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Introduction: Maize stalk rot (MSR), caused by Fusarium graminearum, is the most serious soil borne disease in maize production, seriously affecting maize yield and quality worldwide. Microbial biocontrol agents are the best means of controlling MSR and reducing the use of chemical fungicides, such as Bacillus spp. Methods and results: In the study, a soil-isolated strain B105-8 was identified as B. velezensis (accession No. PP325775.1 and No. PP869695.1), demonstrated a broad spectrum against various pathogens causing maize diseases, which effectively controlled MSR, exhibited a high control efficacy of more than 60% and growth-promoting effect in the pot plant. B105-8 could effectively improve soil urease (S-UE), invertase (S-SC), and catalase (S-CAT) activities. S-NP activity showed an initial increase with a peak of 20,337 nmol/h/g, followed by a decrease, but activity remained significantly better than control treatment with chemical fungicides. The application of B105-8 repaired the damage caused by F. graminearum on soil activity. The antifungal compound B-1, extracted from B105-8, was purified using a protein purifier, revealing inhibitory effects against F. graminearum. Mass spectrometry analysis indicated the potential presence of C14 Bacillomycin, C15 Iturin, C15 Mycosubtilin, C17, and C15 fengycin in B-1. In pot experiments, a 5 µL/mL concentration of B-1 exhibited 69% control on MSR, enhancing maize root elongation, elevation, and fresh weight. At 10 µL/mL, B-1 showed 89.0 and 82.1% inhibition on spore production and mycelial growth, causing hyphal deformities. Discussion: This study presents the innovative use of B. velezensis, isolated from maize rhizosphere in cold conditions to effectively control MSR caused by F. graminearum. The findings highlight the remarkable regional and adaptive characteristics of this strain, making it an excellent candidate to fight MSR in diverse environments. In conclusion, B. velezensis B105-8 demonstrated potential as a biocontrol agent for MSR.
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Background: Drought constitutes a major abiotic stress factor adversely affecting plant growth and productivity. Plant-microbe symbiotic associations have evolved regulatory mechanisms to adapt to environmental stress conditions. However, the interactive effects of different fungi on host growth and stress tolerance under drought conditions remain unclear. Objective: This study explored the effects of varying polyethylene glycol (PEG-6000) concentrations (0%, 15%, 25%, and 35%) on the growth and physiological responses of two ectomycorrhizal fungi (Suillus granulatus (Sg) and Pisolithus tinctorius (Pt)) and two dark septate endophytes (Pleotrichocladium opacum (Po) and Pseudopyrenochaeta sp. (Ps)) isolated from the root system of Pinus tabuliformis. Specifically, the study aimed to evaluate six inoculation treatments, including no inoculation (CK), single inoculations with Sg, Pt, Po, Ps, and a mixed inoculation (Sg: Pt : Po: Ps = 1:1:1:1), on the growth and physiological characteristics of P. tabuliformis seedlings under different water regimes: well-watered at 70% ± 5%, light drought at 50% ± 5%, and severe drought at 30% ± 5% of the maximum field water holding capacity. Results: All four fungi exhibited the capacity to cope with drought stress by enhancing antioxidant activities and regulating osmotic balance. Upon successful root colonization, they increased plant height, shoot biomass, root biomass, total biomass, and mycorrhizal growth response in P. tabuliformis seedlings. Under drought stress conditions, fungal inoculation improved seedling drought resistance by increasing superoxide dismutase and catalase activities, free proline and soluble protein contents, and promoting nitrogen and phosphorus uptake. Notably, mixed inoculation treatments significantly enhanced antioxidant capacity, osmotic adjustment, and nutrient acquisition abilities, leading to superior growth promotion effects under drought stress compared to single inoculation treatments. Conclusion: All four fungi tolerated PEG-induced drought stress, with increased antioxidant enzyme activities and osmotic adjustment substances and they promoted the growth and enhanced drought resistance of P. tabuliformis seedlings.
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This study investigates a brain-computer interface (BCI) system based on an augmented reality (AR) environment and steady-state visual evoked potentials (SSVEP). The system is designed to facilitate the selection of real-world objects through visual gaze in real-life scenarios. By integrating object detection technology and AR technology, the system augmented real objects with visual enhancements, providing users with visual stimuli that induced corresponding brain signals. SSVEP technology was then utilized to interpret these brain signals and identify the objects that users focused on. Additionally, an adaptive dynamic time-window-based filter bank canonical correlation analysis was employed to rapidly parse the subjects' brain signals. Experimental results indicated that the system could effectively recognize SSVEP signals, achieving an average accuracy rate of 90.6% in visual target identification. This system extends the application of SSVEP signals to real-life scenarios, demonstrating feasibility and efficacy in assisting individuals with mobility impairments and physical disabilities in object selection tasks.
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Realidade Aumentada , Interfaces Cérebro-Computador , Eletroencefalografia , Potenciais Evocados Visuais , Humanos , Potenciais Evocados Visuais/fisiologia , Estimulação Luminosa , Interface Usuário-Computador , AlgoritmosRESUMO
One bacterial strain, designated as C22-A2T, was isolated from Lake LungmuCo in Tibet. Cells of strain C22-A2T were long rod-shaped, Gram-stain-negative, non-spore-forming, with positive catalase and oxidase activity. Optimal growth occurred at 20-25 °C, pH 8.0 and with 3.0-7.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene and whole genome sequences revealed that strain C22-A2T belonged to the genus Virgibacillus, showing the highest 16S rRNA gene similarity to Virgibacillus halodenitrificans DSM 10037T (97.6%). The average nucleotide identity values between strain C22-A2T and the type strains of related species in the genus Virgibacillus were less than 74.4% and the digital DNA-DNA hybridization values were less than 20.2%, both below the species delineation thresholds of 95 and 70% respectively. The genome analysis revealed that strain C22-A2T harboured genes responsible for osmotic and oxidative stress, enabling it to adapt to its surrounding environment. In terms of biochemical and physiological characteristics, strain C22-A2T shared similar characteristics with the genus Virgibacillus, including the predominant cellular fatty acid anteiso-C15â:â0, the major respiratory quinone MK-7, as well as the polar lipids phosphatidylglycerol and diphosphatidylglycerol. Based on the comprehensive analysis of phylogenetic, phylogenomic, morphological, physiological and biochemical characteristics, strain C22-A2T is proposed to represent a novel species of the genus Virgibacillus, named as Virgibacillus tibetensis sp. nov. (=CGMCC 1.19202T=KCTC 43426T).
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Lagos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Virgibacillus , Tibet , RNA Ribossômico 16S/genética , Lagos/microbiologia , DNA Bacteriano/genética , Virgibacillus/genética , Virgibacillus/isolamento & purificação , Virgibacillus/classificação , Cloreto de Sódio/metabolismo , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Genoma Bacteriano , Fosfolipídeos/análise , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Vaccines targeting immune checkpoints represent a promising immunotherapeutic approach for solid tumors. However, the therapeutic efficacy of dual targeting immune checkpoints is still unclear in renal carcinoma. METHODS: An adenovirus (Ad) vaccine targeting B7H1 and B7H3 was developed and evaluated for its therapeutic efficacy in subcutaneous, lung metastasis or orthotopic renal carcinoma mouse and humanized models using flow cytometry, Enzyme-linked immunosorbent spot (ELISPOT), cytotoxic T lymphocyte (CTL) killing, cell deletion, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) assays. RESULTS: The Ad-B7H1/B7H3 immunization effectively inhibited tumor growth and increased the induction and percentages of CD8+ T cells in subcutaneous tumor models. The vaccine enhanced the induction and maturation of CD11c+ or CD8+CD11c+ cells, promoting tumor-specific CD8+ T cell immune responses. This was evidenced by increased proliferation of CD8+ T cells and enhanced CTL killing activity. Deletion of CD8+ T cells in vivo abolished the anti-tumor effect of the Ad-B7H1/B7H3 vaccine, highlighting the pivotal role of functional CD8+ T cell immune responses. Moreover, significant therapeutic efficacy of the Ad-B7H1/B7H3 vaccine was observed in lung metastasis, orthotopic, and humanized tumor models through multifunctional CD8+ T cell immune responses. CONCLUSIONS: The Ad vaccine targeting dual immune checkpoints B7H1 and B7H3 exerts a potent therapeutic effect for renal carcinoma and holds promise for solid tumor treatment.
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Adenoviridae , Linfócitos T CD8-Positivos , Vacinas Anticâncer , Carcinoma de Células Renais , Neoplasias Renais , Animais , Humanos , Vacinas Anticâncer/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Camundongos , Linhagem Celular Tumoral , Adenoviridae/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Antígenos B7/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/secundário , Feminino , Camundongos Endogâmicos C57BL , Imunoterapia/métodos , Camundongos Endogâmicos BALB CRESUMO
Our previous studies have highlighted the potential of silver carp hydrolysate (SCH) in managing chronic diseases. Unfortunately, its fishy smell and bitter taste limited consumer acceptance. Prebiotic oligosaccharides are often used as dietary supplements, ignoring their role as carbonyl ligands in the Maillard reaction to enhance food's sensory and antioxidant properties. This study aimed to improve SCH's sensory attributes and investigate its physicochemical properties and antioxidant activities using prebiotic oligosaccharides via the Maillard reaction. The results showed that xylo-oligosaccharide (XOS) had the highest reactivity among the oligosaccharides tested, and it greatly enhanced the taste and flavor of SCH, as well as its antioxidant activities (0.45 to 16.5 times). Specifically, XOS effectively reduced the fishy smell and bitter taste, imparting a caramel-like flavor and overall acceptability to SCH. The improved flavor profile was attributed to the increased presence of sulfur-containing and nitrogen oxide volatile flavor compounds, such as benzothiazole, methional, and furans, which also contributed to antioxidant effects. Sensory evaluation results indicated that SCH obtained from papain exhibited a stronger bitter taste than that obtained from alcalase. Additionally, XOS imparted a reddish-brown color to SCH due to the higher browning intensity. This study is the first to demonstrate that XOS in the Maillard reaction can effectively improve the undesirable flavor and taste of SCH while enhancing its antioxidant activities, providing a theoretical basis for developing SCH as a market-acceptable functional food ingredient.
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Antioxidantes , Carpas , Reação de Maillard , Oligossacarídeos , Prebióticos , Paladar , Antioxidantes/química , Antioxidantes/farmacologia , Animais , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Humanos , Masculino , Feminino , Aromatizantes/química , AdultoRESUMO
The development of simple, rapid, and sensitive methods for detecting pesticide in environmental and food samples holds significant importance. Electrochemiluminescence (ECL) sensing platforms with high resistance to interference and contamination, and reduced consumption of ECL emitters, are highly desirable for such applications. In this work, we present an ECL sensing platform based on a graphitic carbon nitride nanosheets (CNNS) supported vertically ordered mesoporous silica film (VMSF) modified glassy carbon electrode (GCE) for the highly sensitive detection of the environmental pollutant 2,4,6-trichlorophenol (TCP) and the broad-spectrum insecticide prochloraz. Two-dimensional (2D) CNNS were synthesized by exfoliating bulk graphitic carbon nitride (g-C3N4) using concentrated sulfuric acid, serving as a novel conductive and adhesive layer for the growth of a stable VMSF on GCE via an electrochemical assistance self-assembly (EASA) method to prepare VMSF/CNNS/GCE. The electrostatic enrichment capability of VMSF nanochannels for the positively charged ECL emitter tris(2,2'-bipyridyl)ruthenium(ii) (Ru(bpy)3 2+) realized stable and significantly enhanced ECL signals at a low concentration of Ru(bpy)3 2+ (10 µM). Based on the quenching effect of TCP on the ECL signal of Ru(bpy)3 2+, highly sensitive ECL detection of TCP was achieved by the VMSF/CNNS/GCE with a linear range from 10 nM to 0.7 mM and a low detection limit (DL) of 2.2 nM. As the metabolic end product of prochloraz is TCP, indirect ECL detection of prochloraz was also accomplished by measuring the produced TCP. Combined with anti-fouling and anti-interference abilities, as well as signal amplification of VMSF, the developed VMSF/CNNS/GCE sensor enabled the sensitive ECL detection of TCP in pond water and prochloraz in orange peel extract.
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BACKGROUND: Existing literature on the impact of lipid accumulation product (LAP) and visceral adiposity index (VAI) on severe headache or migraine is limited. This study aims to elucidate the association between LAP and VAI and the prevalence of migraine. METHODS: Data for this study were sourced from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). A database-self-administered questionnaire was used to assess severe headache or migraine. A weighted logistic regression model was employed to assess the relationship between LAP and VAI with migraine prevalence. Complementary analytical approaches included subgroup analysis, restricted cubic spline (RCS), and threshold effect analysis to validate the findings. RESULTS: In the end, 4572 people were recruited for the research, including 880 with migraine and 3692 without migraine. Following adjustment for the relevant covariables, weighted logistic regression analysis (OR = 1.409, 95% CI: 1.054, 1.883, P = 0.022; OR = 1.288, 95% CI: 1.010, 1.642, P = 0.042) revealed significantly elevated odds of migraine prevalence in participants within the highest tertile (T3) of LAP and VAI than those in the lowest tertile (T1). The nonlinear association between migraine prevalence and both VAI and LAP was further elucidated through a restricted cubic spline. The threshold analysis pinpointed 2.142 (log-likelihood ratio = 0.016) as the critical inflection point for VAI. Subgroup analysis and interaction testing revealed the significant association was independent in different subgroup factors. CONCLUSIONS: The data indicate a robust association between higher levels of LAP and VAI and an increased prevalence of migraine.
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Cefaleia , Gordura Intra-Abdominal , Produto da Acumulação Lipídica , Transtornos de Enxaqueca , Inquéritos Nutricionais , Humanos , Transtornos de Enxaqueca/epidemiologia , Masculino , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Gordura Intra-Abdominal/metabolismo , Cefaleia/epidemiologia , Cefaleia/fisiopatologia , Prevalência , Adiposidade , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/complicações , Modelos LogísticosRESUMO
Three-dimensional printing technology is a rapid prototyping technology that has been widely used in manufacturing. However, the printing parameters in the 3D printing process have an important impact on the printing effect, so these parameters need to be optimized to obtain the best printing effect. In order to further understand the impact of 3D printing parameters on the printing effect, make theoretical explanations from the dimensions of mathematical models, and clarify the rationality of certain important parameters in previous experience, the purpose of this study is to predict the impact of 3D printing parameters on the printing effect by using machine learning methods. Specifically, we used four machine learning algorithms: SVR (support vector regression): A regression method that uses the principle of structural risk minimization to find a hyperplane in a high-dimensional space that best fits the data, with the goal of minimizing the generalization error bound. Random forest: An ensemble learning method that constructs a multitude of decision trees and outputs the class that is the mode of the classes (classification) or mean prediction (regression) of the individual trees. GBDT (gradient boosting decision tree): An iterative ensemble technique that combines multiple weak prediction models (decision trees) into a strong one by sequentially minimizing the loss function. Each subsequent tree is built to correct the errors of the previous tree. XGB (extreme gradient boosting): An optimized and efficient implementation of gradient boosting that incorporates various techniques to improve the performance of gradient boosting frameworks, such as regularization and sparsity-aware splitting algorithms. The influence of the print parameters on the results under the feature importance and SHAP (Shapley additive explanation) values is compared to determine which parameters have the greatest impact on the print effect. We also used feature importance and SHAP values to compare the importance impact of print parameters on results. In the experiment, we used a dataset with multiple parameters and divided it into a training set and a test set. Through Bayesian optimization and grid search, we determined the best hyperparameters for each algorithm and used the best model to make predictions for the test set. We compare the predictive performance of each model and confirm that the extrusion expansion ratio, elastic modulus, and elongation at break have the greatest influence on the printing effect, which is consistent with the experience. In future, we will continue to delve into methods for optimizing 3D printing parameters and explore how interpretive machine learning can be applied to the 3D printing process to achieve more efficient and reliable printing results.
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BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain. METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models. RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of Ad-AURKA/CDK7 promoted the induction and maturation of dendritic cell subsets and augmented multifunctional CD8+ T-cell antitumor immunity. Furthermore, the vaccine induced a long-lasting antitumor effect by promoting the generation of memory CD8+ T cells. Tumor recovery on CD8+ T-cell depletion underscored the indispensable role of these cells in the observed therapeutic effects. The potent efficacy of the Ad-AURKA/CDK7 vaccine was consistently demonstrated in lung metastasis, orthotopic, and humanized tumor models by inducing multifunctional CD8+ T-cell antitumor immune responses. CONCLUSIONS: Our findings illustrate that the Ad-AURKA/CDK7 vaccine targeting dual kinases AURKA and CDK7 emerges as a promising and effective therapeutic approach for the treatment of solid tumors.
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Aurora Quinase A , Vacinas Anticâncer , Animais , Camundongos , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Adenoviridae , Linhagem Celular Tumoral , Quinase Ativadora de Quinase Dependente de Ciclina , Feminino , Neoplasias/imunologia , Neoplasias/terapia , Vacinas contra Adenovirus/imunologia , Vacinas contra Adenovirus/uso terapêutico , Linfócitos T CD8-Positivos/imunologiaRESUMO
The convenient and sensitive detection of metabolites is of great significance for understanding human health status and drug development. Solid-phase electrochemiluminescence (ECL) enzyme electrodes show great potential in metabolite detection based on the enzyme-catalyzed reaction product hydrogen peroxide (H2O2). Herein, a solid-phase ECL enzyme sensor was fabricated based on a confined emitter and an immobilized enzyme using electrostatic nanocage array, constructing a platform for the sensitive detection of cholesterol. The electrostatic cage nanochannel consists of a bipolar and bilayer vertically aligned mesoporous silica film (bp-VMSF). The upper layer of bp-VMSF is an amino-modified, positively charged VMSF (p-VMSF), and the lower layer is a negatively charged VMSF (n-VMSF). The most commonly used ECL probe tris(bipyridine)ruthenium(II) (Ru(bpy)32+) is fixed in n-VMSF by electrostatic adsorption from n-VMSF and electrostatic repulsion from the upper p-VMSF, generating significantly enhanced and stable ECL signals. The successful preparation of the electrostatic cage was characterized by scanning electron microscopy (SEM) and electrochemical methods. After amino groups on the outer surface of bp-VMSF were derivatized with aldehyde, cholesterol oxidase (ChOx) molecules were covalently immobilized. The successful construction of the enzyme electrode was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). When the corresponding enzyme substrate, cholesterol, was present in the solution, the ECL signal of Ru(bpy)32+ was quenched by the enzyme-catalyzed reaction product H2O2, enabling the high-sensitivity detection of cholesterol. The linear range for detecting cholesterol was from 0.05 mM to 5.0 mM, with a limit of detection (LOD) of 1.5 µM.
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Técnicas Biossensoriais , Colesterol , Técnicas Eletroquímicas , Eletrodos , Colesterol/análise , Enzimas Imobilizadas/química , Medições Luminescentes , Peróxido de Hidrogênio/análise , Humanos , Dióxido de Silício/química , Colesterol OxidaseRESUMO
Electrogenic biofilms, which have attracted considerable attention in simultaneous wastewater treatment and energy recovery in bioelectrochemical systems, are regulated by chemical communication and potassium channel-mediated electrical signaling. However, how these two communication pathways interact with each other has not been thoroughly investigated. This study first explored the roles of chemical communication, including intracellular bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) and extracellular N-acyl-homoserine lactone (AHL)-mediated quorum sensing, in electrogenic biofilm formation through an integrated analysis of transcriptomics and metabolomics. Electrical signaling disruption inhibited the formation and electroactivity of Geobacter sulfurreducens biofilm, which was mainly ascribed to the reduction in biofilm viability and extracellular protein/polysaccharide ratio. The upregulation of expression levels of genes encoding c-di-GMP and AHL synthesis by transcriptomic analysis, and the increased secretion of N-butanoyl-L-homoserine lactone by metabolomic analysis confirmed the enhancement of chemical communication under electrical signaling disruption, thus indicating a compensatory mechanism among different signaling pathways. Furthermore, protein-protein interaction network showed the convergence of different signaling pathways, with c-di-GMP-related genes acting as central bridges. This study highlights the interaction of different signaling pathways, especially the resilience of c-di-GMP signaling to adverse external stresses, thereby laying the foundation for facilitating electrogenic biofilm formation under adverse conditions in practical applications.
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To investigate the impact of low temperature on the quality and flavor of ripe red tomatoes, we analyzed transcriptomes and volatile metabolomes of ripe red fruits stored at 0 °C and 20 °C for 8 days. The results showed that 0 °C maintained the sugar content by increasing the expression of sucrose synthetase (SUS) and sucrose transporter (SUT). Low expression of aroma synthesis-related genes, such as alcohol dehydrogenase 1 (ADH1), amino acid decarboxylase 1 A (AADC1A), and branched-chain amino acid aminotransferase 2 (BCAT2), were associated with reduced levels of pentanal, hexanal, 3-methylbutanal, 2-methylbutanal, and 2-phenylethanol. Additionally, the expression of pectinesterase (PE), beta-galactosidase (ß-GAL), and beta-glucosidase (ß-Glu), as well as phytoene synthase1 (PSY1) involved in carotenoid synthesis, was inhibited, thereby maintaining fruits texture and color. Furthermore, storage at 0 °C induced the expression of numerous genes regulating antioxidant and heat shock proteins, which further preserved the postharvest quality of tomatoes.
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Armazenamento de Alimentos , Frutas , Proteínas de Plantas , Solanum lycopersicum , Compostos Orgânicos Voláteis , Solanum lycopersicum/química , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo , Frutas/química , Frutas/metabolismo , Frutas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Temperatura BaixaRESUMO
IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4-RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype.
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Autoimunidade , Fator de Transcrição Ikaros , Células Th2 , Ubiquitina-Proteína Ligases , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoimunidade/genética , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/imunologia , Doença Relacionada a Imunoglobulina G4/genética , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/patologia , Linhagem , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/imunologia , Células Th2/imunologia , Células Th2/patologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lindera aggregata (Sims) Kosterm is a common traditional herb that has multiple bioactivities. Radix Linderae (LR), the dry roots of Lindera aggregata (Sims) Kosterm, is a traditional Chinese herbal medicine with antioxidant, anti-inflammatory and immunomodulatory properties, first found in Kaibao Era. Norboldine (Nor) is an alkaloid extracted from LR and is one of the primary active ingredients of LR. However, the pharmacological functions and mechanism of Nor in Alzheimer's disease (AD) are still unknown. AIM OF THE STUDY: This study aims to investigate the effect and mechanism of Nor therapy in improving the cognitive impairment and pathological features of 3 × Tg mice. MATERIALS AND METHODS: 3 × Tg mice were treated with two concentrations of Nor for one month and then the memory and cognitive abilities of mice were assessed by novel object recognition experiment and Morris water maze. The impact of Nor on the pathology of ADwere examined in PC12 cells and animal tissues using western blotting and immunofluorescence. Finally, western blotting was used to verify the anti-apoptotic effect of Nor by activating AMPK/GSK3ß/Nrf2 signaling pathway at animal and cellular levels. RESULTS: In this study, we showed that Nor treatment improved the capacity of the learning and memory of 3 × Tg mice and alleviated AD pathology such as Aß deposition. In addition, Nor restored the abnormalities of mitochondrial membrane potential, significantly reduced the production of intracellular ROS and neuronal cell apoptosis. Mechanistically, we combined network pharmacology and experimental verification to show that Nor may exert antioxidant stress and anti-apoptotic through the AMPK/GSK3ß/Nrf2 signaling pathway. CONCLUSION: Our data provide some evidence that Nor exerts a neuroprotective effect through the AMPK/GSK3ß/Nrf2 pathway, thereby improving cognitive impairment in AD model mice. Natural products derived from traditional Chinese medicines are becoming increasingly popular in the process of new drug development and discovery, and our findings provide new perspectives for the discovery of improved treatment strategies for AD.
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Alcaloides , Doença de Alzheimer , Disfunção Cognitiva , Lindera , Extratos Vegetais , Transdução de Sinais , Animais , Masculino , Camundongos , Ratos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Células PC12 , Transdução de Sinais/efeitos dos fármacos , Lindera/química , Extratos Vegetais/administração & dosagem , Alcaloides/administração & dosagemRESUMO
The purpose of this study was to investigate the impact of highoxygen-modified atmospheric packaging (HOMAP) on aroma changes in fresh-cut broccoli during storage and to explore its regulatory mechanisms. The results showed that HOMAP reduced the levels of undesirable aroma substances hexanoic acid, isobutyric acid, cyclopentanone and increased glucosinolate accumulation by inhibiting the expression of arogenate/prephenate dehydratase (ADT), bifunctional aspartate aminotransferase and glutamate/aspartate-prephenate aminotransferase (PAT), thiosulfate/3-mercaptopyruvate Transferase (TST) to reduce the odor of fresh-cut broccoli. HOMAP inhibited the expression of respiratory metabolism related genes 6-phosphate fructokinase 1 (PFK), pyruvate kinase (PK), and NADH-ubiquinone oxidoreductase chain 6 (ND6). In HOMAP group, the low expression of phospholipase C (PLC), phospholipase A1 (PLA1), linoleate 9S-lipoxygenase 1 (LOX1) related to lipid metabolism and the high expression of naringenin 3-dioxygenase (F3H), trans-4-Hydroxycinnamate (C4H), glutaredoxin 3 (GRX3), and thioredoxin 1 (TrX1) in the antioxidant system maintained membrane stability while reducing the occurrence of membrane lipid peroxidation.
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Brassica , Embalagem de Alimentos , Oxigênio , Brassica/química , Brassica/metabolismo , Embalagem de Alimentos/instrumentação , Oxigênio/metabolismo , Oxigênio/análise , Paladar , Odorantes/análise , Proteínas de Plantas/metabolismo , Aromatizantes/química , Aromatizantes/metabolismo , Armazenamento de Alimentos , Conservação de Alimentos/métodosRESUMO
Accurate image segmentation plays a crucial role in computer vision and medical image analysis. In this study, we developed a novel uncertainty guided deep learning strategy (UGLS) to enhance the performance of an existing neural network (i.e., U-Net) in segmenting multiple objects of interest from images with varying modalities. In the developed UGLS, a boundary uncertainty map was introduced for each object based on its coarse segmentation (obtained by the U-Net) and then combined with input images for the fine segmentation of the objects. We validated the developed method by segmenting optic cup (OC) regions from color fundus images and left and right lung regions from Xray images. Experiments on public fundus and Xray image datasets showed that the developed method achieved a average Dice Score (DS) of 0.8791 and a sensitivity (SEN) of 0.8858 for the OC segmentation, and 0.9605, 0.9607, 0.9621, and 0.9668 for the left and right lung segmentation, respectively. Our method significantly improved the segmentation performance of the U-Net, making it comparable or superior to five sophisticated networks (i.e., AU-Net, BiO-Net, AS-Net, Swin-Unet, and TransUNet).
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BACKGROUND: Photon-counting computed tomography (Photon counting CT) utilizes photon-counting detectors to precisely count incident photons and measure their energy. These detectors, compared to traditional energy integration detectors, provide better image contrast and material differentiation. However, Photon counting CT tends to show more noticeable ring artifacts due to limited photon counts and detector response variations, unlike conventional spiral CT. OBJECTIVE: To comprehensively address this issue, we propose a novel feature shared multi-decoder network (FSMDN) that utilizes complementary learning to suppress ring artifacts in Photon counting CT images. METHODS: Specifically, we employ a feature-sharing encoder to extract context and ring artifact features, facilitating effective feature sharing. These shared features are also independently processed by separate decoders dedicated to the context and ring artifact channels, working in parallel. Through complementary learning, this approach achieves superior performance in terms of artifact suppression while preserving tissue details. RESULTS: We conducted numerous experiments on Photon counting CT images with three-intensity ring artifacts. Both qualitative and quantitative results demonstrate that our network model performs exceptionally well in correcting ring artifacts at different levels while exhibiting superior stability and robustness compared to the comparison methods. CONCLUSIONS: In this paper, we have introduced a novel deep learning network designed to mitigate ring artifacts in Photon counting CT images. The results illustrate the viability and efficacy of our proposed network model as a new deep learning-based method for suppressing ring artifacts.
Assuntos
Artefatos , Imagens de Fantasmas , Fótons , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado Profundo , AlgoritmosRESUMO
Bitter melon fruit is susceptible to yellowing, softening, and rotting under room-temperature storage conditions, resulting in reduced commercial value. Nitric oxide (NO) is an important signaling molecule and plays a crucial role in regulating the fruit postharvest quality. In this study, we investigated the effects of NO treatment on changes in sensory and firmness of bitter melon fruit during postharvest storage. Moreover, transcriptomic, metabolomic, and proteomic analyses were performed to elucidate the regulatory mechanisms through which NO treatment delays the ripening and senescence of bitter melon fruit. Our results show that differentially expressed genes (DEGs) were involved in fruit texture (CSLE, ß-Gal, and PME), plant hormone signal transduction (ACS, JAR4, and AUX28), and fruit flavor and aroma (SUS2, LOX, and GDH2). In addition, proteins differentially abundant were associated with fruit texture (PLY, PME, and PGA) and plant hormone signal transduction (PBL15, JAR1, and PYL9). Moreover, NO significantly increased the abundance of key enzymes involved in the phenylpropanoid biosynthetic pathway, thus enhancing the disease resistance and alleviating softening of bitter melon fruit. Finally, differential metabolites mainly included phenolic acids, terpenoids, and flavonoids. These results provide a theoretical basis for further studies on the physiological changes associated with postharvest ripening and senescence of bitter melon fruit. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00110-y.
RESUMO
Hydrogel is a very promising dressing for hemostasis and wound healing due to its good adhesion and long-term moist environment. However, secondary injury caused by tissue adhesion due to homogeneous hydrogel cannot be ignored. The obvious interface existing in Janus hydrogel will weaken its asymmetric function. Here, a hierarchical adhesive polyacrylic acid-polyurushiol water-oil Janus hydrogel (JPs@PAA-PU) without adhesive layer is fabricated by one-pot method in the stabilization of polystyrene@silica-siliver Janus particles (JPs). The morphological structure, mechanical properties, anisotropic chemical composition, and adhesion performance, in vivo, and in vitro hemostatic properties of Janus hydrogel are investigated. Result shows that the obtained Janus hydrogel possesses obvious compartmentalization in microstructure, functional groups, and chemical elements. Janus hydrogel is provided with asymmetric interfacial toughness with top 52.45 ± 2.29 Kpa and bottom 7.04 ± 0.88 Kpa on porcine liver. The adhesion properties of PAA side to tissue, red blood cells and platelets, promoting effect of PU side on coagulation cascade reaction and its physical battier endow Janus hydrogel with shorter hemostatic time and less blood loss than control group. It also exhibits excellent antibacterial effects against Escherichia coli and Staphylococcus aureus (>90%). Janus hydrogel possesses biosafety, providing safety guarantee for clinical applications in the future.