To create a green and healthy living environment,people have put forward higher requirements for the refined management of ecological resources.A variety of technologies,including satellite remote sensing,Internet of ...To create a green and healthy living environment,people have put forward higher requirements for the refined management of ecological resources.A variety of technologies,including satellite remote sensing,Internet of Things,artificial intelligence,and big data,can build a smart environmental monitoring system.Remote sensing image classification is an important research content in ecological environmental monitoring.Remote sensing images contain rich spatial information andmulti-temporal information,but also bring challenges such as difficulty in obtaining classification labels and low classification accuracy.To solve this problem,this study develops a transductive transfer dictionary learning(TTDL)algorithm.In the TTDL,the source and target domains are transformed fromthe original sample space to a common subspace.TTDL trains a shared discriminative dictionary in this subspace,establishes associations between domains,and also obtains sparse representations of source and target domain data.To obtain an effective shared discriminative dictionary,triple-induced ordinal locality preserving term,Fisher discriminant term,and graph Laplacian regularization termare introduced into the TTDL.The triplet-induced ordinal locality preserving term on sub-space projection preserves the local structure of data in low-dimensional subspaces.The Fisher discriminant term on dictionary improves differences among different sub-dictionaries through intra-class and inter-class scatters.The graph Laplacian regularization term on sparse representation maintains the manifold structure using a semi-supervised weight graphmatrix,which can indirectly improve the discriminative performance of the dictionary.The TTDL is tested on several remote sensing image datasets and has strong discrimination classification performance.展开更多
Network forensics is a security infrastructure,and becomes the research focus of forensic investigation.However many challenges still exist in conducting network forensics:network has produced large amounts of data;th...Network forensics is a security infrastructure,and becomes the research focus of forensic investigation.However many challenges still exist in conducting network forensics:network has produced large amounts of data;the comprehensibility of evidence extracting from collected data;the efficiency of evidence analysis methods,etc.To solve these problems,in this paper we develop a network intrusion forensics system based on transductive scheme that can detect and analyze efficiently computer crime in networked environments,and extract digital evidence automatically.At the end of the paper,we evaluate our method on a series of experiments on KDD Cup 1999 dataset.The results demonstrate that our methods are actually effective for real-time network forensics,and can provide comprehensible aid for a forensic expert.展开更多
In many machine learning problems, a large amount of data is available but only a few of them can be labeled easily. This provides a research branch to effectively combine unlabeled and labeled data to infer the label...In many machine learning problems, a large amount of data is available but only a few of them can be labeled easily. This provides a research branch to effectively combine unlabeled and labeled data to infer the labels of unlabeled ones, that is, to develop transductive learning. In this article, based on Pattern classification via single sphere （SSPC）, which seeks a hypersphere to separate data with the maximum separation ratio, a progressive transductive pattern classification method via single sphere （PTSSPC） is proposed to construct the classifier using both the labeled and unlabeled data. PTSSPC utilize the additional information of the unlabeled samples and obtain better classification performance than SSPC when insufficient labeled data information is available. Experiment results show the algorithm can yields better performance.展开更多
Researchers face many class prediction challenges stemming from a small size of training data vis-a-vis a large number of unlabeled samples to be predicted. Transductive learning is proposed to utilize information abo...Researchers face many class prediction challenges stemming from a small size of training data vis-a-vis a large number of unlabeled samples to be predicted. Transductive learning is proposed to utilize information about unlabeled data to estimate labels of the unlabeled data for this condition. This work presents a new transductive learning method called two-way Markov random walk(TMRW) algorithm. The algorithm uses information about labeled and unlabeled data to predict the labels of the unlabeled data by taking random walks between the labeled and unlabeled data where data points are viewed as nodes of a graph. The labeled points correlate to unlabeled points and vice versa according to a transition probability matrix. We can get the predicted labels of unlabeled samples by combining the results of the two-way walks. Finally, ensemble learning is combined with transductive learning, and Adboost.MH is taken as the study framework to improve the performance of TMRW, which is the basic learner. Experiments show that this algorithm can predict labels of unlabeled data well.展开更多
Transductive support vector machine optimization problem is a NP problem, in the case of larger number of labeled samples, it is often difficult to obtain a global optimal solution, thereby the good generalization abi...Transductive support vector machine optimization problem is a NP problem, in the case of larger number of labeled samples, it is often difficult to obtain a global optimal solution, thereby the good generalization ability of transductive learning has been affected. Previous methods can not give consideration to both running efficiency and classification precision. In this paper, a transductive support vector machine algorithm based on ant colony optimization is proposed to overcome the drawbacks of the previous methods. The proposed algorithm approaches the approximate optimal solution of Transductive support vector machine optimization problem by ant colony optimization algorithm, and the advantage of transductive learning can be fully demonstrated. Experiments on several UCI standard datasets and the newsgroups 20 dataset showed that, with respect to running time and classification precision, the proposed algorithm has obvious advantage over the previous algorithms.展开更多
Survival analysis aims to predict the occurrence time of a particular event of interest,which is crucial for the prognosis analysis of diseases.Currently,due to the limited study period and potential losing tracks,the...Survival analysis aims to predict the occurrence time of a particular event of interest,which is crucial for the prognosis analysis of diseases.Currently,due to the limited study period and potential losing tracks,the observed data inevitably involve some censored instances,and thus brings a unique challenge that distinguishes from the general regression problems.In addition,survival analysis also suffers from other inherent challenges such as the high-dimension and small-sample-size problems.To address these challenges,we propose a novel multi-task regression learning model,i.e.,prior information guided transductive matrix completion(PigTMC)model,to predict the survival status of the new instances.Specifically,we use the multi-label transductive matrix completion framework to leverage the censored instances together with the uncensored instances as the training samples,and simultaneously employ the multi-task transductive feature selection scheme to alleviate the overfitting issue caused by high-dimension and small-sample-size data.In addition,we employ the prior temporal stability of the survival statuses at adjacent time intervals to guide survival analysis.Furthermore,we design an optimization algorithm with guaranteed convergence to solve the proposed PigTMC model.Finally,the extensive experiments performed on the real microarray gene expression datasets demonstrate that our proposed model outperforms the previously widely used competing methods.展开更多
After billions of years of evolution,biological intelligence has converged on unrivalled energy efficiency and environmental adaptability.The human brain,for instance,is highly efficient in information transmission,co...After billions of years of evolution,biological intelligence has converged on unrivalled energy efficiency and environmental adaptability.The human brain,for instance,is highly efficient in information transmission,consuming only about 20 W onaverage in a resting state[1,2].A key to this efficiency is that biological signal transduction and processing rely significantly on multi-ions as the signal carriers.Inspired by this paradigm.展开更多
Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling ...Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.展开更多
As sessile organisms,plants must adapt various stresses.Accordingly,they have evolved several plant-specific growth and developmental processes.WRKY53 is a member of the WRKY transcription factor family,which plays a ...As sessile organisms,plants must adapt various stresses.Accordingly,they have evolved several plant-specific growth and developmental processes.WRKY53 is a member of the WRKY transcription factor family,which plays a crucial role in rice growth and development,stress response,and hormone signal transduction.This review discusses the role of WRKY53 in stress response,focusing on its functions in cold tolerance,salt tolerance,disease resistance,and pest defense,and explores its role in regulating rice leaf senescence and seed germination.This article also proposes future research directions,including functional genomics studies,protein interaction network analyses,hormone signal transduction pathways,genetic improvement strategies,applications of gene editing technologies,molecular basis of stress responses,cross-species functional conservation,and bioinformatics and comparative genomics research.This review highlights the importance of WRKY53 in rice biology and provides new perspectives and strategies for future research and genetic improvement of rice.展开更多
Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to...Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to joint function loss and disability.Signal transducer and activator of transcription 3(STAT3)up-regulates the expression of MMP-13,which degrades collagen Ⅱ.Our previous study found that 5,7,3',4'-tetramethoxyflavone(TMF)exhibited protective effects on OA chondrocytes.This study aims to investigate the protective role of TMF in inhibiting ECM degradation by mediating the Sirt1/STAT3 signaling pathway.Methods:Rat OA models were established by the injection of monosodium iodoacetate(MIA).Hematoxylin&eosin(HE)staining and immunohistochemistry(IHC)analysis were performed.IL-1β stimulated C28/I2 cells were used as OA-like chondrocyte cell model.Western blotting assays were used to determine the protein expression.Results:The expression of MMP-13 was upregulated while type Ⅱ collagen expression is downregulated,and the phosphorylation level of STAT3 is increased in rat OA models.TMF reverses the STAT3-mediated expression of MMP-13 and type v collagen.Activation of STAT3 or inhibition of Sirt1 function attenuates the inhibitory effect of TMF on ECM degradation.Conclusion:TMF can inhibit ECM degradation mediated by the STAT3 signal pathway by activating Sirt1 expression in OA cell and animal models.展开更多
Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile ...Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular le...Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular level,many small molecules play crucial roles in balancing growth and defense,and stable high yields can be achieved by fine-tuning the responses to external stimuli.Therefore,it is essential to understand the molecular mechanisms underlying plant growth in response to heat stress and how plants can adjust their biological processes to survive heat stress conditions.In this review,we summarize the heat-responsive genetic networks in plants and crop plants based on recent studies.We focus on how plants sense the elevated temperatures and initiate the cellular and metabolic responses that allow them to adapt to the adverse growing conditions.We also describe the trade-off between plant growth and responses to heat stress.Specifically,we address the regulatory network of plant responses to heat stress,which will facilitate the discovery of novel thermotolerance genes and provide new opportunities for agricultural applications.展开更多
OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and ...OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.展开更多
The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally le...The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.展开更多
OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was establishe...OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.展开更多
OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
Ca^(2+)signaling plays crucial roles in plant stress responses,including defense against insects.To counteract insect feeding,different parts of a plant deploy systemic signaling to communicate and coordinate defense ...Ca^(2+)signaling plays crucial roles in plant stress responses,including defense against insects.To counteract insect feeding,different parts of a plant deploy systemic signaling to communicate and coordinate defense responses,but little is known about the underlying mechanisms.In this study,micrografting,in vivo imaging of Ca^(2+)and reactive oxygen species(ROS),quantification of jasmonic acid(JA)and defensive metabolites,and bioassay were used to study how Arabidopsis seedlings regulate systemic responses in leaves after hypocotyls are wounded.We show that wounding hypocotyls rapidly activated both Ca^(2+)and ROS signals in leaves.RBOHD,which functions to produce ROS,along with two glutamate receptors GLR3.3 and GLR3.6,but not individually RBOHD or GLR3.3 and GLR3.6,in hypocotyls regulate the dynamics of systemic Ca^(2+)signals in leaves.In line with the systemic Ca^(2+)signals,after wounding hypocotyl,RBOHD,GLR3.3,and GLR3.6 in hypocotyl also cooperatively regulate the transcriptome,hormone jasmonic acid,and defensive secondary metabolites in leaves of Arabidopsis seedlings,thus controlling the systemic resistance to insects.Unlike leaf-to-leaf systemic signaling,this study reveals the unique regulation of wounding-induced hypocotyl-to-leaf systemic signaling and sheds new light on how different plant organs use complex signaling pathways to modulate defense responses.展开更多
Upon encountering external challenges,immune cell recognition of response to pathogens constitutes a pivotal physiological process.Here,we designed and engineering an artificial immune signal transduction system utili...Upon encountering external challenges,immune cell recognition of response to pathogens constitutes a pivotal physiological process.Here,we designed and engineering an artificial immune signal transduction system utilizing DNA strands and liposomes to simulate antigen signals presentation,i.e.,the uptake and processing of antigens by antigen-presenting cells(APCs).Through controlled DNA strand displacement reactions,we engineered artificial antigen-presenting cells(mAPCs)that display antigen signals on their surface and mimic phagocytosis.To further simulate antigen presentation,we constructed mimic naïve T cells(mTCs).Then,deoxyribonucleic acid(DNA)ion channels across mTCs membranes,simulating Tcell receptors,were opened by DNA strands on mAPCs mimicking the major histocompatibility complex(MHC),i.e.,MHC molecules that present peptides to the T-cell receptor(TCR)on mTCs(recognition).This allowed Ca^(2+)ions to enter mTCs,increasing calcein fluorescence as activated mTC response indicator.The DNA strands on the surface of A-mAPCs and the Ca^(2+)ions in the solution together act like costimulatory molecules on APCs to trigger responses of mTCs.This simulation of immune signal transduction provides a significant reference value for the construction of bioinspired signal transduction systems and the design of more realistic artificial biological systems.展开更多
OBJECTIVES:To investigate the therapeutic effect of Huluan decotion(护卵汤,HLD)on cyclophosphamideinduced premature ovarian failure(POF)in mice and its regulatory mechanisms.METHODS:Female BALB/c mice were administere...OBJECTIVES:To investigate the therapeutic effect of Huluan decotion(护卵汤,HLD)on cyclophosphamideinduced premature ovarian failure(POF)in mice and its regulatory mechanisms.METHODS:Female BALB/c mice were administered cyclophosphamide and administered received different doses of HLD for 28 d.Levels of sex hormone,such as estradiol(E2),follicle stimulating hormone(FSH)and luteinizing hormone(LH)in the sera,were assessed using enzyme-linked immunosorbent assay(ELISA).Follicular structure variances were observed through hematoxylin and eosin(HE)staining,while Forkhead box L2(FOXL2)expression were analyzed via immuneohistochemical staining.The primary mechanism of POF were investigated through Western blot analysis.RESULTS:E2 levels decreased,and FSH and LH levels increased in POF model mice,but these trends were reversed with HLD or premarin administration,the expressions of WNT family member 4(Wnt4),β-Catenin and FOXL2 were downregulated in POF model mice,whereas high expression levels were observed in control mice and other groups.CONCLUSION:HLD effectively treats POF induced with cyclophosphamide in mice by enhancing expressions of Wnt4,β-Catenin and FOXL2.展开更多
基金This research was funded in part by the Natural Science Foundation of Jiangsu Province under Grant BK 20211333by the Science and Technology Project of Changzhou City(CE20215032).
文摘To create a green and healthy living environment,people have put forward higher requirements for the refined management of ecological resources.A variety of technologies,including satellite remote sensing,Internet of Things,artificial intelligence,and big data,can build a smart environmental monitoring system.Remote sensing image classification is an important research content in ecological environmental monitoring.Remote sensing images contain rich spatial information andmulti-temporal information,but also bring challenges such as difficulty in obtaining classification labels and low classification accuracy.To solve this problem,this study develops a transductive transfer dictionary learning(TTDL)algorithm.In the TTDL,the source and target domains are transformed fromthe original sample space to a common subspace.TTDL trains a shared discriminative dictionary in this subspace,establishes associations between domains,and also obtains sparse representations of source and target domain data.To obtain an effective shared discriminative dictionary,triple-induced ordinal locality preserving term,Fisher discriminant term,and graph Laplacian regularization termare introduced into the TTDL.The triplet-induced ordinal locality preserving term on sub-space projection preserves the local structure of data in low-dimensional subspaces.The Fisher discriminant term on dictionary improves differences among different sub-dictionaries through intra-class and inter-class scatters.The graph Laplacian regularization term on sparse representation maintains the manifold structure using a semi-supervised weight graphmatrix,which can indirectly improve the discriminative performance of the dictionary.The TTDL is tested on several remote sensing image datasets and has strong discrimination classification performance.
基金supported by the National Natural Science Foundation of China under Grant No.60903166 and 61170262the National High-Tech Research and Development Plan of China under Grant Nos.2012AA012506+4 种基金Specialized Research Fund for the Doctoral Program of Higher Education of China under Grant No.20121103120032the Humanity and Social Science Youth Foundation of Ministry of Education of China under Grant No.13YJCZH065General Program of Science and Technology Development Project of Beijing Municipal Education Commission of China under Grant No.km201410005012the Research on Education and Teaching of Beijing University of Technology under Grant No.ER2013C24Open Research Fund of Beijing Key Laboratory of Trusted Computing
文摘Network forensics is a security infrastructure,and becomes the research focus of forensic investigation.However many challenges still exist in conducting network forensics:network has produced large amounts of data;the comprehensibility of evidence extracting from collected data;the efficiency of evidence analysis methods,etc.To solve these problems,in this paper we develop a network intrusion forensics system based on transductive scheme that can detect and analyze efficiently computer crime in networked environments,and extract digital evidence automatically.At the end of the paper,we evaluate our method on a series of experiments on KDD Cup 1999 dataset.The results demonstrate that our methods are actually effective for real-time network forensics,and can provide comprehensible aid for a forensic expert.
基金supported by the National Natural Science of China(6057407560705004).
文摘In many machine learning problems, a large amount of data is available but only a few of them can be labeled easily. This provides a research branch to effectively combine unlabeled and labeled data to infer the labels of unlabeled ones, that is, to develop transductive learning. In this article, based on Pattern classification via single sphere （SSPC）, which seeks a hypersphere to separate data with the maximum separation ratio, a progressive transductive pattern classification method via single sphere （PTSSPC） is proposed to construct the classifier using both the labeled and unlabeled data. PTSSPC utilize the additional information of the unlabeled samples and obtain better classification performance than SSPC when insufficient labeled data information is available. Experiment results show the algorithm can yields better performance.
基金Project(61232001) supported by National Natural Science Foundation of ChinaProject supported by the Construct Program of the Key Discipline in Hunan Province,China
文摘Researchers face many class prediction challenges stemming from a small size of training data vis-a-vis a large number of unlabeled samples to be predicted. Transductive learning is proposed to utilize information about unlabeled data to estimate labels of the unlabeled data for this condition. This work presents a new transductive learning method called two-way Markov random walk(TMRW) algorithm. The algorithm uses information about labeled and unlabeled data to predict the labels of the unlabeled data by taking random walks between the labeled and unlabeled data where data points are viewed as nodes of a graph. The labeled points correlate to unlabeled points and vice versa according to a transition probability matrix. We can get the predicted labels of unlabeled samples by combining the results of the two-way walks. Finally, ensemble learning is combined with transductive learning, and Adboost.MH is taken as the study framework to improve the performance of TMRW, which is the basic learner. Experiments show that this algorithm can predict labels of unlabeled data well.
基金This work is sponsored by the National Natural Science Foundation of China (Nos. 61402246, 61402126, 61370083, 61370086, 61303193, and 61572268), a Project of Shandong Province Higher Educational Science and Technology Program (No. J15LN38,J14LN31), Qingdao indigenous innovation program (No. 15-9-1-47-jch), the Project of Shandong Provincial Natural Science Foundation of China (No. ZR2014FL019), the Open Project of Collaborative Innovation Center of Green Tyres & Rubber (No. 2014GTR0020), the National Research Foundation for the Doctoral Program of Higher Education of China (No.20122304110012), the Science and Technology Research Project Foundation of Heilongjiang Province Education Department (No. 12531105), Heilongjiang Province Postdoctoral Research Start Foundation (No. LBH-Q13092), and the National Key Technology R&D Program of the Ministry of Science and Technology under Grant No. 2012BAH81F02.
文摘Transductive support vector machine optimization problem is a NP problem, in the case of larger number of labeled samples, it is often difficult to obtain a global optimal solution, thereby the good generalization ability of transductive learning has been affected. Previous methods can not give consideration to both running efficiency and classification precision. In this paper, a transductive support vector machine algorithm based on ant colony optimization is proposed to overcome the drawbacks of the previous methods. The proposed algorithm approaches the approximate optimal solution of Transductive support vector machine optimization problem by ant colony optimization algorithm, and the advantage of transductive learning can be fully demonstrated. Experiments on several UCI standard datasets and the newsgroups 20 dataset showed that, with respect to running time and classification precision, the proposed algorithm has obvious advantage over the previous algorithms.
基金This work was supported in part by the National Natural Science Foundation of China(Grant Nos.61872190,61772285,61572263 and 61906098)in part by the Natural Science Foundation of Jiangsu Province(BK20161516)in part by the Open Fund of MIIT Key Laboratory of Pattern Analysis and Machine Intelligence of NUAA.
文摘Survival analysis aims to predict the occurrence time of a particular event of interest,which is crucial for the prognosis analysis of diseases.Currently,due to the limited study period and potential losing tracks,the observed data inevitably involve some censored instances,and thus brings a unique challenge that distinguishes from the general regression problems.In addition,survival analysis also suffers from other inherent challenges such as the high-dimension and small-sample-size problems.To address these challenges,we propose a novel multi-task regression learning model,i.e.,prior information guided transductive matrix completion(PigTMC)model,to predict the survival status of the new instances.Specifically,we use the multi-label transductive matrix completion framework to leverage the censored instances together with the uncensored instances as the training samples,and simultaneously employ the multi-task transductive feature selection scheme to alleviate the overfitting issue caused by high-dimension and small-sample-size data.In addition,we employ the prior temporal stability of the survival statuses at adjacent time intervals to guide survival analysis.Furthermore,we design an optimization algorithm with guaranteed convergence to solve the proposed PigTMC model.Finally,the extensive experiments performed on the real microarray gene expression datasets demonstrate that our proposed model outperforms the previously widely used competing methods.
文摘After billions of years of evolution,biological intelligence has converged on unrivalled energy efficiency and environmental adaptability.The human brain,for instance,is highly efficient in information transmission,consuming only about 20 W onaverage in a resting state[1,2].A key to this efficiency is that biological signal transduction and processing rely significantly on multi-ions as the signal carriers.Inspired by this paradigm.
基金supported by the National Natural Science Foundation of China,No.82101115(to JY)the Wuhan University Independent Innovation Fund Youth Project,No.2042021kf0094(to JY).
文摘Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.
基金supported by the Hubei Provincial Natural Science Foundation,China(Grant No.2024AFB917).
文摘As sessile organisms,plants must adapt various stresses.Accordingly,they have evolved several plant-specific growth and developmental processes.WRKY53 is a member of the WRKY transcription factor family,which plays a crucial role in rice growth and development,stress response,and hormone signal transduction.This review discusses the role of WRKY53 in stress response,focusing on its functions in cold tolerance,salt tolerance,disease resistance,and pest defense,and explores its role in regulating rice leaf senescence and seed germination.This article also proposes future research directions,including functional genomics studies,protein interaction network analyses,hormone signal transduction pathways,genetic improvement strategies,applications of gene editing technologies,molecular basis of stress responses,cross-species functional conservation,and bioinformatics and comparative genomics research.This review highlights the importance of WRKY53 in rice biology and provides new perspectives and strategies for future research and genetic improvement of rice.
基金Project Supported by Jiangxi Provincial Natural Science Foundation(20212ACB206002)。
文摘Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to joint function loss and disability.Signal transducer and activator of transcription 3(STAT3)up-regulates the expression of MMP-13,which degrades collagen Ⅱ.Our previous study found that 5,7,3',4'-tetramethoxyflavone(TMF)exhibited protective effects on OA chondrocytes.This study aims to investigate the protective role of TMF in inhibiting ECM degradation by mediating the Sirt1/STAT3 signaling pathway.Methods:Rat OA models were established by the injection of monosodium iodoacetate(MIA).Hematoxylin&eosin(HE)staining and immunohistochemistry(IHC)analysis were performed.IL-1β stimulated C28/I2 cells were used as OA-like chondrocyte cell model.Western blotting assays were used to determine the protein expression.Results:The expression of MMP-13 was upregulated while type Ⅱ collagen expression is downregulated,and the phosphorylation level of STAT3 is increased in rat OA models.TMF reverses the STAT3-mediated expression of MMP-13 and type v collagen.Activation of STAT3 or inhibition of Sirt1 function attenuates the inhibitory effect of TMF on ECM degradation.Conclusion:TMF can inhibit ECM degradation mediated by the STAT3 signal pathway by activating Sirt1 expression in OA cell and animal models.
基金supported by Research and Innovation Foundation of Wuhan Asia General Hospital,No.2022KYCX1-B10(to FH)the Natural ScienceFoundation of Hubei Province,No.2023AFB550(to FH)+2 种基金the National Natural Science Foundation of China,Nos.32400554(to FH),82371444(to YZ)theGuiding Project of the Scientific Research Program of the Department of Education of Hubei Province,No.B2021016(to FH)the Natural Science Foundationof Hubei Province,No.2024AFB853(to QW).
文摘Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
基金supported by the National Natural Science Foundation of China(32171945,32301760)the Program for Innovative Research Team(in Science and Technology)in University of Henan Province,China(22IRTSTHN023)+2 种基金the Scientific and Technological Research Project of Henan Province,China(242102111116)the National Science Foundation for Postdoctoral Scientists of China(2023M731003)the Postdoctoral Research Subsidize Fund of Henan Province,China(HN2022139)。
文摘Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular level,many small molecules play crucial roles in balancing growth and defense,and stable high yields can be achieved by fine-tuning the responses to external stimuli.Therefore,it is essential to understand the molecular mechanisms underlying plant growth in response to heat stress and how plants can adjust their biological processes to survive heat stress conditions.In this review,we summarize the heat-responsive genetic networks in plants and crop plants based on recent studies.We focus on how plants sense the elevated temperatures and initiate the cellular and metabolic responses that allow them to adapt to the adverse growing conditions.We also describe the trade-off between plant growth and responses to heat stress.Specifically,we address the regulatory network of plant responses to heat stress,which will facilitate the discovery of novel thermotolerance genes and provide new opportunities for agricultural applications.
基金Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases (20MC1920600)Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901)+3 种基金The Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"[Letter of the People's Education of Traditional Chinese Medicine (2019) No.62]Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team [No.3 of Shanghai Education Commission (2022)]Program for Shanghai High-Level Local University Innovation Team (SZY20220315)Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan (SHDC2020CR3090B)。
文摘OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.
基金supported by the Deutsche Forschungsgemeinschaft (ME1922/14-1) to AM。
文摘The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.
文摘OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
基金National Natural Science Foundation of China(U23A20199)Yunnan Revitalization Talent Support Program“Yunling Scholar”and Yunnan Fundamental Research Projects(202201AS070056)。
文摘Ca^(2+)signaling plays crucial roles in plant stress responses,including defense against insects.To counteract insect feeding,different parts of a plant deploy systemic signaling to communicate and coordinate defense responses,but little is known about the underlying mechanisms.In this study,micrografting,in vivo imaging of Ca^(2+)and reactive oxygen species(ROS),quantification of jasmonic acid(JA)and defensive metabolites,and bioassay were used to study how Arabidopsis seedlings regulate systemic responses in leaves after hypocotyls are wounded.We show that wounding hypocotyls rapidly activated both Ca^(2+)and ROS signals in leaves.RBOHD,which functions to produce ROS,along with two glutamate receptors GLR3.3 and GLR3.6,but not individually RBOHD or GLR3.3 and GLR3.6,in hypocotyls regulate the dynamics of systemic Ca^(2+)signals in leaves.In line with the systemic Ca^(2+)signals,after wounding hypocotyl,RBOHD,GLR3.3,and GLR3.6 in hypocotyl also cooperatively regulate the transcriptome,hormone jasmonic acid,and defensive secondary metabolites in leaves of Arabidopsis seedlings,thus controlling the systemic resistance to insects.Unlike leaf-to-leaf systemic signaling,this study reveals the unique regulation of wounding-induced hypocotyl-to-leaf systemic signaling and sheds new light on how different plant organs use complex signaling pathways to modulate defense responses.
基金supported by the National Natural Science Foundation of China(No.82002241)National Key Research and Development Program of China(No.2020YFA0909000)“Clinic Plus”Outstanding Project(No.2024ZY012)from Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine。
文摘Upon encountering external challenges,immune cell recognition of response to pathogens constitutes a pivotal physiological process.Here,we designed and engineering an artificial immune signal transduction system utilizing DNA strands and liposomes to simulate antigen signals presentation,i.e.,the uptake and processing of antigens by antigen-presenting cells(APCs).Through controlled DNA strand displacement reactions,we engineered artificial antigen-presenting cells(mAPCs)that display antigen signals on their surface and mimic phagocytosis.To further simulate antigen presentation,we constructed mimic naïve T cells(mTCs).Then,deoxyribonucleic acid(DNA)ion channels across mTCs membranes,simulating Tcell receptors,were opened by DNA strands on mAPCs mimicking the major histocompatibility complex(MHC),i.e.,MHC molecules that present peptides to the T-cell receptor(TCR)on mTCs(recognition).This allowed Ca^(2+)ions to enter mTCs,increasing calcein fluorescence as activated mTC response indicator.The DNA strands on the surface of A-mAPCs and the Ca^(2+)ions in the solution together act like costimulatory molecules on APCs to trigger responses of mTCs.This simulation of immune signal transduction provides a significant reference value for the construction of bioinspired signal transduction systems and the design of more realistic artificial biological systems.
基金Fujian Natural Science:Study on Potential Protein Targets of Huluan Decotion in the Intervention of Premature Ovarian Failure(No.2021J011173)Major Project Cultivation Plan Project of Ningde Normal University:the Effect of Huluan Decotion on the Decreased Ovarian Reserve Function Induced by Cyclophosphamide is Studied based on Forkhead box L2(No.2019ZDK06)。
文摘OBJECTIVES:To investigate the therapeutic effect of Huluan decotion(护卵汤,HLD)on cyclophosphamideinduced premature ovarian failure(POF)in mice and its regulatory mechanisms.METHODS:Female BALB/c mice were administered cyclophosphamide and administered received different doses of HLD for 28 d.Levels of sex hormone,such as estradiol(E2),follicle stimulating hormone(FSH)and luteinizing hormone(LH)in the sera,were assessed using enzyme-linked immunosorbent assay(ELISA).Follicular structure variances were observed through hematoxylin and eosin(HE)staining,while Forkhead box L2(FOXL2)expression were analyzed via immuneohistochemical staining.The primary mechanism of POF were investigated through Western blot analysis.RESULTS:E2 levels decreased,and FSH and LH levels increased in POF model mice,but these trends were reversed with HLD or premarin administration,the expressions of WNT family member 4(Wnt4),β-Catenin and FOXL2 were downregulated in POF model mice,whereas high expression levels were observed in control mice and other groups.CONCLUSION:HLD effectively treats POF induced with cyclophosphamide in mice by enhancing expressions of Wnt4,β-Catenin and FOXL2.
