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
The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling pathways.Physical properties of the extracellular matrix such as s...The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling pathways.Physical properties of the extracellular matrix such as stiffness and topography affect such interactions.Our recent work reveals that surface topography of tens to hundreds of nanometer scale modulates cell signaling by activating intracellular curvature-sensitive proteins.We use vertical nanostructures protruding from a flat surface as a platform to induce precise curvatures on the cell membrane and to probe biological processes in live cells.Vertical nanopillars deform the plasma membrane inwards and induce membrane curvature when the cell engulfs them,leading to a reduction of the membrane-substrate gap distance.We found that the high membrane curvature induced by vertical nanopillars significantly affects the distribution of curvature-sensitive proteins and stimulates several cellular processes in live cells including cellular endocytosis and cytoskeleton dynamics.Our studies show a strong interplay between biological cells and nano-featured surfaces,which is an essential consideration for future development of interfacing devices.展开更多
Dopamine is a neurotransmitter crucial for movement, mood, drug addiction and many neural degeneration diseases including Parkinson’s disease. Micro electrochemical carbon
CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about it...CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about its function on T lymphocyte mediated immune response to alloantigen. Here we report that we successfully deleted CD98hc in T cells by crossing mice bearing a loxP-flanked Slc3a2 allele with those expressing Cre re-combinase in T cells（CD4-Cre+）.T cell-specific deficient of CD98hc resulted in lower responses to alloantigen stimulation in mixed lymphocyte reaction assay.Heterotopic cardiac grafting was then performed from BALB/c（H-2K<sup>d</sup>） to CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> /C57BL/6（H-2K<sup>b</sup>） or control littermate C57BL/6 （B6） mice.We found that all CD98hc<sup>lox/</sup>-CD4-Cre<sup>+</sup> recipients had indefinite survival（MST:】100days, n=8）.In contrast,all littermate B6 recipients suffered acute rejection[MST:（7.4±0.5）d,n=12].In addition,the survival of the skin grafts from donor BALB/c mice to more than postoperative day （POD） 100 heart-bearing tolerant CD98hc<sup>lox/-</sup>CD4- Cre<sup>+</sup> recipients was significantly prolonged[MST: （15.2±2.2）d,n =5]compared that of the B6 mice [MST:（8.2±1.3）d,n=9].In consistent with graft survival, we found that the graft infiltration cells on POD7 were fewer than that of the B6 mice by FACS and immune-staining analysis.Also chemotaxis assay data revealed that the migrated CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> lymphocyte were less than that of B6 in the presence of different concentration of chemokines CCL2, CCL5,and CCL2 plus CCL5.In addition,a neutralizing antibody（clone 26-24）specific against CD98hc prolonged the graft survival[MST:（13.4±2.7）d,n=8; P=0.001]in the B6 recipients after they received the BALB/c mice heart.Hence our data indicated that T cell-specific deficient of CD98hc impaired proliferate in response to alloantigens and decreased migration ability result in inducing immune tolerance after cardiac transplantation.Moreover,the application of the blocked of CD98hc by monoclonal antibody is effective in the treatment of acute cardiac allograft rejection, which may be useful clinically in the future.展开更多
In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral is...In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA. The increased ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine. The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to manage neuronal damage.展开更多
Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a co...Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the disease.In this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced ALF.Our results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage microenvironment.The cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for detoxification.More importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ALF.Furthermore,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival rate.In summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.展开更多
Background: We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study...Background: We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study, we investigated the kinetics of Treg induction as well as their long-term homing in spleen and lungs correlating with reduced airway hyperresponsiveness (AHR) in a murine model of acute allergic asthma. We then evaluated the therapeutic implication of EFD BCG in a chronic asthma model. Methods: Tregs expressing Foxp3 were analyzed in various organs shortly and long-term after EFD BCG, live- and Heat Killed-(HK-) BCG treatments in an acute model of asthma. We further studied EFD BCG treatment on airway inflammation using a chronic model of asthma in mice. Results: Foxp3 expression peaked in the inguinal draining lymph-nodes (iDLNs) 2-4 days after EFD BCG treatment whereas it was long-term observed in spleen (days 7 to 90). This increase in Foxp3 expression was also found in lungs upon intranasal ovalbumin (OVA) challenge in OVA-sensitized mice. The loss of protection 4 months after EFD BCG treatment was correlated with the end of this phenomenon. Moreover, major lung inflammation hallmarks of severe asthma after multiple allergen challenges promoting chronic airway inflammation in OVA sensitized mice were reduced by EFD BCG treatment: AHR, eosinophils and neutrophils in bronchoalveolar lavage (BAL), mucus metaplasia, Th2 as well as Th17 cytokine levels in BAL and sera. EFD BCG treatment also enhances PPAR-γ expression and regulates NF-κBp65 translocation in lung extracts in this model of chronic asthma. Conclusions: EFD BCG treatment induced long-term protective effect associated to Foxp3 Tregs in the spleen and lungs in an acute model of asthma and inhibits AHR in a chronic model of asthma. EFD BCG could be a new and promising immuno-modulatory alternative treatment to corticoids in severe human asthma.展开更多
Photovoltaic (PV) modules, as essential components of solar power generation systems, significantly influence unitpower generation costs.The service life of these modules directly affects these costs. Over time, the p...Photovoltaic (PV) modules, as essential components of solar power generation systems, significantly influence unitpower generation costs.The service life of these modules directly affects these costs. Over time, the performanceof PV modules gradually declines due to internal degradation and external environmental factors.This cumulativedegradation impacts the overall reliability of photovoltaic power generation. This study addresses the complexdegradation process of PV modules by developing a two-stage Wiener process model. This approach accountsfor the distinct phases of degradation resulting from module aging and environmental influences. A powerdegradation model based on the two-stage Wiener process is constructed to describe individual differences inmodule degradation processes. To estimate the model parameters, a combination of the Expectation-Maximization(EM) algorithm and the Bayesian method is employed. Furthermore, the Schwarz Information Criterion (SIC) isutilized to identify critical change points in PV module degradation trajectories. To validate the universality andeffectiveness of the proposed method, a comparative analysis is conducted against other established life predictiontechniques for PV modules.展开更多
The plant cell wall is an important interface for sensing pathogen attack and activating signaling pathways that promote plant immune responses.THESEUS1(THE1) acts as a sensor of cell wall integrity that controls cell...The plant cell wall is an important interface for sensing pathogen attack and activating signaling pathways that promote plant immune responses.THESEUS1(THE1) acts as a sensor of cell wall integrity that controls cell elongation during plant growth.However, no specific role for THE1 in plant defense responses has been reported. Here, we found that THE1 interacts with GUANINE EXCHANGE FACTOR4(GEF4)and that both proteins play regulatory roles in plant resistance to the necrotrophic fungus Botrytis cinerea.Genetic analysis showed that THE1 and GEF4 function in the same genetic pathway to mediate plant defense responses. In addition, using transcriptome analysis, we identified various genes(such as defense-related,secondary metabolite-related, and transcription factor genes) that are likely downstream targets in the THE1-GEF4 signaling pathway. Our results suggest that THE1 functions as an upstream regulator of GEF4 signaling to positively regulate defense responses against B. cinerea in Arabidopsis.展开更多
Lightweight high/medium-entropy alloys(H/MEAs)possess attractive properties such as high strength-to-weight ratios,however,their limited room-temperature tensile ductility hinders their widespread engi-neering impleme...Lightweight high/medium-entropy alloys(H/MEAs)possess attractive properties such as high strength-to-weight ratios,however,their limited room-temperature tensile ductility hinders their widespread engi-neering implementation,for instance in aerospace structural components.This work achieved a transfor-mative improvement of room-temperature tensile ductility in Ti-V-Zr-Nb MEAs with densities of 5.4-6.5 g/cm3,via ingenious composition modulation.Through the systematic co-adjustment of Ti and V contents,an intrinsic ductility mechanism was unveiled,manifested by a transition from predominant intergranular brittle fracture to pervasive ductile dimpled rupture.Notably,the modulated deformation mechanisms evolved from solitary slip toward collaborative multiple slip modes,without significantly compromising strength.Compared to equimolar Ti-V-Zr-Nb,a(Ti1.5V)3ZrNb composition demonstrated an impressive 360%improvement in elongation while sustaining a high yield strength of around 800 MPa.Increasing Ti and V not only purified the grain boundaries by reducing detrimental phases,but also tai-lored the deformation dislocation configurations.These insights expanded the applicability of lightweight HEAs to areas demanding combined high strength and ductility.展开更多
Diatomic metasurfaces designed for interferometric mechanisms possess significant potential for the multidimensional manipulation of electromagnetic waves,including control over amplitude,phase,frequency,and polarizat...Diatomic metasurfaces designed for interferometric mechanisms possess significant potential for the multidimensional manipulation of electromagnetic waves,including control over amplitude,phase,frequency,and polarization.Geometric phase profiles with spin-selective properties are commonly associated with wavefront modulation,allowing the implementation of conjugate strategies within orthogonal circularly polarized channels.Simultaneous control of these characteristics in a single-layered diatomic metasurface will be an apparent technological extension.Here,spin-selective modulation of terahertz(THz)beams is realized by assembling a pair of meta-atoms with birefringent effects.The distinct modulation functions arise from geometric phase profiles characterized by multiple rotational properties,which introduce independent parametric factors that elucidate their physical significance.By arranging the key parameters,the proposed design strategy can be employed to realize independent amplitude and phase manipulation.A series of THz metasurface samples with specific modulation functions are characterized,experimentally demonstrating the accuracy of on-demand manipulation.This research paves the way for all-silicon meta-optics that may have great potential in imaging,sensing and detection.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
A two-way K/Ka-band series-Doherty PA(SDPA)with a distributed impedance inverting network(IIN)for millimeter wave applications is presented in this article.The proposed distributed IIN contributes to achieve wideband ...A two-way K/Ka-band series-Doherty PA(SDPA)with a distributed impedance inverting network(IIN)for millimeter wave applications is presented in this article.The proposed distributed IIN contributes to achieve wideband linear and power back-off(PBO)efficiency enhancement.Implemented in 65 nm bulk CMOS technology,this work realizes a measured 3 dB band-width of 15.5 GHz with 21.2 dB peak small-signal gain at 34.2 GHz.Under 1-V power supply,it achieves OP1dB over 13.4 dBm and Psat over 16 dBm between 21 to 30 GHz.The measured maximum Psat,OP1dB,peak/OP1dB/6dBPBO PAE results are 17.5,14.7 dBm,and 28.2%/23.2%/13.2%.Without digital pre-distortion(DPD)and equalization,EVMs are lower than-25.2 dB for 200 MHz 64-QAM signals.Besides,this work achieves-33.35,-23.52,and-20 dB EVMs for 100 MHz 256-QAM,600 MHz 64-QAM and 2 GHz 16-QAM signals at 27 GHz without DPD and equalization.展开更多
All-season thermal management with zero energy consumption and emissions is more crucial to global decarbonization over traditional energy-intensive cooling/heating systems.However,the static single thermal management...All-season thermal management with zero energy consumption and emissions is more crucial to global decarbonization over traditional energy-intensive cooling/heating systems.However,the static single thermal management for cooling or heating fails to self-regulate the temperature in dynamic seasonal temperature condition.Herein,inspired by the dual-temperature regulation function of the fur color changes on the backs and abdomens of penguins,a smart thermal management composite hydrogel(PNA@H-PM Gel)system was subtly created though an"on-demand"dual-layer structure design strategy.The PNA@H-PM Gel system features synchronous solar and thermal radiation modulation as well as tunable phase transition temperatures to meet the variable seasonal thermal requirements and energy-saving demands via self-adaptive radiative cooling and solar heating regulation.Furthermore,this system demonstrates superb modulations of both the solar reflectance(ΔR=0.74)and thermal emissivity(ΔE=0.52)in response to ambient temperature changes,highlighting efficient temperature regulation with average radiative cooling and solar heating effects of 9.6℃in summer and 6.1℃in winter,respectively.Moreover,compared to standard building baselines,the PNA@H-PM Gel presents a more substantial energy-saving cooling/heating potentials for energy-efficient buildings across various regions and climates.This novel solution,inspired by penguins in the real world,will offer a fresh approach for producing intelligent,energy-saving thermal management materials,and serve for temperature regulation under dynamic climate conditions and even throughout all seasons.展开更多
The traditional von Neumann architecture faces inherent limitations due to the separation of memory and computa-tion,leading to high energy consumption,significant latency,and reduced operational efficiency.Neuromorph...The traditional von Neumann architecture faces inherent limitations due to the separation of memory and computa-tion,leading to high energy consumption,significant latency,and reduced operational efficiency.Neuromorphic computing,inspired by the architecture of the human brain,offers a promising alternative by integrating memory and computational func-tions,enabling parallel,high-speed,and energy-efficient information processing.Among various neuromorphic technologies,ion-modulated optoelectronic devices have garnered attention due to their excellent ionic tunability and the availability of multi-dimensional control strategies.This review provides a comprehensive overview of recent progress in ion-modulation optoelec-tronic neuromorphic devices.It elucidates the key mechanisms underlying ionic modulation of light fields,including ion migra-tion dynamics and capture and release of charge through ions.Furthermore,the synthesis of active materials and the proper-ties of these devices are analyzed in detail.The review also highlights the application of ion-modulation optoelectronic devices in artificial vision systems,neuromorphic computing,and other bionic fields.Finally,the existing challenges and future direc-tions for the development of optoelectronic neuromorphic devices are discussed,providing critical insights for advancing this promising field.展开更多
The four-level nested neutral-point-clamped(4L-NNPC)inverter is a competitive topology among the various medium-voltage multilevel converters,and its main issue is flying-capacitor voltage unbalance.In this article,a ...The four-level nested neutral-point-clamped(4L-NNPC)inverter is a competitive topology among the various medium-voltage multilevel converters,and its main issue is flying-capacitor voltage unbalance.In this article,a novel carrier-interleaved pulse width modulation(CIPWM)method that satisfies the volt-sec balance principle is proposed with an advanced carrier distribution rule.By adopting the proposed CIPWM method,the redundant switching states of 4L-NNPC inverters can be evenly distributed into the output PWM waveform in each carrier period,and natural flying-capacitor voltage balance can be achieved.Furthermore,an active balancing strategy is also proposed to eliminate the voltage unbalance caused by nonideal factors,which is realized by simply adjusting the duty cycle and with no need to adjust the redundant switching states for 4L-NNPC inverters.The simulation and experimental results verify the effectiveness of the proposed CIPWM method and the flying-capacitor voltage balancing strategy.展开更多
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supported by two NIH grants 1R01GM125737 and 1R01GM117263 to BC
文摘The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling pathways.Physical properties of the extracellular matrix such as stiffness and topography affect such interactions.Our recent work reveals that surface topography of tens to hundreds of nanometer scale modulates cell signaling by activating intracellular curvature-sensitive proteins.We use vertical nanostructures protruding from a flat surface as a platform to induce precise curvatures on the cell membrane and to probe biological processes in live cells.Vertical nanopillars deform the plasma membrane inwards and induce membrane curvature when the cell engulfs them,leading to a reduction of the membrane-substrate gap distance.We found that the high membrane curvature induced by vertical nanopillars significantly affects the distribution of curvature-sensitive proteins and stimulates several cellular processes in live cells including cellular endocytosis and cytoskeleton dynamics.Our studies show a strong interplay between biological cells and nano-featured surfaces,which is an essential consideration for future development of interfacing devices.
基金Supported by grant from Chinese NSFC "973" program
文摘Dopamine is a neurotransmitter crucial for movement, mood, drug addiction and many neural degeneration diseases including Parkinson’s disease. Micro electrochemical carbon
文摘CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about its function on T lymphocyte mediated immune response to alloantigen. Here we report that we successfully deleted CD98hc in T cells by crossing mice bearing a loxP-flanked Slc3a2 allele with those expressing Cre re-combinase in T cells（CD4-Cre+）.T cell-specific deficient of CD98hc resulted in lower responses to alloantigen stimulation in mixed lymphocyte reaction assay.Heterotopic cardiac grafting was then performed from BALB/c（H-2K<sup>d</sup>） to CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> /C57BL/6（H-2K<sup>b</sup>） or control littermate C57BL/6 （B6） mice.We found that all CD98hc<sup>lox/</sup>-CD4-Cre<sup>+</sup> recipients had indefinite survival（MST:】100days, n=8）.In contrast,all littermate B6 recipients suffered acute rejection[MST:（7.4±0.5）d,n=12].In addition,the survival of the skin grafts from donor BALB/c mice to more than postoperative day （POD） 100 heart-bearing tolerant CD98hc<sup>lox/-</sup>CD4- Cre<sup>+</sup> recipients was significantly prolonged[MST: （15.2±2.2）d,n =5]compared that of the B6 mice [MST:（8.2±1.3）d,n=9].In consistent with graft survival, we found that the graft infiltration cells on POD7 were fewer than that of the B6 mice by FACS and immune-staining analysis.Also chemotaxis assay data revealed that the migrated CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> lymphocyte were less than that of B6 in the presence of different concentration of chemokines CCL2, CCL5,and CCL2 plus CCL5.In addition,a neutralizing antibody（clone 26-24）specific against CD98hc prolonged the graft survival[MST:（13.4±2.7）d,n=8; P=0.001]in the B6 recipients after they received the BALB/c mice heart.Hence our data indicated that T cell-specific deficient of CD98hc impaired proliferate in response to alloantigens and decreased migration ability result in inducing immune tolerance after cardiac transplantation.Moreover,the application of the blocked of CD98hc by monoclonal antibody is effective in the treatment of acute cardiac allograft rejection, which may be useful clinically in the future.
文摘In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA. The increased ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine. The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to manage neuronal damage.
基金supported by National Natural Science Foundation of China(Project No.81872805,82073771,82104085)Guangdong Basic and Applied Basic Research Foundation(Project No.2020A1515110147,2021A1515011418,2021A1515012025)。
文摘Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the disease.In this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced ALF.Our results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage microenvironment.The cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for detoxification.More importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ALF.Furthermore,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival rate.In summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.
文摘Background: We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study, we investigated the kinetics of Treg induction as well as their long-term homing in spleen and lungs correlating with reduced airway hyperresponsiveness (AHR) in a murine model of acute allergic asthma. We then evaluated the therapeutic implication of EFD BCG in a chronic asthma model. Methods: Tregs expressing Foxp3 were analyzed in various organs shortly and long-term after EFD BCG, live- and Heat Killed-(HK-) BCG treatments in an acute model of asthma. We further studied EFD BCG treatment on airway inflammation using a chronic model of asthma in mice. Results: Foxp3 expression peaked in the inguinal draining lymph-nodes (iDLNs) 2-4 days after EFD BCG treatment whereas it was long-term observed in spleen (days 7 to 90). This increase in Foxp3 expression was also found in lungs upon intranasal ovalbumin (OVA) challenge in OVA-sensitized mice. The loss of protection 4 months after EFD BCG treatment was correlated with the end of this phenomenon. Moreover, major lung inflammation hallmarks of severe asthma after multiple allergen challenges promoting chronic airway inflammation in OVA sensitized mice were reduced by EFD BCG treatment: AHR, eosinophils and neutrophils in bronchoalveolar lavage (BAL), mucus metaplasia, Th2 as well as Th17 cytokine levels in BAL and sera. EFD BCG treatment also enhances PPAR-γ expression and regulates NF-κBp65 translocation in lung extracts in this model of chronic asthma. Conclusions: EFD BCG treatment induced long-term protective effect associated to Foxp3 Tregs in the spleen and lungs in an acute model of asthma and inhibits AHR in a chronic model of asthma. EFD BCG could be a new and promising immuno-modulatory alternative treatment to corticoids in severe human asthma.
基金supported by the National Natural Science Foundation of China(51767017)the Basic Research Innovation Group Project of Gansu Province(18JR3RA133)the Industrial Support and Guidance Project of Universities in Gansu Province(2022CYZC-22).
文摘Photovoltaic (PV) modules, as essential components of solar power generation systems, significantly influence unitpower generation costs.The service life of these modules directly affects these costs. Over time, the performanceof PV modules gradually declines due to internal degradation and external environmental factors.This cumulativedegradation impacts the overall reliability of photovoltaic power generation. This study addresses the complexdegradation process of PV modules by developing a two-stage Wiener process model. This approach accountsfor the distinct phases of degradation resulting from module aging and environmental influences. A powerdegradation model based on the two-stage Wiener process is constructed to describe individual differences inmodule degradation processes. To estimate the model parameters, a combination of the Expectation-Maximization(EM) algorithm and the Bayesian method is employed. Furthermore, the Schwarz Information Criterion (SIC) isutilized to identify critical change points in PV module degradation trajectories. To validate the universality andeffectiveness of the proposed method, a comparative analysis is conducted against other established life predictiontechniques for PV modules.
基金supported by the National Natural Science Foundation of China(31400221)the Beijing Advanced Innovation Center for Tree Breeding by Molecular Design+1 种基金the Program for Changjiang Scholars and Innovative Research Team in University(IRT13047)the Fundamental Research Funds for the Central Universities(BLX2012038)
文摘The plant cell wall is an important interface for sensing pathogen attack and activating signaling pathways that promote plant immune responses.THESEUS1(THE1) acts as a sensor of cell wall integrity that controls cell elongation during plant growth.However, no specific role for THE1 in plant defense responses has been reported. Here, we found that THE1 interacts with GUANINE EXCHANGE FACTOR4(GEF4)and that both proteins play regulatory roles in plant resistance to the necrotrophic fungus Botrytis cinerea.Genetic analysis showed that THE1 and GEF4 function in the same genetic pathway to mediate plant defense responses. In addition, using transcriptome analysis, we identified various genes(such as defense-related,secondary metabolite-related, and transcription factor genes) that are likely downstream targets in the THE1-GEF4 signaling pathway. Our results suggest that THE1 functions as an upstream regulator of GEF4 signaling to positively regulate defense responses against B. cinerea in Arabidopsis.
基金supported by the National Natural Science Foundation of China(Nos.51925103,52271149,52171159)the Innovation Program of Shanghai Municipal Education Commission(No.2021-01-07-00-09-E00114)+5 种基金the Natural Science Foundation of Shanghai(22ZR1422500)the Innovation Program of Shanghai Science and Technology(No.23520760700)the Aviation Foundation(No.2023Z0530S6004)the Fund of the State Key Laboratory of Solidification Processing in NWPU(No.SKLSP202221)the financial support from Program 173(No.2020-JCIQ-ZD-186-01)the Space Utilization System of China Manned Space Engineering(No.KJZ-YY-NCL08).
文摘Lightweight high/medium-entropy alloys(H/MEAs)possess attractive properties such as high strength-to-weight ratios,however,their limited room-temperature tensile ductility hinders their widespread engi-neering implementation,for instance in aerospace structural components.This work achieved a transfor-mative improvement of room-temperature tensile ductility in Ti-V-Zr-Nb MEAs with densities of 5.4-6.5 g/cm3,via ingenious composition modulation.Through the systematic co-adjustment of Ti and V contents,an intrinsic ductility mechanism was unveiled,manifested by a transition from predominant intergranular brittle fracture to pervasive ductile dimpled rupture.Notably,the modulated deformation mechanisms evolved from solitary slip toward collaborative multiple slip modes,without significantly compromising strength.Compared to equimolar Ti-V-Zr-Nb,a(Ti1.5V)3ZrNb composition demonstrated an impressive 360%improvement in elongation while sustaining a high yield strength of around 800 MPa.Increasing Ti and V not only purified the grain boundaries by reducing detrimental phases,but also tai-lored the deformation dislocation configurations.These insights expanded the applicability of lightweight HEAs to areas demanding combined high strength and ductility.
基金supports from National Key Research and Development Program of China(2021YFB2800703)Sichuan Province Science and Technology Support Program(25QNJJ2419)+1 种基金National Natural Science Foundation of China(U22A2008,12404484)Laoshan Laboratory Science and Technology Innovation Project(LSKJ202200801).
文摘Diatomic metasurfaces designed for interferometric mechanisms possess significant potential for the multidimensional manipulation of electromagnetic waves,including control over amplitude,phase,frequency,and polarization.Geometric phase profiles with spin-selective properties are commonly associated with wavefront modulation,allowing the implementation of conjugate strategies within orthogonal circularly polarized channels.Simultaneous control of these characteristics in a single-layered diatomic metasurface will be an apparent technological extension.Here,spin-selective modulation of terahertz(THz)beams is realized by assembling a pair of meta-atoms with birefringent effects.The distinct modulation functions arise from geometric phase profiles characterized by multiple rotational properties,which introduce independent parametric factors that elucidate their physical significance.By arranging the key parameters,the proposed design strategy can be employed to realize independent amplitude and phase manipulation.A series of THz metasurface samples with specific modulation functions are characterized,experimentally demonstrating the accuracy of on-demand manipulation.This research paves the way for all-silicon meta-optics that may have great potential in imaging,sensing and detection.
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.
基金supported in part by the National Key Research and Development Program of China under Grant 2020YFB1807300the Beijing Advanced Innovation Center for Integrated Circuits。
文摘A two-way K/Ka-band series-Doherty PA(SDPA)with a distributed impedance inverting network(IIN)for millimeter wave applications is presented in this article.The proposed distributed IIN contributes to achieve wideband linear and power back-off(PBO)efficiency enhancement.Implemented in 65 nm bulk CMOS technology,this work realizes a measured 3 dB band-width of 15.5 GHz with 21.2 dB peak small-signal gain at 34.2 GHz.Under 1-V power supply,it achieves OP1dB over 13.4 dBm and Psat over 16 dBm between 21 to 30 GHz.The measured maximum Psat,OP1dB,peak/OP1dB/6dBPBO PAE results are 17.5,14.7 dBm,and 28.2%/23.2%/13.2%.Without digital pre-distortion(DPD)and equalization,EVMs are lower than-25.2 dB for 200 MHz 64-QAM signals.Besides,this work achieves-33.35,-23.52,and-20 dB EVMs for 100 MHz 256-QAM,600 MHz 64-QAM and 2 GHz 16-QAM signals at 27 GHz without DPD and equalization.
基金the funding and generous support of the National Natural Science Foundation of China(52103263,52271249)the Key Project of International Science&Technology Cooperation of Shaanxi Province(2023-GHZD-09)+5 种基金the Key Project of Science Foundation of Education Department of Shaanxi Province(22JY011)the Key Project of Scientific Research and Development of Shaanxi Province(2023GXLH-070)the Qinchuangyuan"Scientist+Engineer"Team of Shaanxi Province(2023KXJ-069)the Key Research and Development Program of Shaanxi(2023-YBGY-488)the Sci-tech Innovation Team of Shaanxi Province(2024RS-CXTD-46)the Key Research and Development Program of Shaanxi Province(2020ZDLGY13-11).
文摘All-season thermal management with zero energy consumption and emissions is more crucial to global decarbonization over traditional energy-intensive cooling/heating systems.However,the static single thermal management for cooling or heating fails to self-regulate the temperature in dynamic seasonal temperature condition.Herein,inspired by the dual-temperature regulation function of the fur color changes on the backs and abdomens of penguins,a smart thermal management composite hydrogel(PNA@H-PM Gel)system was subtly created though an"on-demand"dual-layer structure design strategy.The PNA@H-PM Gel system features synchronous solar and thermal radiation modulation as well as tunable phase transition temperatures to meet the variable seasonal thermal requirements and energy-saving demands via self-adaptive radiative cooling and solar heating regulation.Furthermore,this system demonstrates superb modulations of both the solar reflectance(ΔR=0.74)and thermal emissivity(ΔE=0.52)in response to ambient temperature changes,highlighting efficient temperature regulation with average radiative cooling and solar heating effects of 9.6℃in summer and 6.1℃in winter,respectively.Moreover,compared to standard building baselines,the PNA@H-PM Gel presents a more substantial energy-saving cooling/heating potentials for energy-efficient buildings across various regions and climates.This novel solution,inspired by penguins in the real world,will offer a fresh approach for producing intelligent,energy-saving thermal management materials,and serve for temperature regulation under dynamic climate conditions and even throughout all seasons.
基金supported by National Natural Science Foundation of China(62174164,U23A20568,and U22A2075)National Key Research and Development Project(2021YFA1202600)+2 种基金Talent Plan of Shanghai Branch,Chinese Academy of Sciences(CASSHB-QNPD-2023-022)Ningbo Technology Project(2022A-007-C)Ningbo Key Research and Development Project(2023Z021).
文摘The traditional von Neumann architecture faces inherent limitations due to the separation of memory and computa-tion,leading to high energy consumption,significant latency,and reduced operational efficiency.Neuromorphic computing,inspired by the architecture of the human brain,offers a promising alternative by integrating memory and computational func-tions,enabling parallel,high-speed,and energy-efficient information processing.Among various neuromorphic technologies,ion-modulated optoelectronic devices have garnered attention due to their excellent ionic tunability and the availability of multi-dimensional control strategies.This review provides a comprehensive overview of recent progress in ion-modulation optoelec-tronic neuromorphic devices.It elucidates the key mechanisms underlying ionic modulation of light fields,including ion migra-tion dynamics and capture and release of charge through ions.Furthermore,the synthesis of active materials and the proper-ties of these devices are analyzed in detail.The review also highlights the application of ion-modulation optoelectronic devices in artificial vision systems,neuromorphic computing,and other bionic fields.Finally,the existing challenges and future direc-tions for the development of optoelectronic neuromorphic devices are discussed,providing critical insights for advancing this promising field.
基金supported by Beijing Natural Science Foundation under Grant L242006.
文摘The four-level nested neutral-point-clamped(4L-NNPC)inverter is a competitive topology among the various medium-voltage multilevel converters,and its main issue is flying-capacitor voltage unbalance.In this article,a novel carrier-interleaved pulse width modulation(CIPWM)method that satisfies the volt-sec balance principle is proposed with an advanced carrier distribution rule.By adopting the proposed CIPWM method,the redundant switching states of 4L-NNPC inverters can be evenly distributed into the output PWM waveform in each carrier period,and natural flying-capacitor voltage balance can be achieved.Furthermore,an active balancing strategy is also proposed to eliminate the voltage unbalance caused by nonideal factors,which is realized by simply adjusting the duty cycle and with no need to adjust the redundant switching states for 4L-NNPC inverters.The simulation and experimental results verify the effectiveness of the proposed CIPWM method and the flying-capacitor voltage balancing strategy.
