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BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. MATERIALS AND METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. RESULTS: The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7-260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P < 0.0001) and healthy women [49.6 (35.5-78.9) ng/mL, P < 0.0001]. Moesin had an area under the receiver operator characteristic curve (AUC) of 0.929 for predicting LAM diagnosis compared to healthy women (sensitivity 81.0%, specificity 94.6%). The combination of moesin and VEGF-D made a better prediction in differentiating LAM from OCLDs than moesin or VEGF-D alone. Moreover, elevated levels of moesin were related to lymphatic involvement in patients with LAM. Moesin was found negatively correlated with FEV1%pred, FEV1/FVC, and DLCO%pred (P = 0.0181, r = - 0.3398; P = 0.0067, r = - 0.3863; P = 0.0010, r = - 0.4744). A composite score combining moesin and VEGF-D improved prediction for sirolimus treatment, compared with each biomarker alone. CONCLUSION: Higher levels of moesin in serum may indicate impaired lung function and lymphatic involvement in patients with LAM, suggest a more serious condition, and provide clinical guidance for sirolimus treatment.
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Linfangioleiomiomatose , Proteínas dos Microfilamentos , Humanos , Feminino , Linfangioleiomiomatose/diagnóstico , Fator D de Crescimento do Endotélio Vascular , Biomarcadores , SirolimoRESUMO
BACKGROUND: Severe asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear. METHODS: A retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study. RESULTS: A total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations. CONCLUSION: The existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.
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Obstrução das Vias Respiratórias , Asma , Humanos , Sobrepeso/epidemiologia , Qualidade de Vida , Asma/tratamento farmacológico , Obstrução das Vias Respiratórias/epidemiologia , Obesidade/epidemiologiaRESUMO
In most cases, the number of honeybee stings received by the body is generally small, but honeybee stings can still cause serious allergic reactions. This study fully simulated bee stings under natural conditions and used 1H Nuclear Magnetic Resonance (1H NMR) to analyze the changes in the serum metabolome of Sprague-Dawley (SD) rats stung once or twice by honeybees to verify the impact of this mild sting on the body and its underlying mechanism. The differentially abundant metabolites between the blank control rats and the rats stung by honeybees included four amino acids (aspartate, glutamate, glutamine, and valine) and four organic acids (ascorbic acid, lactate, malate, and pyruvate). There was no separation between the sting groups, indicating that the impact of stinging once or twice on the serum metabolome was similar. Using the Principal Component Discriminant Analysis ( PCA-DA) and Variable Importance in Projection (VIP) methods, glucose, lactate, and pyruvate were identified to help distinguish between sting groups and non-sting groups. Metabolic pathway analysis revealed that four metabolic pathways, namely, the tricarboxylic acid cycle, pyruvate metabolism, glutamate metabolism, and alanine, aspartate, and glutamate metabolism, were significantly affected by bee stings. The above results can provide a theoretical basis for future epidemiological studies of bee stings and medical treatment of patients stung by honeybees.
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Mordeduras e Picadas de Insetos , Metaboloma , Ratos Sprague-Dawley , Animais , Abelhas/metabolismo , Ratos , Mordeduras e Picadas de Insetos/sangue , Masculino , Redes e Vias Metabólicas , Análise de Componente PrincipalRESUMO
BACKGROUND: Aroma is one of the most important quality criterion of different honeys and even defines their merchant value. The composition of volatile compounds, especially the characteristic odor-active compounds, contributes significantly to the aroma of honey. Evodia rutaecarpa (Juss) Benth honey (ERBH) is a special honey in China with unique flavor characteristics. However, no work in the literature has investigated the volatile compounds and characteristic odor-active compounds of ERBHs. Therefore, it is imperative to conduct systematic investigation into the volatile profile, odor-active compounds and odor properties of ERBHs. RESULTS: The characteristic fingerprint of ERBHs was successfully constructed with 12 characteristic peaks and a similarity range of 0.785-0.975. In total, 297 volatile compounds were identified and relatively quantified by headspace solid-phase microextraction coupled with gas chromatography quadrupole time-of-flight mass spectrometry, of which 61 and 31 were identified as odor-active compounds by relative odor activity values and GC-olfactometry analysis, respectively, especially the common 22 odor-active compounds (E)-ß-damascenone, phenethyl acetate, linalool, cis-linalool oxide (furanoid), octanal, hotrienol, trans-linalool oxide (furanoid), 4-oxoisophorone and eugenol, etc., contributed significantly to the aroma of ERBHs. The primary odor properties of ERBHs were floral, followed by fruity, herbaceous and woody aromas. The partial least-squares regression results showed that the odor-active compounds had good correlations with the odor properties. CONCLUSION: Identifying the aroma differences of different honeys is of great importance. The present study provides a reliable theoretical basis for the quality and authenticity of ERBHs. © 2023 Society of Chemical Industry.
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Monoterpenos Acíclicos , Cicloexanóis , Evodia , Mel , Compostos de Tritil , Compostos Orgânicos Voláteis , Odorantes/análise , Evodia/química , Mel/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/químicaRESUMO
Gastric carcinoma has serious morbidity and mortality, which seriously threats human health. The studies on gastrointestinal cell biology have shown that the ubiquitination modification that occurs after protein translation plays an essential role in the pathogenesis of gastric carcinoma. Protein ubiquitination is catalyzed by E3 ubiquitin ligase and can regulate various substrate proteins in different cellular pathways. Cullin-RING E3 ligase (CRLs) is a representative of the E3 ubiquitin ligase family, which requires cullin (CUL) neddylation modification for activation to regulate homeostasis of ~20% of cellular proteins. The substrate molecules regulated by CRLs are often involved in many cell progressions such as cell cycle progression, cell apoptosis, DNA damage and repair. Given that CRLs play an important role in modulation of biological activities, so targeting a certain CULs member neddylation may be an attractive strategy for selectively controlling the cellular proteins levels to achieve the goal of cancer treatment. In this review, we will discuss the roles of CULs and Ring protein in gastric carcinoma and summarize the current neddylation modulators for gastric carcinoma treatment.
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Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Proteínas Culina/metabolismo , Inibidores Enzimáticos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitinas/metabolismo , Animais , Antineoplásicos/efeitos adversos , Carcinoma/enzimologia , Carcinoma/patologia , Inibidores Enzimáticos/efeitos adversos , Humanos , Terapia de Alvo Molecular , Proteólise , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
Particulate matter (PM2.5) and cigarette smoke exposure are leading factors contributing to various diseases, especially respiratory diseases. The purpose of this research was to study the effects of PM2.5 and cigarette smoke on glycerol kinase 5 (GK5) expression and the possible mechanisms by which GK5 participates in lipid droplet (LD) synthesis in alveolar epithelial A549 cells. Real-time polymerase chain reaction (RT-PCR) and western blotting have been used for the detection of messenger RNA (mRNA) and protein expression respectively. GK5 overexpressing cells were established by lentivirus transfection, whereby lentiviral vectors deliver the gene into chromosomes, allowing stable expression. Affymetrix microarray analysis, a widely used tool for measuring genome-wide gene expression, has been used to explore differential gene expression profiles. A549 cells stimulated with PM2.5 and cigarette smoke extract (CSE) showed elevated GK5 expression in a dose-dependent manner. Transmission electron microscopy and oil red O staining were used to observe LDs in cells. Further, GK5 overexpressing cells showed increased LDs and upregulation of genes and proteins related to lipogenesis and lipid transportation. Affymetrix microarray analysis revealed that GK5 overexpression resulted in the differential expression of more than 109 genes, which were mainly involved in the regulation of cell death, cell survival, cellular movement and migration, and those involved in cellular growth and proliferation pathways. Overall, this study demonstrates that GK5 is upregulated during PM2.5 and cigarette smoke exposure and induces LD synthesis.
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Glicerol Quinase , Material Particulado , Células A549 , Apoptose , Humanos , Gotículas Lipídicas , Doença Pulmonar Obstrutiva Crônica , FumaçaRESUMO
Interferometric fiber-optic sensors are often organized in the form of large-scale arrays by lending the technique of time division multiplexing (TDM) to reduce the system cost. Discriminating the time windows for different sensor units is the prerequisite to successfully demodulate the sensing message, but it traditionally calls for a very time-consuming manual calibration process. To combat this problem, a novel automatic time window locating method is proposed in this paper. It introduces the concept of shape function and carries out the cross-correlation operation between the shape function and the sensor signal. The shape function is defined as the function whose curve profile reflects the main data characteristics of the sensor signal. The time window information is then extracted from the correlation result. This whole process is carried out automatically by the interrogation controller of the sensor system without any manual intervene. Experiments are conducted to validate this method. The proposed method can greatly reduce the complexity of locating time windows in large-scale TDM sensor arrays, and make the practical use of the TDM scheme much more convenient.
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The Chinese black honey bee is a distinct honey bee subspecies distributed in the Xinjiang, Heilongjiang and Jilin Provinces of China. We conducted a study to investigate the genetic origin and the parasite/pathogen profile on Chinese black honeybees. The phylogenetic analysis indicated that Chinese black honeybees were two distinct groups: one group of bees formed a distinct clade that was most similar to Apis mellifera mellifera and the other group was a hybrid of the subspecies, Apis mellifera carnica, Apis mellifera anatolica and Apis mellifera caucasica. This suggests that the beekeeping practices might have promoted gene flow between different subspecies. Screening for pathogens and parasites showed that Varroa destructor and viruses were detected at low prevalence in Chinese black honeybees, compared with Italian bees. Further, a population of pure breeding black honeybees, A. m. mellifera, displayed a high degree of resistance to Varroa. No Varroa mites or Deformed wing virus could be detected in any examined bee colonies. This finding suggests that a population of pure breeding Chinese black honeybees possess some natural resistance to Varroa and indicated the need or importance for the conservation of the black honeybees in China.
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Abelhas/parasitologia , Resistência à Doença , Variação Genética , Varroidae/fisiologia , Animais , Sequência de Bases , Abelhas/classificação , Abelhas/genética , Abelhas/virologia , China , Dados de Sequência Molecular , Filogenia , Prevalência , Análise de Sequência de DNA/veterinária , Especificidade da EspécieRESUMO
How to maintain the balanced stability and resilient development of rural systems is an important issue that needs urgent attention in the field of sustainable rural development at present. In this paper, the entropy method, spatial autocorrelation model, and Geodetector were used to explore the rural resilience level, spatial distribution characteristics, and driving factors of 31 cities in the urban agglomerations in the middle reaches of the Yangtze River (UAMRYR), and to put forward corresponding policy suggestions. The results are as follows: (1) From 2005 to 2020, rural resilience in the UAMRYR showed an upward trend with an average annual growth rate of 8.26%. The ranking of the three major urban agglomerations is Changsha-Zhuzhou-Xiangtan urban agglomerations > Wuhan urban agglomerations > Poyang Lake urban agglomerations. (2) During the study period, the spatial distribution of rural resilience gradually developed from a negative correlation to a strong positive correlation and generally showed the characteristics of high in the west and low in the east. (3) The urbanization rate, the size and structure of the economy, the difference in consumption and income between urban and rural areas, the local fiscal revenue, and the number of village committees are the key factors affecting the level of rural resilience. On this basis, we proposed policy recommendations to improve the economic, social, and ecological resilience of rural areas in the UAMRYR. The findings of this paper are expected to provide insights into the policy formulation of China's rural revitalization strategy.
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Resiliência Psicológica , Rios , China , Cidades , EntropiaRESUMO
High pressure processing is a safe and green novel non-thermal processing technique for modulating food protein aggregation behavior. However, the systematic relationship between high pressure processing conditions and protein deaggregation has not been sufficiently investigated. Major royal jelly proteins, which are naturally highly fibrillar aggregates, and it was found that the pressure level and exposure time could significantly promote protein deaggregation. The 100-200 MPa treatment favoured the deaggregation of proteins with a significant decrease in the sulfhydryl group content. Contrarily, at higher pressure levels (>400 MPa), the exposure time promoted the formation of disordered agglomerates. Notably, the inter-conversion of α-helix and ß-strands in major royal jelly proteins after high pressure processing eliminates the solvent-free cavities inside the aggregates, which exerts a 'collapsing' effect on the fibrillar aggregates. Furthermore, the first machine learning model of the high pressure processing conditions and the protein deaggregation behaviour was developed, which provided digital guidance for protein aggregation regulation.
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Ácidos Graxos , Proteínas de Insetos , Pressão , Agregados Proteicos , Proteínas de Insetos/química , Ácidos Graxos/química , Animais , Manipulação de Alimentos , Abelhas/químicaRESUMO
Ionic conductive elastomers (ICEs) exhibit a compelling combination of ionic conductivity and elastic properties, rendering them excellent candidates for stretchable electronics, particularly in applications like sensing devices. Despite their appeal, a significant challenge lies in the reprocessing of ICEs without compromising their performance. To address this issue, we propose a strategy that leverages covalent adaptable networks (CANs) for the preparation of ICEs. Specifically, ß-amino ester bonds as dynamic motifs are incorporated into a poly(ethylene oxide) network containing lithium bis(trifluoromethane) sulfonimide (LiTFSI) salt. LiTFSI-containing ß-amino ester networks (LBAEs) exhibit superb transparency (94%), thermal stability (>280 °C), and modest conductivity (0.00576 mS·cm-1 at 20 °C), and some LBAEs maintain operational capability across a wide temperature range (-20 to 100 °C). By regulating the lithium salt content, the mechanical properties, conductivities, and viscoelastic behaviors can be tailored. Benefiting from these features, LBAEs have been successfully applied in sensing devices for monitoring human motion (e.g., finger bending, swallowing, and clenching). Notably, even after four reprocessing cycles, LBAEs demonstrate structural integrity and maintain their operational capability. This novel approach represents a promising solution to the reprocessing challenges associated with flexible conductive devices, demonstrating the successful integration of CANs and ICEs.
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With growing concerns about postharvest spoilage of fruits, higher requirements have been placed on high-performance and sustainable active packaging materials. In this study, we prepared curcumin-based functional composite films using chitosan (CS) and Tenebrio molitor larvae protein (TMP) as the substrates. The effects of curcumin concentration on the structural and physicochemical properties of the composite films were determined. Curcumin was equally distributed in the polymer film through physical interactions. Furthermore, the curcumin composite film with 0.3 % addition exhibited a 27.39 % increase in elongation at break (EBA), a 37.04 % increase in the water vapor barrier, and strong UV-blocking properties and antioxidant activity compared with the control film (CS/TMP). The degradation experiment of the composite film on natural soil revealed that the composite film exhibited good biodegradability and environmental protection. Furthermore, the applicability of functional composite films for preserving blueberries was investigated. Compared with the control film and polyethylene (PE) films, the prepared composite films packaging treatment reduced the decay rate and weight loss rate of blueberries during storage, delayed softening and aging, and maintained the quality of blueberries. Using sustainable protein resources (TMP) and natural polysaccharides as packaging materials provides an economically, feasible and sustainable way to achieve the functional preservation of biomass materials.
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Antioxidantes , Mirtilos Azuis (Planta) , Quitosana , Curcumina , Embalagem de Alimentos , Conservação de Alimentos , Larva , Tenebrio , Animais , Quitosana/química , Quitosana/farmacologia , Curcumina/química , Curcumina/farmacologia , Tenebrio/química , Tenebrio/efeitos dos fármacos , Embalagem de Alimentos/métodos , Mirtilos Azuis (Planta)/química , Antioxidantes/farmacologia , Antioxidantes/química , Conservação de Alimentos/métodos , Larva/efeitos dos fármacos , Proteínas de Insetos/químicaRESUMO
Mechanical stretching is commonly used for mesogen alignment which is essential for the muscle-like actuations of liquid crystal elastomers (LCEs). Despite the simplicity of the method, the mesogens are typically aligned in the stretching direction, limiting exclusively the LCE to an actuation mode of cooling-induced elongation. Here, we design an interpenetrating double network consisting of an LCE network and an elastomer network, with one polymerized network stretched before the polymerization of the other network. Depending on the polymerization sequence of the two networks, the double network shows two opposite actuation modes, namely, the conventional cooling-induced elongation or an unusual cooling-induced contraction. Strategic integration of the two opposite behaviors into the same LCE leads to sophisticated actuation difficult to achieve with a conventional LCE design. Coupled with 3D printing, geometrically complexed LCEs with diverse multimodal four-dimensional actuation behaviors are illustrated. Our work expands the design scope of LCE actuators and their potential device applications.
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BACKGROUND: The effect of fibroblast growth factor 10 (Fgf10) against allergic asthma has remained unclear, despite its importance in lung development and homeostasis maintenance. The purpose of this study was to investigate the protective effect and potential mechanism of Fgf10 on asthma. METHOD: House Dust Mite (HDM)-induced asthma mice were administered recombinant Fgf10 intranasally during activation. Flow cytometry and ELISA were performed to determine type of inflammatory cells and type 2 cytokines levels in bronchoalveolar lavage fluid (BALF). Hematoxylin and eosin (H&E) and periodic acid - Schiff (PAS) staining of lung sections were conducted to evaluate histopathological assessment. Transcriptome profiling was analyzed using RNA-seq, followed by bioinformatics and network analyses to investigate the potential mechanisms of Fgf10 in asthma. RT-qPCR was also used to search for and validate differentially expressed genes in human Peripheral Blood Mononuclear Cells (PBMCs). RESULTS: Exogenous administration of Fgf10 alleviated HDM-induced inflammation and mucus secretion in lung tissues of mice. Fgf10 also significantly inhibited the accumulation of eosinophils and type 2 cytokines (IL-4, IL-5, and IL-13) in BALF. The PI3K/AKT/NF-κB pathway may mediate the suppressive impact of Fgf10 on the asthma inflammation. Through RNA-seq analysis, the intersection of 71 differentially expressed genes (DEGs) was found between HDM challenge and Fgf10 treatment. GO and KEGG enrichment analyses indicated a strong correlation between the DEGs and different immune response. Immune infiltration analysis predicted the differential infiltration of five types of immune cells, such as NK cells, dendritic cells, monocytes and M1 macrophages. PPI analysis determined hub genes such as Irf7, Rsad2, Isg15 and Rtp4. Interestingly, above genes were consistently altered in human PBMCs in asthmatic patients. CONCLUSION: Asthma airway inflammation could be attenuated by Fgf10 in this study, suggesting that it could be a potential therapeutic target.
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Asma , NF-kappa B , Animais , Humanos , Camundongos , Asma/tratamento farmacológico , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Fator 10 de Crescimento de Fibroblastos/farmacologia , Fator 10 de Crescimento de Fibroblastos/uso terapêutico , Fator 10 de Crescimento de Fibroblastos/metabolismo , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
The glands of bees are responsible for generating and secreting various biologically active substances that significantly impact bee physiological health and adaptability. This study aimed to investigate the effects of adding citric acid (CA) to bee feed on gland development and royal jelly quality. By formulating feed with varying proportions of CA, evaluation was undertaken of pollen feeding by honeybees under laboratory conditions, along with the impact of CA on the development of major glands, to determine suitable addition proportions. Further optimization of the CA proportion involved feeding colonies and evaluating royal jelly production and quality. The results indicated that feed containing 0.75% CA significantly extended the lifespan of bees and increased their pollen consumption. Gland development in bees showed a positive correlation with CA addition within the range of 0.25% to 0.75%, especially at 0.50% and 0.75%, which notably accelerated the development of mandibular, hypopharyngeal, and cephalic salivary glands, with active proliferation and differentiation of glandular cells and maintenance of normal gland size and morphology. CA added to feed stimulated vigorous secretion of wax glands in worker bees, resulting in prolific wax construction. Colonies consuming feed containing 0.50% CA produced royal jelly with significantly reduced moisture and total sugar content and increased levels of 10-HDA, total phenolic acids, total proteins, and acidity. These findings demonstrate that CA consumption significantly prolongs bee lifespan, increases consumption, promotes gland development, and enhances royal jelly quality. This research provides theoretical guidance for beekeeping practices and feed development, contributing to the sustainable advancement of apiculture.
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Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, ·OH, O2-, 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.
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Inseticidas , Praguicidas , Gases em Plasma , Humanos , Abelhas , Animais , Camundongos , Inseticidas/química , Espécies Reativas de Oxigênio , Estrutura Molecular , Peróxido de Hidrogênio , Neonicotinoides/química , Nitrocompostos/química , Nitrocompostos/farmacologiaRESUMO
Exposure to particulate matter (PM) can cause airway inflammation and worsen various airway diseases. However, the underlying molecular mechanism by which PM triggers airway inflammation has not been completely elucidated, and effective interventions are lacking. Our study revealed that PM exposure increased the expression of histone deacetylase 9 (HDAC9) in human bronchial epithelial cells and mouse airway epithelium through the METTL3/m6A methylation/IGF2BP3 pathway. Functional assays showed that HDAC9 upregulation promoted PM-induced airway inflammation and activation of MAPK signaling pathway in vitro and in vivo. Mechanistically, HDAC9 modulated the deacetylation of histone 4 acetylation at K12 (H4K12) in the promoter region of dual specificity phosphatase 9 (DUSP9) to repress the expression of DUSP9 and resulting in the activation of MAPK signaling pathway, thereby promoting PM-induced airway inflammation. Additionally, HDAC9 bound to MEF2A to weaken its anti-inflammatory effect on PM-induced airway inflammation. Then, we developed a novel inhaled lipid nanoparticle system for delivering HDAC9 siRNA to the airway, offering an effective treatment for PM-induced airway inflammation. Collectively, we elucidated the crucial regulatory mechanism of HDAC9 in PM-induced airway inflammation and introduced an inhaled therapeutic approach targeting HDAC9. These findings contribute to alleviating the burden of various airway diseases caused by PM exposure.
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Epigênese Genética , Histona Desacetilases , Material Particulado , Regulação para Cima , Animais , Material Particulado/toxicidade , Humanos , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Epigênese Genética/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Camundongos , Fosfatases de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Inflamação , Nanopartículas/química , Nanopartículas/toxicidade , Camundongos Endogâmicos C57BL , Linhagem Celular , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , MasculinoRESUMO
Oxidative stress and endoplasmic reticulum stress (ERS) was associated with the development of asthma. Edaravone (EDA) plays a classical role to prevent the occurrence and development of oxidative stress-related diseases. Herein, we investigated the involvement and signaling pathway of EDA in asthma, with particular emphasis on its impact on type 2 innate lymphoid cells (ILC2) and CD4+T cells, and then further elucidated whether EDA could inhibit house dust mite (HDM)-induced allergic asthma by affecting oxidative stress and ERS. Mice received intraperitoneally injection of EDA (10 mg/kg, 30 mg/kg), dexamethasone (DEX) and N-acetylcysteine (NAC), with the latter two used as positive control drugs. DEX and high dose of EDA showed better therapeutic effects in alleviating airway inflammation and mucus secretion in mice, along with decreasing eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) than NAC. Further, the protein levels of IL-33 in lung tissues were inhibited by EDA, leading to reduced activation of ILC2s in the lung. EDA treatment alleviated the activation of CD4+ T cells in lung tissues of HDM-induced asthmatic mice and reduced Th2 cytokine secretion in BALF. ERS-related markers (p-eIF2α, IRE1α, CHOP, GRP78) were decreased after treatment of EDA compared to HDM group. Malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) were detected to evaluate the oxidant stress in lung tissues. EDA showed a protective effect against oxidant stress. In conclusion, our findings demonstrated that EDA could suppress allergic airway inflammation by inhibiting oxidative stress and ERS, suggesting to serve as an adjunct medication for asthma in the future.
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Asma , Imunidade Inata , Camundongos , Animais , Edaravone/farmacologia , Edaravone/uso terapêutico , Citocinas/metabolismo , Endorribonucleases/metabolismo , Peróxido de Hidrogênio/farmacologia , Linfócitos , Proteínas Serina-Treonina Quinases/metabolismo , Asma/metabolismo , Pulmão , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Estresse Oxidativo , Oxidantes/farmacologia , Pyroglyphidae/metabolismo , Modelos Animais de DoençasRESUMO
A novel technique was proposed for processing silkworm pupae by combining plasma- activated water (PAW) with ultrasound (US). The microbial diversity and quality characteristics of the silkworm pupae were also evaluated. The results of the microbial diversity analysis indicated that PAW combined with US treatment significantly reduced the relative abundance of Streptococcaceae, Leuconostocaceae, and Acetobacteraceae from 32%, 18% and 16% to 27%, 11% and 11%, respectively. Microstructural analysis demonstrated that the collapse of the internal structure of chitin in silkworm pupae facilitated the release of nutrients and flavour compounds including fatty acids, water-soluble proteins (WSP), amino acids, phenolics, and volatile compounds. Furthermore, the increase in antioxidant capacity and the decrease in catalase activity and malondialdehyde content confirmed the mechanism of quality change. These findings provide new insights into the possible mechanism of PAW combined with US to improve the quality of edible insects.
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Bombyx , Pupa , Água , Animais , Pupa/microbiologia , Água/química , Bombyx/química , Ondas Ultrassônicas , Fenômenos Químicos , Antioxidantes/química , Antioxidantes/farmacologia , BiodiversidadeRESUMO
With the development of beekeeping, the risk of bee stings in humans is increasing. Severe and life-threatening toxic reactions can occur after multiple bee stings, and their pathogenesis has not been elucidated. To understand the effect of multiple bees (Apis mellifera) stings on the organism in a short period, we stung rats once and five times, respectively. Serum and organs were obtained after 3 h for analysis. The results indicated that skin erythema was more pronounced and hemolysis was more severe as the number of puncture wounds increased. After being stung by five bees, rats had dramatically higher serum levels of direct bilirubin, aspartate aminotransferase, creatine kinase and lactate dehydrogenase, producing more differential metabolites that affected mainly four metabolic pathways. In addition, the liver, kidney and heart showed significant congestion and inflammation. This study helps explain the organism's clinical response to bee venom and may be valuable in treating toxic reactions following bee stings.