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 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
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
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
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
Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic su...Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic surgeries.The unpredictable nature of this condition,combined with limited treatment options,poses a significant burden on patients,their families,and society.Spinal cord ischemia-reperfusion injury leads to reduced neuronal regenerative capacity and complex pathological processes.In contrast,mitophagy is crucial for degrading damaged mitochondria,thereby supporting neuronal metabolism and energy supply.However,while moderate mitophagy can be beneficial in the context of spinal cord ischemia-reperfusion injury,excessive mitophagy may be detrimental.Therefore,this review aims to investigate the potential mechanisms and regulators of mitophagy involved in the pathological processes of spinal cord ischemia-reperfusion injury.The goal is to provide a comprehensive understanding of recent advancements in mitophagy related to spinal cord ischemia-reperfusion injury and clarify its potential clinical applications.展开更多
Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
RAV1(Related to ABI3/VP1)is a plant-specific B3 and AP2 domain-containing transcription factor that acts as a negative regulator of growth in many plant species.The expression of RAV1 is downregulated by brassinostero...RAV1(Related to ABI3/VP1)is a plant-specific B3 and AP2 domain-containing transcription factor that acts as a negative regulator of growth in many plant species.The expression of RAV1 is downregulated by brassinosteroids(BRs);large-scale transcriptome analyses have shown that the expression of RAV1 was previously targeted by BRI1-EMS-SUPPRESOR1(BES1)and BRASSINAZOLE-RESISTANT1(BZR1),which are critical transcription factors for the BR-signaling process.Using RAV1-overexpressing transgenic plants,we showed that RAV1 overexpression reduced the BR signaling capacity,resulting in the downregulation of BR biosynthetic genes and BES1 expression.Furthermore,we demonstrated that BES1,not BZR1,is directly bound to the RAV1 promoter and repressed RAV1 expression,and vice versa;RAV1 is also bound to the BES1 promoter and repressed BES1 expression.This mutual inhibition was specific to RAV1 and BES1 because RAV1 exhibited binding activity to the BZR1 promoter but did not repress BZR1 expression.We observed that constitutively activated BR signaling phenotypes in bes1-D were attenuated by the repression of endogenous BES1 expression in transgenic bes1-D plants overexpressing RAV1.RNA-sequencing analysis of RAV1-overexpressing transgenic plants and bes1-D mutant plants revealed differentially expressed genes by RAV1 and BES1 and genes that were oppositely co-regulated by RAV1 and BES1.RAV1 and BES1 regulated different transcriptomes but co-regulated a specific set of genes responsible for the balance between growth and defense.These results suggested that the mutual inhibitory transcriptional activities of RAV1 and BES1 provide fine regulatory mechanisms for plant growth and development.展开更多
Objective To observe the regulatory mechanism ofβ-catenin in modulating the expression of E-cadherin in TGF-β1 induced epithelial-mesenchymal transition (EMT). Methods The substrate mimetic peptide and control pepti...Objective To observe the regulatory mechanism ofβ-catenin in modulating the expression of E-cadherin in TGF-β1 induced epithelial-mesenchymal transition (EMT). Methods The substrate mimetic peptide and control peptide were constructed. The human tubular cells (HK2 cell line) were cultured with 10 ng/ml TGF-β1 for 72 hours, in the group of the substrate-analogue peptide and control peptide the cells were incubated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
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 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 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 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.
基金supported by Cuiying Scientific and Technological Innovation Program of Second Hospital of Lanzhou University,Nos.CY2023-QN-B18(to YD),2020QN-16(to YZ)the Natural Science Foundation of Gansu Province,No.22JR11RA082(to YZ)Key R&D Plan of Gansu Provincial Department of Science and Technology-Social Development Projects,No.23YFFA0043(to XK).
文摘Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic surgeries.The unpredictable nature of this condition,combined with limited treatment options,poses a significant burden on patients,their families,and society.Spinal cord ischemia-reperfusion injury leads to reduced neuronal regenerative capacity and complex pathological processes.In contrast,mitophagy is crucial for degrading damaged mitochondria,thereby supporting neuronal metabolism and energy supply.However,while moderate mitophagy can be beneficial in the context of spinal cord ischemia-reperfusion injury,excessive mitophagy may be detrimental.Therefore,this review aims to investigate the potential mechanisms and regulators of mitophagy involved in the pathological processes of spinal cord ischemia-reperfusion injury.The goal is to provide a comprehensive understanding of recent advancements in mitophagy related to spinal cord ischemia-reperfusion injury and clarify its potential clinical applications.
基金supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
基金supported by grants from the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT,and Future Planning(NRF-2017R1A2B4002656 and 2020R1F1A1067946 to K.H.N.and 2021R1A6A3A13045111 to D.Y.)。
文摘RAV1(Related to ABI3/VP1)is a plant-specific B3 and AP2 domain-containing transcription factor that acts as a negative regulator of growth in many plant species.The expression of RAV1 is downregulated by brassinosteroids(BRs);large-scale transcriptome analyses have shown that the expression of RAV1 was previously targeted by BRI1-EMS-SUPPRESOR1(BES1)and BRASSINAZOLE-RESISTANT1(BZR1),which are critical transcription factors for the BR-signaling process.Using RAV1-overexpressing transgenic plants,we showed that RAV1 overexpression reduced the BR signaling capacity,resulting in the downregulation of BR biosynthetic genes and BES1 expression.Furthermore,we demonstrated that BES1,not BZR1,is directly bound to the RAV1 promoter and repressed RAV1 expression,and vice versa;RAV1 is also bound to the BES1 promoter and repressed BES1 expression.This mutual inhibition was specific to RAV1 and BES1 because RAV1 exhibited binding activity to the BZR1 promoter but did not repress BZR1 expression.We observed that constitutively activated BR signaling phenotypes in bes1-D were attenuated by the repression of endogenous BES1 expression in transgenic bes1-D plants overexpressing RAV1.RNA-sequencing analysis of RAV1-overexpressing transgenic plants and bes1-D mutant plants revealed differentially expressed genes by RAV1 and BES1 and genes that were oppositely co-regulated by RAV1 and BES1.RAV1 and BES1 regulated different transcriptomes but co-regulated a specific set of genes responsible for the balance between growth and defense.These results suggested that the mutual inhibitory transcriptional activities of RAV1 and BES1 provide fine regulatory mechanisms for plant growth and development.
文摘Objective To observe the regulatory mechanism ofβ-catenin in modulating the expression of E-cadherin in TGF-β1 induced epithelial-mesenchymal transition (EMT). Methods The substrate mimetic peptide and control peptide were constructed. The human tubular cells (HK2 cell line) were cultured with 10 ng/ml TGF-β1 for 72 hours, in the group of the substrate-analogue peptide and control peptide the cells were incubated
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.
