The caries-preventive effects of arginine have been attributed to its impact on biofilm composition and pH.Recent in vitro studies suggest that arginine also affects the production of biofilm matrix components that co...The caries-preventive effects of arginine have been attributed to its impact on biofilm composition and pH.Recent in vitro studies suggest that arginine also affects the production of biofilm matrix components that contribute to virulence,but this mechanism has not been investigated clinically.This randomized,placebo-controlled,triple-blind,split-mouth in situ trial assessed arginine's impact on the microbial composition,matrix architecture,and microscale pH of biofilms from caries-active patients(N=10).We also examined whether individual differences in the pH response to arginine were related to biofilm composition and matrix structure.Biofilms were grown for four days on carriers attached to intraoral splints.Three times daily,the biofilms were treated extraorally with sucrose(5 min),followed by arginine or placebo(30 min),in a split-mouth design.After growth,the microscale biofilm p H response to sucrose was monitored by pH ratiometry.Microbial biofilm composition and carbohydrate matrix architecture were analyzed by 16S rRNA gene sequencing and fluorescence lectin-binding analysis,respectively.Arginine treatment significantly mitigated sucrose-induced pH drops,reduced total carbohydrate matrix production,and altered the spatial distribution of fucoseand galactose-containing carbohydrates.Both arginine-and placebo-treated biofilms were dominated by streptococci and Veillonella spp.Paired analyses showed a significant reduction in mitis/oralis group streptococci and a non-significant increase in several arginine metabolizers in arginine-treated biofilms.Individual pH responses were not significantly associated with the abundance of specific bacterial taxa or carbohydrate matrix components.In conclusion,arginine reduced the virulence of biofilms from caries-active patients through multiple mechanisms,including suppressing matrix carbohydrate production.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
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
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
In this paper,we introduce the notion of G_(C)-X-injective modules,where X denotes a class of left S-modules and C represents a faithfully semidualizing bimodule.Under the condition that X satisfies certain hypotheses...In this paper,we introduce the notion of G_(C)-X-injective modules,where X denotes a class of left S-modules and C represents a faithfully semidualizing bimodule.Under the condition that X satisfies certain hypotheses,some properties and some equivalent characterizations of G_(C)-X-injective modules are investigated,and we also show that the triple(■,cores■,■)is a weak co-AB-context.As an application,two complete cotorsion pairs and a new model structure in Mod S are given.展开更多
[Background]High harmonic cavities are widely used in electron storage rings to lengthen thebunch,lower the bunch peak current,thereby reducing the IBS effect,enhancing the Touschek lifetime,as well asproviding Landau...[Background]High harmonic cavities are widely used in electron storage rings to lengthen thebunch,lower the bunch peak current,thereby reducing the IBS effect,enhancing the Touschek lifetime,as well asproviding Landau damping,which is particularly important for storage rings operating with ultra-low emittance or atlow beam energy.[Purpose]To further increase the bunch length without additional hardware costs,the phasemodulation in a dual-RF system is considered.[Methods]In this paper,turn-by-turn simulations incorporating randomsynchrotron radiation excitation are conducted,and a brief analysis is presented to explain the bunch lengtheningmechanism.[Results]Simulation results reveal that the peak current can be further reduced,thereby mitigating IBSeffects and enhancing the Touschek lifetime.Although the energy spread increases,which tends to reduce thebrightness of higher-harmonic radiation from the undulator,the brightness of the fundamental harmonic can,in fact,beimproved.展开更多
The suppression of ablative Rayleigh–Taylor instability(ARTI)by a spatially modulated laser in inertial confinement fusion(ICF)is studied through numerical simulations.The results show that in the acceleration phase ...The suppression of ablative Rayleigh–Taylor instability(ARTI)by a spatially modulated laser in inertial confinement fusion(ICF)is studied through numerical simulations.The results show that in the acceleration phase of ICF implosion,the growth of ARTI can be suppressed by using a short-wavelength spatially modulated laser.The ARTI growth rate decreases as the wavelength of the spatially modulated laser decreases,and ARTI is completely suppressed after a certain wavelength has been reached.A spatially uniform laser is introduced to keep the state of motion of the implosion fluid consistent,and it is found that the proportion of the spatially modulated laser required for complete suppression of ARTI decreases as the wavelength continues to decrease.We also optimize the spatial intensity distribution of the spatially modulated laser.In addition,as the duration of the spatially modulated laser decreases,the proportion required for completely suppressing ARTI increases,but the required energy decreases.When the perturbation wavenumber decreases,the wavelength of the spatially modulated laser required for complete suppression of ARTI becomes longer.In the case of multimode perturbation,ARTI can also be significantly suppressed by a spatially modulated laser,and the perturbation amplitude can be reduced to less than 10% of that without a spatially modulated laser.We believe that the conclusions drawn from our simulations can provide the basis for new approaches to control ARTI in ICF.展开更多
The escalating global issues of water scarcity and pollution emphasize the critical need for the rapid development of efficient and eco-friendly water treatment technologies.Photoelectrocatalytic technology has emerge...The escalating global issues of water scarcity and pollution emphasize the critical need for the rapid development of efficient and eco-friendly water treatment technologies.Photoelectrocatalytic technology has emerged as a promising solution for effectively degrading refractory organic pollutants in water under light conditions.This review delves into the advancements made in the field,focusing on strategies to enhance the generation of active species by modulating the micro-interface of the photoanode.Strategies,such as morphological control,element doping,introduction of surface oxygen vacancies,and construction of heterostructures,significantly improve the separation efficiency of photogenerated charges and the generation of active species,thereby boosting the efficiency of photoelectrocatalytic performance.Furthermore,the review explores the potential applications of photoelectrocatalytic technology in organic pollutant degradation in solutions.It also outlines the current challenges and future development directions.Despite its remarkable laboratory success,practical implementation of photoelectrocatalytic technology encounters obstacles related to stability,cost-effectiveness,and operational efficiency.Future investigations need to focus on optimizing the performance of photoelectrocatalytic materials and exploring strategies for upscaling their application in real water treatment scenarios.展开更多
While reinforcement learning-based underwater acoustic adaptive modulation shows promise for enabling environment-adaptive communication as supported by extensive simulation-based research,its practical performance re...While reinforcement learning-based underwater acoustic adaptive modulation shows promise for enabling environment-adaptive communication as supported by extensive simulation-based research,its practical performance remains underexplored in field investigations.To evaluate the practical applicability of this emerging technique in adverse shallow sea channels,a field experiment was conducted using three communication modes:orthogonal frequency division multiplexing(OFDM),M-ary frequency-shift keying(MFSK),and direct sequence spread spectrum(DSSS)for reinforcement learning-driven adaptive modulation.Specifically,a Q-learning method is used to select the optimal modulation mode according to the channel quality quantified by signal-to-noise ratio,multipath spread length,and Doppler frequency offset.Experimental results demonstrate that the reinforcement learning-based adaptive modulation scheme outperformed fixed threshold detection in terms of total throughput and average bit error rate,surpassing conventional adaptive modulation strategies.展开更多
Zinc telluride(ZnTe)with high density and low cost is considered as promising anode for sodium-ion batteries.However,ZnTe suffers from continuous capacity degradation owing to the low electronic conductivity,large vol...Zinc telluride(ZnTe)with high density and low cost is considered as promising anode for sodium-ion batteries.However,ZnTe suffers from continuous capacity degradation owing to the low electronic conductivity,large volume expansion,and high ion-diffusion energy barriers.Herein,the nitrogen-doped carbon confined ZnTe polyhedron heterostructure(ZnTe/NC)is proposed,exploiting its orbital rehybridization and the realignment of energy level to improve storage performance.Systematic ex situ/in situ characterizations and simulations demonstrated that the elaborate ZnTe/NC offers abundant electron/ion transport pathways,accelerates Na^(+)diffusion kinetics,and alleviates huge volume expansion.Notably,the nitrogen-doped carbon-support interaction induced via electron transfer between ZnTe sites and support elevates the energy level of Zn 3d orbital,greatly enhancing ion adsorption capability and reducing the ion diffusion barrier.As a result,the ZnTe/NC anode delivers a high discharge capacity of 470.5 mAh g^(−1)and long cycling durability over 1000 cycles.This work uncovers that optimizing sodium ion adsorption and diffusion via d-orbital energy level modulation enabled by nitrogen-doped support interaction is an effective method for developing high-performance transition metal telluride anodes for alkali ion storage.展开更多
Accurate and rapid recognition of weathering degree(WD)and groundwater condition(GC)is essential for evaluating rock mass quality and conducting stability analyses in underground engineering.Conventional WD and GC rec...Accurate and rapid recognition of weathering degree(WD)and groundwater condition(GC)is essential for evaluating rock mass quality and conducting stability analyses in underground engineering.Conventional WD and GC recognition methods often rely on subjective evaluation by field experts,supplemented by field sampling and laboratory testing.These methods are frequently complex and timeconsuming,making it challenging to meet the rapidly evolving demands of underground engineering.Therefore,this study proposes a rock non-geometric parameter classification network(RNPC-net)to rapidly achieve the recognition and mapping ofWD and GC of tunnel faces.The hybrid feature extraction module(HFEM)in RNPC-net can fully extract,fuse,and utilize multi-scale features of images,enhancing the network's classification performance.Moreover,the designed adaptive weighting auxiliary classifier(AC)helps the network learn features more efficiently.Experimental results show that RNPC-net achieved classification accuracies of 0.8756 and 0.8710 for WD and GC,respectively,representing an improvement of approximately 2%e10%compared to other methods.Both quantitative and qualitative experiments confirm the effectiveness and superiority of RNPC-net.Furthermore,for WD and GC mapping,RNPC-net outperformed other methods by achieving the highest mean intersection over union(mIOU)across most tunnel faces.The mapping results closely align with measurements provided by field experts.The application of WD and GC mapping results to the rock mass rating(RMR)system achieved a transition from conventional qualitative to quantitative evaluation.This advancement enables more accurate and reliable rock mass quality evaluations,particularly under critical conditions of RMR.展开更多
In sediment transport on a mobile erodible bed,near-bed particles tend to preferentially locate under specific flow regions and form an uneven bedform.These moving and mobile particles can significantly modulate turbu...In sediment transport on a mobile erodible bed,near-bed particles tend to preferentially locate under specific flow regions and form an uneven bedform.These moving and mobile particles can significantly modulate turbulence at various scales,from inertial large-scale motions to small viscous motions.This study analyzes the particle-resolved direct numerical simulation data of particle-laden two-phase flow with multilayers of particles in turbulent flows over static and mobile beds.The double-average method is adopted for energy transfer analysis.The result shows that the alternative streaky bedform in the spanwise directions correlates with the streak structures in the near-wall turbulence in the mobile bed case.The energy redistribution and exchange,as well as the dissipation,are analyzed in detail,and an energy transfer diagram is given in the last to summarize the energy transfer processes.In both the static and mobile bed cases,flow energy is introduced into the system via the work performed by volume forces acting on the mean flow.The viscous dissipations in the double mean and form-induced fields are more pronounced in the static bed case,and the work done by the fluid-particle interfacial stress in the double mean and turbulent fields is more pronounced in the mobile bed case.The prominent energy contribution in the form-induced field is the production by the form-induced stress on the mean strain in the mobile bed case.In addition,sediment transport involving a limited number of mobile particles is insufficient to capture the energy transfer processes that occur over the troughs and may intertwine the energy transfer processes over the mobile particles and the fixed particle bed.展开更多
The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they ...The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.展开更多
基金supported by the Faculty of Health,Aarhus University,Denmark。
文摘The caries-preventive effects of arginine have been attributed to its impact on biofilm composition and pH.Recent in vitro studies suggest that arginine also affects the production of biofilm matrix components that contribute to virulence,but this mechanism has not been investigated clinically.This randomized,placebo-controlled,triple-blind,split-mouth in situ trial assessed arginine's impact on the microbial composition,matrix architecture,and microscale pH of biofilms from caries-active patients(N=10).We also examined whether individual differences in the pH response to arginine were related to biofilm composition and matrix structure.Biofilms were grown for four days on carriers attached to intraoral splints.Three times daily,the biofilms were treated extraorally with sucrose(5 min),followed by arginine or placebo(30 min),in a split-mouth design.After growth,the microscale biofilm p H response to sucrose was monitored by pH ratiometry.Microbial biofilm composition and carbohydrate matrix architecture were analyzed by 16S rRNA gene sequencing and fluorescence lectin-binding analysis,respectively.Arginine treatment significantly mitigated sucrose-induced pH drops,reduced total carbohydrate matrix production,and altered the spatial distribution of fucoseand galactose-containing carbohydrates.Both arginine-and placebo-treated biofilms were dominated by streptococci and Veillonella spp.Paired analyses showed a significant reduction in mitis/oralis group streptococci and a non-significant increase in several arginine metabolizers in arginine-treated biofilms.Individual pH responses were not significantly associated with the abundance of specific bacterial taxa or carbohydrate matrix components.In conclusion,arginine reduced the virulence of biofilms from caries-active patients through multiple mechanisms,including suppressing matrix carbohydrate production.
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(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.
文摘In this paper,we introduce the notion of G_(C)-X-injective modules,where X denotes a class of left S-modules and C represents a faithfully semidualizing bimodule.Under the condition that X satisfies certain hypotheses,some properties and some equivalent characterizations of G_(C)-X-injective modules are investigated,and we also show that the triple(■,cores■,■)is a weak co-AB-context.As an application,two complete cotorsion pairs and a new model structure in Mod S are given.
基金National Natural Science Foundation of China(12405168)The Fundamental Research Funds for the Central Universities,China(2024CDJXY004)。
文摘[Background]High harmonic cavities are widely used in electron storage rings to lengthen thebunch,lower the bunch peak current,thereby reducing the IBS effect,enhancing the Touschek lifetime,as well asproviding Landau damping,which is particularly important for storage rings operating with ultra-low emittance or atlow beam energy.[Purpose]To further increase the bunch length without additional hardware costs,the phasemodulation in a dual-RF system is considered.[Methods]In this paper,turn-by-turn simulations incorporating randomsynchrotron radiation excitation are conducted,and a brief analysis is presented to explain the bunch lengtheningmechanism.[Results]Simulation results reveal that the peak current can be further reduced,thereby mitigating IBSeffects and enhancing the Touschek lifetime.Although the energy spread increases,which tends to reduce thebrightness of higher-harmonic radiation from the undulator,the brightness of the fundamental harmonic can,in fact,beimproved.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.12074399,12204500,and 12004403)the Key Projects of Intergovernmental International Scientific and Technological Innovation Cooperation(No.2021YFE0116700)+1 种基金the Shanghai Natural Science Foundation(No.20ZR1464400)the Shanghai Sailing Program(No.22YF1455300).
文摘The suppression of ablative Rayleigh–Taylor instability(ARTI)by a spatially modulated laser in inertial confinement fusion(ICF)is studied through numerical simulations.The results show that in the acceleration phase of ICF implosion,the growth of ARTI can be suppressed by using a short-wavelength spatially modulated laser.The ARTI growth rate decreases as the wavelength of the spatially modulated laser decreases,and ARTI is completely suppressed after a certain wavelength has been reached.A spatially uniform laser is introduced to keep the state of motion of the implosion fluid consistent,and it is found that the proportion of the spatially modulated laser required for complete suppression of ARTI decreases as the wavelength continues to decrease.We also optimize the spatial intensity distribution of the spatially modulated laser.In addition,as the duration of the spatially modulated laser decreases,the proportion required for completely suppressing ARTI increases,but the required energy decreases.When the perturbation wavenumber decreases,the wavelength of the spatially modulated laser required for complete suppression of ARTI becomes longer.In the case of multimode perturbation,ARTI can also be significantly suppressed by a spatially modulated laser,and the perturbation amplitude can be reduced to less than 10% of that without a spatially modulated laser.We believe that the conclusions drawn from our simulations can provide the basis for new approaches to control ARTI in ICF.
基金financially supported by the National Natural Science Foundation of China (No.52100076)the Fundamental Research Funds for the Central Universities (No.2023MS064)。
文摘The escalating global issues of water scarcity and pollution emphasize the critical need for the rapid development of efficient and eco-friendly water treatment technologies.Photoelectrocatalytic technology has emerged as a promising solution for effectively degrading refractory organic pollutants in water under light conditions.This review delves into the advancements made in the field,focusing on strategies to enhance the generation of active species by modulating the micro-interface of the photoanode.Strategies,such as morphological control,element doping,introduction of surface oxygen vacancies,and construction of heterostructures,significantly improve the separation efficiency of photogenerated charges and the generation of active species,thereby boosting the efficiency of photoelectrocatalytic performance.Furthermore,the review explores the potential applications of photoelectrocatalytic technology in organic pollutant degradation in solutions.It also outlines the current challenges and future development directions.Despite its remarkable laboratory success,practical implementation of photoelectrocatalytic technology encounters obstacles related to stability,cost-effectiveness,and operational efficiency.Future investigations need to focus on optimizing the performance of photoelectrocatalytic materials and exploring strategies for upscaling their application in real water treatment scenarios.
基金funding from the National Key Research and Development Program of China(No.2018YFE0110000)the National Natural Science Foundation of China(No.11274259,No.11574258)the Science and Technology Commission Foundation of Shanghai(21DZ1205500)in support of the present research.
文摘While reinforcement learning-based underwater acoustic adaptive modulation shows promise for enabling environment-adaptive communication as supported by extensive simulation-based research,its practical performance remains underexplored in field investigations.To evaluate the practical applicability of this emerging technique in adverse shallow sea channels,a field experiment was conducted using three communication modes:orthogonal frequency division multiplexing(OFDM),M-ary frequency-shift keying(MFSK),and direct sequence spread spectrum(DSSS)for reinforcement learning-driven adaptive modulation.Specifically,a Q-learning method is used to select the optimal modulation mode according to the channel quality quantified by signal-to-noise ratio,multipath spread length,and Doppler frequency offset.Experimental results demonstrate that the reinforcement learning-based adaptive modulation scheme outperformed fixed threshold detection in terms of total throughput and average bit error rate,surpassing conventional adaptive modulation strategies.
基金supported by the National Natural Science Foundation of China(52402298,52172224,52302240)Science and Technology Correspondent Project of Tianjin(24YDTPJC00240)+1 种基金the Macao Young Scholars Program(AM2023011)the Yuanguang Scholars Program,Hebei University of Technology(282022554).
文摘Zinc telluride(ZnTe)with high density and low cost is considered as promising anode for sodium-ion batteries.However,ZnTe suffers from continuous capacity degradation owing to the low electronic conductivity,large volume expansion,and high ion-diffusion energy barriers.Herein,the nitrogen-doped carbon confined ZnTe polyhedron heterostructure(ZnTe/NC)is proposed,exploiting its orbital rehybridization and the realignment of energy level to improve storage performance.Systematic ex situ/in situ characterizations and simulations demonstrated that the elaborate ZnTe/NC offers abundant electron/ion transport pathways,accelerates Na^(+)diffusion kinetics,and alleviates huge volume expansion.Notably,the nitrogen-doped carbon-support interaction induced via electron transfer between ZnTe sites and support elevates the energy level of Zn 3d orbital,greatly enhancing ion adsorption capability and reducing the ion diffusion barrier.As a result,the ZnTe/NC anode delivers a high discharge capacity of 470.5 mAh g^(−1)and long cycling durability over 1000 cycles.This work uncovers that optimizing sodium ion adsorption and diffusion via d-orbital energy level modulation enabled by nitrogen-doped support interaction is an effective method for developing high-performance transition metal telluride anodes for alkali ion storage.
基金supported by the National Natural Science Foundation of China(Grant Nos.42077242 and 42171407)the Graduate Innovation Fund of Jilin University.
文摘Accurate and rapid recognition of weathering degree(WD)and groundwater condition(GC)is essential for evaluating rock mass quality and conducting stability analyses in underground engineering.Conventional WD and GC recognition methods often rely on subjective evaluation by field experts,supplemented by field sampling and laboratory testing.These methods are frequently complex and timeconsuming,making it challenging to meet the rapidly evolving demands of underground engineering.Therefore,this study proposes a rock non-geometric parameter classification network(RNPC-net)to rapidly achieve the recognition and mapping ofWD and GC of tunnel faces.The hybrid feature extraction module(HFEM)in RNPC-net can fully extract,fuse,and utilize multi-scale features of images,enhancing the network's classification performance.Moreover,the designed adaptive weighting auxiliary classifier(AC)helps the network learn features more efficiently.Experimental results show that RNPC-net achieved classification accuracies of 0.8756 and 0.8710 for WD and GC,respectively,representing an improvement of approximately 2%e10%compared to other methods.Both quantitative and qualitative experiments confirm the effectiveness and superiority of RNPC-net.Furthermore,for WD and GC mapping,RNPC-net outperformed other methods by achieving the highest mean intersection over union(mIOU)across most tunnel faces.The mapping results closely align with measurements provided by field experts.The application of WD and GC mapping results to the rock mass rating(RMR)system achieved a transition from conventional qualitative to quantitative evaluation.This advancement enables more accurate and reliable rock mass quality evaluations,particularly under critical conditions of RMR.
基金supported by the National Natural Science Foundation of China(Grant Nos.12388101 and 12472221)the Fundamental Research Funds for the Central Universities(Grant No.lzujbky-2024-oy10).
文摘In sediment transport on a mobile erodible bed,near-bed particles tend to preferentially locate under specific flow regions and form an uneven bedform.These moving and mobile particles can significantly modulate turbulence at various scales,from inertial large-scale motions to small viscous motions.This study analyzes the particle-resolved direct numerical simulation data of particle-laden two-phase flow with multilayers of particles in turbulent flows over static and mobile beds.The double-average method is adopted for energy transfer analysis.The result shows that the alternative streaky bedform in the spanwise directions correlates with the streak structures in the near-wall turbulence in the mobile bed case.The energy redistribution and exchange,as well as the dissipation,are analyzed in detail,and an energy transfer diagram is given in the last to summarize the energy transfer processes.In both the static and mobile bed cases,flow energy is introduced into the system via the work performed by volume forces acting on the mean flow.The viscous dissipations in the double mean and form-induced fields are more pronounced in the static bed case,and the work done by the fluid-particle interfacial stress in the double mean and turbulent fields is more pronounced in the mobile bed case.The prominent energy contribution in the form-induced field is the production by the form-induced stress on the mean strain in the mobile bed case.In addition,sediment transport involving a limited number of mobile particles is insufficient to capture the energy transfer processes that occur over the troughs and may intertwine the energy transfer processes over the mobile particles and the fixed particle bed.
基金supported in part by the Rosetrees Trust(#CF-2023-I-2_113)by the Israel Ministry of Innovation,Science,and Technology(#7393)(to ES).
文摘The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.
