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
This paper investigates the design of digital Sigma-Delta Modulator (SDM) for fractional-N frequency synthesizer. Characteristics of SDMs are compared through theory analysis and simulation. The curve of maximum-loop-...This paper investigates the design of digital Sigma-Delta Modulator (SDM) for fractional-N frequency synthesizer. Characteristics of SDMs are compared through theory analysis and simulation. The curve of maximum-loop-bandwidth vs. maximum-phase-noise is suggested to be a new criterion to the performance of SDM,which greatly helps designers to select an appropriate SDM structure to meet their real application requirements and to reduce the cost as low as possible. A low-spur 3-order Mul-tistage Noise Shaping (MASH)-1-1-1 SDM using three 2-bit first-order cascaded modulators is proposed,which balances the requirements of tone-free and maximum operation frequency.展开更多
This paper presents the design and experimental results of a continuous-time (CT) sigma-delta (ΣΔ) modulator with data-weighted average (DWA) technology for WiMAX applications. The proposed modulator comprises a thi...This paper presents the design and experimental results of a continuous-time (CT) sigma-delta (ΣΔ) modulator with data-weighted average (DWA) technology for WiMAX applications. The proposed modulator comprises a third-order active RC loop filter, internal quantizer operating at 160 MHz and three DAC circuits. A multi-bit quantizer is used to increase resolution and multi-bit non-return-to-zero (NRZ) DACs are adopted to reduce clock jitter sensitivity. The NRZ DAC circuits with quantizer excess loop delay compensation are set to be half the sampling period of the quantizer for increasing modulator stability. A dynamic element matching (DEM) technique is applied to multi-bit ΣΔ modulators to improve the nonlinearity of the internal DAC. This approach translates the harmonic distortion components of a nonideal DAC in the feedback loop of a ΣΔ modulator to high-frequency components. Capacitor tuning is utilized to overcome loop coefficient shifts due to process variations. The DWA technique is used for reducing DAC noise due to component mismatches. The prototype is implemented in TSMC 0.18 um CMOS process. Experimental results show that the ΣΔ modulator achieves 54-dB dynamic range, 51-dB SNR, and 48-dB SNDR over a 10-MHz signal bandwidth with an oversampling ratio (OSR) of 8, while dissipating 19.8 mW from a 1.2-V supply. Including pads, the chip area is 1.156 mm2.展开更多
In this paper,in order to reduce power consumption and chip area,as well as to improve the performance of the bandpass sigma-delta modulator,a novel full differential feedforward fourth-order bandpass sigma-delta modu...In this paper,in order to reduce power consumption and chip area,as well as to improve the performance of the bandpass sigma-delta modulator,a novel full differential feedforward fourth-order bandpass sigma-delta modulator was proposed. It used a resonator based on Salo architecture,which employed doublesampling and double-delay technique. The results show that the proposed modulator can achieve lower power consumption and a lower capacitive load than the conventional bandpass modulators on the platform of Simulink. The circuit is implemented with TSMC0. 18 μm CMOS process and operates at a sampling frequency of 20 MHz, 80 MHz effective sampling frequency. Furthermore,it consumes 21. 2 mW from a 1. 8 V supply. The simulated peak signal-to-noise ratio( SNR) is 85. 9 dB and the dynamic range( DR) is 91 dB with 200 kHz bandwidth.展开更多
It is usually difficult to design a high performance Sigma⁃Delta(ΣΔ)modulator due to system noises.In this paper,a disturbance observer(DOB)is utilized to estimate the system noises and eliminate their effects on Σ...It is usually difficult to design a high performance Sigma⁃Delta(ΣΔ)modulator due to system noises.In this paper,a disturbance observer(DOB)is utilized to estimate the system noises and eliminate their effects on ΣΔ modulators.The applied DOB is introduced with a Bode's ideal cut⁃off(BICO)filter used for the Q⁃filter.The proposed DOB with the BICO filter used in ΣΔ modulators can achieve better noise⁃shaping ability,resulting from the less phase loss of the BICO filter.Finally,the simulation results show that the proposed BICO filter scheme is a useful additional tool for improving the performance of ΣΔ modulators.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
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
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
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
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
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
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
This paper introduces a high-revolution,200kHz signal bandwidth EA modulator for low-IF GSM receivers that adopts a 2-1 cascaded single-bit structure to achieve high linearity and stability. Our design is realized in ...This paper introduces a high-revolution,200kHz signal bandwidth EA modulator for low-IF GSM receivers that adopts a 2-1 cascaded single-bit structure to achieve high linearity and stability. Our design is realized in a standard 0.18μm CMOS process with art active area of 0.5mm× 1.1mm.The EA modulator is driven by a single 19.2MHz clock signal and dissipates 5.88mW from 3V power supply. The experimental results show that,with an oversampling ratio of 48, the modulator achieves a 84.4dB dynamic range,73.8dB peak SNDR, and 80dB peak SNR in the signal bandwidth of 200kHz.展开更多
To improve the simulation accuracy of SIMULINK, a novel inclusive behavior model of an integrator is proposed that introduces the effects of different circuit nonidealities of a switched-capacitor sigma-delta modulato...To improve the simulation accuracy of SIMULINK, a novel inclusive behavior model of an integrator is proposed that introduces the effects of different circuit nonidealities of a switched-capacitor sigma-delta modulator into SIMULIK simulation. The nonlinear DC gain and nonlinear settling process are introduced into the op-amp module. The signaldependent charge injection and nonlinear resistance are introduced into the switch module. In addition, the noise source including flicker and thermal noise is introduced into system as an independent module. The novel model is verified by SIMULINK behavioral simulations. The results are compared with results from circuit level simulation in Cadence SPICE using TSMC 0.35μm mixed signal technology. It shows that the novel model succeeds in introducing the influences of the nonidealities into behavior simulation to more realistically describe the circuit performances and increase the accuracy of SIMULINK simulation.展开更多
Traditional feedforward structures suffer from performance constraints caused by the complex adder before quantizer.This paper presents an improved 4th-order 1 -bit sigma-delta modulator which has a simple adder and d...Traditional feedforward structures suffer from performance constraints caused by the complex adder before quantizer.This paper presents an improved 4th-order 1 -bit sigma-delta modulator which has a simple adder and delayed input feedforward to relax timing constraints and implement low-distortion.The modulator was fabricated in a 0.35μm CMOS process,and it achieved 92.8 dB SNDR and 101 dB DR with a signal bandwidth of 100 kHz dissipating 8.6 mW power from a 3.3-V supply.The performance satisfies the requirements of a GSM system.展开更多
A fourth-order switched-capacitor bandpass ∑△ modulator is presented for digital intermediatefrequency （IF） receivers. The circuit operates at a sampling frequency of 100 MHz. The transfer function of the resonato...A fourth-order switched-capacitor bandpass ∑△ modulator is presented for digital intermediatefrequency （IF） receivers. The circuit operates at a sampling frequency of 100 MHz. The transfer function of the resonator considering nonidealities of the operational amplifier is proposed so as to optimize the performance of resonators. The modulator is implemented in a 0.13-μm standard CMOS process. The measurement shows that the signal-to-noise-and-distortion ratio and dynamic range achieve 68 dB and 75 dB, respectively, over a bandwidth of 200 kHz centered at 25 MHz, and the power dissipation is 8.2 mW at a 1.2 V supply.展开更多
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the National Natural Science Foundation of China (No. 60025101, No.90207001, and No. 90307016).
文摘This paper investigates the design of digital Sigma-Delta Modulator (SDM) for fractional-N frequency synthesizer. Characteristics of SDMs are compared through theory analysis and simulation. The curve of maximum-loop-bandwidth vs. maximum-phase-noise is suggested to be a new criterion to the performance of SDM,which greatly helps designers to select an appropriate SDM structure to meet their real application requirements and to reduce the cost as low as possible. A low-spur 3-order Mul-tistage Noise Shaping (MASH)-1-1-1 SDM using three 2-bit first-order cascaded modulators is proposed,which balances the requirements of tone-free and maximum operation frequency.
文摘This paper presents the design and experimental results of a continuous-time (CT) sigma-delta (ΣΔ) modulator with data-weighted average (DWA) technology for WiMAX applications. The proposed modulator comprises a third-order active RC loop filter, internal quantizer operating at 160 MHz and three DAC circuits. A multi-bit quantizer is used to increase resolution and multi-bit non-return-to-zero (NRZ) DACs are adopted to reduce clock jitter sensitivity. The NRZ DAC circuits with quantizer excess loop delay compensation are set to be half the sampling period of the quantizer for increasing modulator stability. A dynamic element matching (DEM) technique is applied to multi-bit ΣΔ modulators to improve the nonlinearity of the internal DAC. This approach translates the harmonic distortion components of a nonideal DAC in the feedback loop of a ΣΔ modulator to high-frequency components. Capacitor tuning is utilized to overcome loop coefficient shifts due to process variations. The DWA technique is used for reducing DAC noise due to component mismatches. The prototype is implemented in TSMC 0.18 um CMOS process. Experimental results show that the ΣΔ modulator achieves 54-dB dynamic range, 51-dB SNR, and 48-dB SNDR over a 10-MHz signal bandwidth with an oversampling ratio (OSR) of 8, while dissipating 19.8 mW from a 1.2-V supply. Including pads, the chip area is 1.156 mm2.
基金Sponsored by the National Basic Research Program of China(Grant No.2012CB934104)
文摘In this paper,in order to reduce power consumption and chip area,as well as to improve the performance of the bandpass sigma-delta modulator,a novel full differential feedforward fourth-order bandpass sigma-delta modulator was proposed. It used a resonator based on Salo architecture,which employed doublesampling and double-delay technique. The results show that the proposed modulator can achieve lower power consumption and a lower capacitive load than the conventional bandpass modulators on the platform of Simulink. The circuit is implemented with TSMC0. 18 μm CMOS process and operates at a sampling frequency of 20 MHz, 80 MHz effective sampling frequency. Furthermore,it consumes 21. 2 mW from a 1. 8 V supply. The simulated peak signal-to-noise ratio( SNR) is 85. 9 dB and the dynamic range( DR) is 91 dB with 200 kHz bandwidth.
基金Sponsored by the Top Scientific and Technological Innovation Team from Beijing University of Chemical Technology(Grant No.BUCTYLKJCX06)
文摘It is usually difficult to design a high performance Sigma⁃Delta(ΣΔ)modulator due to system noises.In this paper,a disturbance observer(DOB)is utilized to estimate the system noises and eliminate their effects on ΣΔ modulators.The applied DOB is introduced with a Bode's ideal cut⁃off(BICO)filter used for the Q⁃filter.The proposed DOB with the BICO filter used in ΣΔ modulators can achieve better noise⁃shaping ability,resulting from the less phase loss of the BICO filter.Finally,the simulation results show that the proposed BICO filter scheme is a useful additional tool for improving the performance of ΣΔ modulators.
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].
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.
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 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).
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.
文摘This paper introduces a high-revolution,200kHz signal bandwidth EA modulator for low-IF GSM receivers that adopts a 2-1 cascaded single-bit structure to achieve high linearity and stability. Our design is realized in a standard 0.18μm CMOS process with art active area of 0.5mm× 1.1mm.The EA modulator is driven by a single 19.2MHz clock signal and dissipates 5.88mW from 3V power supply. The experimental results show that,with an oversampling ratio of 48, the modulator achieves a 84.4dB dynamic range,73.8dB peak SNDR, and 80dB peak SNR in the signal bandwidth of 200kHz.
基金the National Natural Science Foundation of China(No.90707002)~~
文摘To improve the simulation accuracy of SIMULINK, a novel inclusive behavior model of an integrator is proposed that introduces the effects of different circuit nonidealities of a switched-capacitor sigma-delta modulator into SIMULIK simulation. The nonlinear DC gain and nonlinear settling process are introduced into the op-amp module. The signaldependent charge injection and nonlinear resistance are introduced into the switch module. In addition, the noise source including flicker and thermal noise is introduced into system as an independent module. The novel model is verified by SIMULINK behavioral simulations. The results are compared with results from circuit level simulation in Cadence SPICE using TSMC 0.35μm mixed signal technology. It shows that the novel model succeeds in introducing the influences of the nonidealities into behavior simulation to more realistically describe the circuit performances and increase the accuracy of SIMULINK simulation.
基金Project supported by the National Science Fund for Distinguished Young Scholars of China(No.60925015)
文摘Traditional feedforward structures suffer from performance constraints caused by the complex adder before quantizer.This paper presents an improved 4th-order 1 -bit sigma-delta modulator which has a simple adder and delayed input feedforward to relax timing constraints and implement low-distortion.The modulator was fabricated in a 0.35μm CMOS process,and it achieved 92.8 dB SNDR and 101 dB DR with a signal bandwidth of 100 kHz dissipating 8.6 mW power from a 3.3-V supply.The performance satisfies the requirements of a GSM system.
基金Project supported by the National High Technology Research and Development Program of China(No.2009AA011600)the Young Scientists Fund of Fudan University,China(No.09FQ33)the State Key Laboratory ASIC & System of Fudan University,China(No. 09MS008)
文摘A fourth-order switched-capacitor bandpass ∑△ modulator is presented for digital intermediatefrequency （IF） receivers. The circuit operates at a sampling frequency of 100 MHz. The transfer function of the resonator considering nonidealities of the operational amplifier is proposed so as to optimize the performance of resonators. The modulator is implemented in a 0.13-μm standard CMOS process. The measurement shows that the signal-to-noise-and-distortion ratio and dynamic range achieve 68 dB and 75 dB, respectively, over a bandwidth of 200 kHz centered at 25 MHz, and the power dissipation is 8.2 mW at a 1.2 V supply.
