma-terials is a promising solution for growing high speeds and low power consumption in compact sizes.
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.
