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Excessive crowding in the visual periphery has been demonstrated in children with developmental dyslexia (DD). However, less is known about crowding in the fovea, even though foveal crowding is at least equally important, as reading is mostly accomplished through foveal vision. Here we used a special set of digit stimuli (Pelli fonts) to measure foveal crowding in DD and DD + ADHD children, and compared it to that in TD (typically developing) and ADHD children. We also used the Chinese reading acuity charts (C-READ) to assess the maximum reading speed and reading acuity, along with tests to evaluate cognitive attributes including phonological awareness, rapid automatized naming, morphological awareness, and orthographic knowledge. The results indicate significantly stronger foveal crowding in the DD and DD + ADHD groups, as well as in the ADHD group, than in the TD group. Furthermore, the DD and DD + ADHD groups exhibited poorer maximum reading speed and reading acuity compared to the ADHD and TD groups. Within the two DD groups, the slower maximum reading speed and higher reading acuity can be predicted by stronger foveal crowding. In addition, the DD and DD + ADHD groups performed the worst in four cognitive skills, with the DD group showing negative correlations between foveal crowding and performances across all these skills. Our findings thus move beyond previously well-documented peripheral crowding in dyslexia, and the easy administration of the Pelli-font-based crowding test may be useful for early diagnosis of developmental dyslexia in young children.
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Alzheimer's disease (AD) is a common neurodegenerative disease with the main manifestations of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an important role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory storage,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major pathological factor in the occurrence and development of AD.This article reviews the role and research progress in intracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloid ß,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling pathways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflammation.
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Doença de Alzheimer , Cálcio , Homeostase , Doença de Alzheimer/metabolismo , Humanos , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Sinalização do Cálcio/fisiologia , Mitocôndrias/metabolismo , Proteínas tau/metabolismo , Autofagia/fisiologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Neurônios/metabolismo , FosforilaçãoRESUMO
OBJECTIVE: Radiation therapy is applied in the treatment of head and neck cancer patients. However, oral-health-related side effects like hyposalivation and a higher prevalence of caries have been shown. This study aims to assess the influence of different radiotherapy doses on the mechanical properties, roughness, superficial microstructure, and crystallinity of the enamel and dentin of human premolar teeth. METHODS: Specimens (nâ¯= 25) were categorized into five groups based on the radiation dose received (0, 10, 30, 50, and 70â¯Gy). The enamel and dentin of these specimens were subjected to a microhardness tester, profilometer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and Xray diffraction (XRD) before and after different irradiation doses and compared to hydroxylapatite in each group. The data were analyzed using repeated-measures analysis of variance (ANOVA). RESULTS: Therapeutic radiation doses of 30, 50, and 70â¯Gy led to a decrease in the microhardness and an increase in the average roughness of the enamel, and rougher surfaces were observed in the mixed three-dimensional images. Moreover, in the dentin, a similar outcome could be observed for more than 10â¯Gy. The main crystalline phase structure remained hydroxylapatite, but the crystallinity decreased and the crystalline size increased above 10â¯Gy. The superficial micromorphology revealed granulation, fissures, and cracks in a dose-dependent manner. Radiation below 70â¯Gy had little effect on the hydroxylapatite concentration during the whole experiment. CONCLUSION: Above a radiation dose of 30â¯Gy, the micromorphology of the tooth enamel changed. This occurred for dentin above 10â¯Gy, which indicates that dentin is more sensitive to radiotherapy than enamel. The radiation dose had an effect on the micromorphology of the hard tissues of the teeth. These results illustrate the possible mechanism of radiation-related caries and have guiding significance for clinical radiotherapy.
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This paper presents the design of a Lyapunov matrix-based adaptive resilient controller for unmanned marine vehicles (UMVs) under state-dependent sensor attacks, input-dependent thruster attacks, and time delays. Different from the thruster attack model that depends on state information, the thruster attack model studied in this paper is related to control input, that is, the input-dependent thruster attacks. This implies that the designed correction signal is also affected by the attacks. To mitigate the impact of the considered sensor attacks and thruster attacks on UMVs, an adaptive mechanism is employed to estimate the attack factors. Furthermore, a Lyapunov matrix-based complete-type Lyapunov-Krasovskii functional (LKF) is introduced, in which more comprehensive time delay information are considered. Based on this, linear matrix inequality (LMI) method and Jensen's inequality are used to obtain sufficient conditions for the existence of the controller. The proposed controller guarantees that the state errors of UMVs converge asymptotically to zero with the adaptive H∞ performance index no larger than γ0. Finally, the efficacy of the proposed approach is verified by simulation results.
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Due to high humification, hyperthermophilic composting products (HP) show potential for remediating heavy metal pollution. However, the interaction between HP and heavy metals remains unclear. This study investigated the adsorption mechanism and soil remediation effect of HP on heavy metals. The results showed that the maximum adsorption capacity of HP increased by an average of 30.74 % compared to conventional composting products. HP transformed 34.87 % of copper, 42.55 % of zinc, and 35.63 % of lead from exchangeable and reducible forms into residual and oxidizable forms, thus reducing the soil risk level. In conclusion, HP significantly enhanced the adsorption of heavy metals and their transformation from unstable to stable forms, primarily due to the higher content of hydroxyl and carboxyl groups. This study aims to demonstrate the effectiveness of HP for remediating heavy metal pollution and to enhance the understanding of the underlying mechanism, which lays a foundation for waste utilization.
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Compostagem , Metais Pesados , Poluentes do Solo , Adsorção , Poluentes do Solo/química , Compostagem/métodos , Solo/química , Biodegradação Ambiental , Recuperação e Remediação Ambiental/métodosRESUMO
As an atom-economical reaction, the direct generation of dimethyl carbonate (DMC) and ethylene glycol (EG) via the transesterification of CH3OH and ethylene carbonate (EC) has several promising applications, but the exploration of carriers with high specific surface areas and novel heterogeneous catalysts with more basic sites remains a long-standing research challenge. For this purpose, herein, a nitrogen-doped mesoporous carbon (NMC, 439 m2/g) based K-O2 Lewis base catalyst (K-O2/NMC) with well-dispersed strongly basic sites (2.23 mmol/g, 84.5%) was designed and synthesized. The compositions and structures of NMC and K-O2/NMC were comprehensively investigated via Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, CO2 temperature-programmed desorption, and contact angle measurements. The optimal structural configuration and electron cloud distribution of the K-O2/NMC catalyst were simulated using first-principles calculations. The electron transfer predominantly manifested as a flow from K-O to C-O/C-N, and the interatomic interactions between each atom were enhanced and exhibited a tendency for a more stable state after redistribution. Furthermore, the adsorption energies (Eads) of CH3OH at K-O-O and K-O-N sites were -1.4185 eV and -1.3377 eV, respectively, and the O atom in CH3OH exhibited a stronger adsorption tendency for the K atom at the K-O-O site. Under the optimal conditions, the EC conversion, DMC/EG selectivity, and turnover number/frequency were 80.9%, 98.6%/99.4%, and 40.5/60.8 h-1, respectively, with a reaction rate constant (k) of 0.1005 mol/(L·min). Results showed that the heterogeneous K-O2/NMC catalyst prepared herein greatly reduced the reaction cost while guaranteeing the catalytic effect, and the whole system required a lower reaction temperature (65 °C), a shorter reaction time (40 min), and a lower catalyst amount (2.0 wt % of EC). Therefore, K-O2/NMC can be used as a catalyst in different transesterification reactions.
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In order to improve the flavor profiles, food security, probiotic effects and shorten the fermentation period of traditional fermented foods, lactic acid bacteria (LAB) were often considered as the ideal candidate to participate in the fermentation process. In general, LAB strains possessed the ability to develop flavor compounds via carbohydrate metabolism, protein hydrolysis and amino acid metabolism, lipid hydrolysis and fatty acid metabolism. Based on the functional properties to inhibit spoilage microbes, foodborne pathogens and fungi, those species could improve the safety properties and prolong the shelf life of fermented products. Meanwhile, influence of LAB on texture and functionality of fermented food were also involved in this review. As for the adverse effect carried by environmental challenges during fermentation process, engineering strategies based on exogenous addition, cross protection, and metabolic engineering to improve the robustness and of LAB were also discussed in this review. Besides, this review also summarized the potential strategies including microbial co-culture and metabolic engineering for improvement of fermentation performance in LAB strains. The authors hope this review could contribute to provide an understanding and insight into improving the industrial functionalities of LAB.
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Fermentação , Microbiologia de Alimentos , Lactobacillales , Engenharia Metabólica , Engenharia Metabólica/métodos , Lactobacillales/metabolismo , Probióticos/metabolismo , Alimentos Fermentados/microbiologiaRESUMO
Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.
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Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Humanos , Animais , Hormônios/metabolismo , Hormônios/uso terapêutico , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêuticoRESUMO
In this study, the novel polysaccharides named HSP-0 M and HSP-0.1 M were successfully purified from Huangshui (HS), and their structural properties and bioactivities were investigated. Structural analysis revealed that HSP-0 M had a molecular weight of 493.87 kDa and was composed of arabinose, galactose, glucose, xylose, and mannose in a molar ratio of 1.48:1.09:26.52:1.33:1.00. On the other hand, HSP-0.1 M was made up of fructose, arabinose, galactose, glucose, xylose, mannose, ribose, galacturonic acid and glucuronic acid in a ratio of 2.67:26.00:29.10:36.83:16.22:30.53:1.00:1.43:3.64 with a molecular weight of 157.6 kDa. Methylated and 2D NMR analyses indicated that T-Glcp-(1 â 4)-Glcp-(1 â 2)-Glcp-(1 â 3)-Glcp was the primary chain of HSP-0 M, and the backbone of HSP-0.1 M was made up of â3)-Galp-(1 â 6)-Manp-(1 â 3)-Glcp-(1 â 6)-Glcp-(1 â 2)-Manp-(1 â 6)-Glcp-(1 â 3)-Galp. Morphological research showed that both polysaccharides were homogeneous as well as exhibit a web-like structure and an irregular lamellar structure. Furthermore, HSP-0 M demonstrated the capacity to safeguard Lactococcus lactis from damage caused by low temperatures and freeze-drying, while HSP-0.1 M exhibited noteworthy antioxidant activity. These results established a theoretical foundation for the applications of HSPs in food products, cosmetics, and medicines.
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Antioxidantes , Peso Molecular , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Monossacarídeos/análise , Monossacarídeos/química , MetilaçãoRESUMO
Dilated cardiomyopathy (DCM) is a primary cause of heart failure (HF), with the incidence of HF increasing consistently in recent years. DCM pathogenesis involves a combination of inherited predisposition and environmental factors. Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with endogenous hormone action and are capable of targeting various organs, including the heart. However, the impact of these disruptors on heart disease through their effects on genes remains underexplored. In this study, we aimed to explore key DCM-related genes using machine learning (ML) and the construction of a predictive model. Using the Gene Expression Omnibus (GEO) database, we screened differentially expressed genes (DEGs) and performed enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to DCM. Through ML techniques combining maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) logistic regression, we identified key genes for predicting DCM (IL1RL1, SEZ6L, SFRP4, COL22A1, RNASE2, HB). Based on these key genes, 79 EDCs with the potential to affect DCM were identified, among which 4 (3,4-dichloroaniline, fenitrothion, pyrene, and isoproturon) have not been previously associated with DCM. These findings establish a novel relationship between the EDCs mediated by key genes and the development of DCM.
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Cardiomiopatia Dilatada , Disruptores Endócrinos , Cardiopatias , Humanos , Coração , Biologia Computacional , Disruptores Endócrinos/toxicidade , Aprendizado de MáquinaRESUMO
Studies have confirmed that the intake of nonylphenol (NP) can increase nasal symptoms, eosinophils, and Th2 responses in allergic rhinitis (AR) mice. However, the molecular mechanism of NP exacerbating AR inflammatory response remains unclear. Recent data suggest that NOD-like receptor 3 (NLRP3) inflammasome-mediated pyroptosis contributes to AR development. To investigate the effects of NP on NLRP3 inflammasomes and pyroptosis, an AR mouse model induced by ovalbumin (OVA) was established and treated with 0.5 mg/kg/d NP every other day. Nasal symptoms were evaluated after the final OVA instillation. Mast cells and Eosinophils in the nasal mucosa were observed using toluidine blue and Sirius red staining, respectively. The levels of NLRP3, Caspase-1, ASC, phospho-nuclear factor kappa B (NF-κB) p65, interleukin (IL)-6, TNF-α, IL-18, GSDMD and IL-1ß, were assessed by using immunohistochemical staining, ELISA, quantitative real-time PCR, or Western blot. Exposure to NP aggravates AR symptoms and promotes eosinophils, mast cells, and inflammatory factors release, along with significantly increased of NF-κB, NLRP3, Caspase-1, ASC, and GSDMD. It was concluded that NP exposure promotes NLRP3 inflammasome and GSDMD-mediated pyroptosis of the nasal mucosa. Targeted of NLRP3 and GSDMD-mediated pyroptosis may be a novel therapeutic strategy for AR exposed to NP.
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Inflamassomos , Fenóis , Rinite Alérgica , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , NF-kappa B , Proteínas NLR , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/tratamento farmacológico , Interleucina-6 , CaspasesRESUMO
In this work, Rosa roxburghii Tratt fruit polysaccharides (RPs) were extracted by ultrasound-assisted enzymatic method. The highest extraction yield of RPs was 4.78⯱â¯0.10â¯% under the optimal extraction conditions. Two purified fractions named RP1 and RP3 were obtained and systematically characterized by a combination strategy of FT-IR, monosaccharide composition, molecular weight distribution, methylation and 2D NMR spectroscopy analyses. Structural analysis showed that the main chain of RP1 was composed of rhamnogalacturonan type I (RG-I), while the side chains were rich in arabinogalactan and galactose. RP3 was composed of long homogalacturonan (HG) backbone interspersed with alternating sequences of RG-I domains, with galactose and arabinose side chains. RP1 and RP3 induced apoptosis of MCF-7 cells in a dose dependent manner in vitro especially for RP1, and had no effect on L929 cells. Furthermore, the possible anticancer mechanisms were revealed, and results suggested that RP1 induced apoptosis through ROS-dependent pathway and mitochondrial pathway. The results of this work not only provided an efficient extraction method and theoretical basis for the application of RPs, but also may contribute to develop novel functional foods or pharmaceutical products for the prevention and treatment of human breast cancer disease.
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Rosa , Humanos , Rosa/química , Galactose/análise , Frutas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/químicaRESUMO
BACKGROUND: Yeast is often used to build cell factories to produce various chemicals or nutrient substances, which means the yeast has to encounter stressful environments. Previous research reported that unsaturated fatty acids were closely related to yeast stress resistance. Engineering unsaturated fatty acids may be a viable strategy for enhancing the stress resistance of cells. RESULTS: In this study, two desaturase genes, OLE1 and FAD2 from Z. rouxii, were overexpressed in S. cerevisiae to determine how unsaturated fatty acids affect cellular stress tolerance of cells. After cloning and plasmid recombination, the recombinant S. cerevisiae cells were constructed. Analysis of membrane fatty acid contents revealed that the recombinant S. cerevisiae with overexpression of OLE1 and FAD2 genes contained higher levels of fatty acids C16:1 (2.77 times), C18:1 (1.51 times) and C18:2 (4.15 times) than the wild-type S. cerevisiae pY15TEF1. In addition, recombinant S. cerevisiae cells were more resistant to multiple stresses, and exhibited improved membrane functionality, including membrane fluidity and integrity. CONCLUSION: These findings demonstrated that strengthening the expression of desaturases was beneficial to stress tolerance. Overall, this study may provide a suitable means to build a cell factory of industrial yeast cells with high tolerance during biological manufacturing. © 2023 Society of Chemical Industry.
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Ácidos Graxos Dessaturases , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos/metabolismoRESUMO
Microfibril-associated glycoprotein-1 (MAGP1), a crucial extracellular matrix protein, contributes to the initiation and progression of different cancers. However, the role of MAGP1 in laryngeal cancer is not clear. The purpose of this study was to investigate the clinical significance and biological function of MAGP1 in laryngeal cancer. MAGP1 was upregulated in public databases and laryngeal cancer tissues, and high MAGP1 expression led to a poor prognosis and was identified as an independent prognostic marker. Knocking-down MAGP1 inhibited laryngeal cancer cell growth and metastasis. According to gene set enrichment analysis, high MAGP1 expression revealed enrichment in Wnt/ß-catenin signaling and knocking-down MAGP1 in laryngeal cancer cells also caused degradation, de-activation, re-location and loss of stability of ß-catenin. Additionally, we observed MAGP1 in laryngeal cancer cells inhibits angiogenesis in an MMP7-dependent way. In conclusion, our study suggests a clinical role of MAGP1 in laryngeal cancer, signifying its potential as a therapeutic target in the future.
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Neoplasias Laríngeas , beta Catenina , Humanos , Angiogênese/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Via de Sinalização WntRESUMO
Reperfusion after ischemia would cause massive myocardial injury, which leads to oxidative stress (OS). Calcium homeostasis imbalance plays an essential role in myocardial OS injury. CaV1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CSL54-64. In this study, the effect of Ahf-caltide, derived from CSL54-64, on myocardial OS injury was investigated. Ahf-caltide decreased the levels of LDH, MDA and ROS and increased heart rate, coronary flow, cell survival and SOD activity during OS. In addition, Ahf-caltide permeated into H9c2 cells and increased CaV1.2, CaVß2 and CAST levels by inhibiting protein degradation. At different Ca2+ concentrations (25 nM, 10 µM, 1 mM), the binding of CSL to the IQ motif in the C terminus of the CaV1.2 channel was increased in a H2O2 concentration-dependent manner. CSL54-64 was predicted to be responsible for the binding of CSL to CaV1.2. In conclusion, Ahf-caltide exerted a cardioprotective effect on myocardial OS injury by stabilizing CaV1.2 protein expression. Our study, for the first time, proposed that restoring calcium homeostasis by targeting the CaV1.2 calcium channel and its regulating factor CAST could be a novel treatment for myocardial OS injury.
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Cálcio , Peróxido de Hidrogênio , Cálcio/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Miócitos Cardíacos/metabolismo , Peptídeos/farmacologia , Estresse OxidativoRESUMO
Acute lung injury (ALI) is a progressive inflammatory injury, and mesenchymal stem cells (MSCs) can be used to treat ALI. MSC-conditioned medium (MSC-CM) contains many cytokines, in which keratinocyte growth factor (KGF) is a soluble factor that plays a role in lung development. We aim to explore the protective effects of MSCs secreted KGF on ALI, and investigate the involvement of epithelial sodium channel (ENaC), which are important in alveolar fluid reabsorption. Both lipopolysaccharides (LPS)-induced mouse and alveolar organoid ALI models were established to confirm the potential therapeutic effect of MSCs secreted KGF. Meanwhile, the expression and regulation of ENaC were determined in alveolar type II epithelial (ATII) cells. The results demonstrated that MSC-CM and KGF could alleviate the extent of inflammation-related pulmonary edema in ALI mice, which was abrogated by a KGF neutralizing antibody. In an alveolar organoid ALI model, KGF in MSC-CM could improve the proliferation and decrease the differentiation of ATII cells. At the cellular level, the LPS-inhibited protein expression of ENaC could be reversed by KGF in MSC-CM. In addition, bioinformatics analysis and our experimental data provided the evidence that the NF-κB signaling pathway may be involved in the regulation of ENaC. Our research confirmed that the therapeutic effect of MSC-CM on edematous ALI was closely related to KGF, which may be involved in the proliferation and differentiation of ATII cells, as well as the upregulation of ENaC expression by the inhibition of NF-κB signaling pathway.
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Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Canais Epiteliais de Sódio/metabolismo , NF-kappa B/metabolismo , Fator 7 de Crescimento de Fibroblastos/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Células-Tronco Mesenquimais/metabolismo , PulmãoRESUMO
Heart failure has become a public health problem that we cannot avoid choosing to face in today's context. In the case of heart failure, pathological cardiac hypertrophy plays a major role because of its condition of absolute increase in ventricular mass under various stresses. Ferroptosis, it could be defined as regulatory mechanisms that regulate cell death in the absence of apoptosis in iron-dependent cells. This paper introduces various new research findings on the use of different regulatory mechanisms of cellular ferroptosis for the treatment of heart failure and cardiac hypertrophy, providing new therapeutic targets and research directions for clinical treatment. The role and mechanism of ferroptosis in the field of heart failure has been increasingly demonstrated, and the relationship between cardiac hypertrophy, which is one of the causes of heart failure, is also an area of research that we should focus on. In addition, the latest applications and progress of inducers and inhibitors of ferroptosis are reported in this paper, updating the breakthroughs in their fields.
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Ferroptose , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Apoptose , Morte Celular , CardiomegaliaRESUMO
Pathological myocardial hypertrophy initially develops as an adaptive response to cardiac stress, which can be induced by many diseases. It is accompanied by adverse cardiovascular events, including heart failure, arrhythmias, and death. The purpose of this research was to explore the molecular mechanism of a novel peptide Athycaltide-1 (ATH-1) in the treatment of Ang II-induced pathological myocardial hypertrophy. In this study, the mRNA of Control group, Ang II group, ATH-1 group and Losartan group mice were sequenced by high-throughput sequencing technology. The results showed that the differentially expressed genes (DEGs) were significantly enriched in cell response to oxidative stress, regulation of reactive oxygen species metabolism and calmodulin binding. Then, the oxidation level of mouse hearts and H9c2 cardiomyocytes in each group and the expression of key proteins of CaMKII/HDAC/MEF2C and ERK1/2 signaling pathways were detected to preliminarily verify the positive effect of ATH-1. At the same time, the effect of ATH-1 was further determined by adding reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) and CaMKII inhibitor AIP in vitro. The results showed that ATH-1 could significantly reduce the level of oxidative stress in hypertrophic cardiomyocytes and inhibiting the activation of CaMKII and ERK1/2.
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Sistema de Sinalização das MAP Quinases , Animais , Camundongos , Angiotensina II/efeitos adversos , Angiotensina II/metabolismo , Angiotensina II/toxicidade , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Células Cultivadas , Miócitos Cardíacos , Peptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Zygosaccharomyces rouxii has excellent fermentation performance and good tolerance to osmotic stress. Acetyl-CoA is a crucial intermediate precursor in the central carbon metabolic pathway of yeast. This study investigated the effect of engineering acetyl-CoA metabolism on the membrane functionality and stress tolerance of yeast. Firstly, exogenous supplementation of acetyl-CoA improved the biomass and the ability of unsaturated fatty acid synthesis of Z. rouxii under salt stress. Q-PCR results suggested that the gene ACSS (coding acetyl-CoA synthetase) was significantly up-expressed. Subsequently, the gene ACSS from Z. rouxii was transformed and heterologously expressed in S. cerevisiae. The recombinant cells exhibited better multiple stress (salt, acid, heat, and cold) tolerance, higher fatty acid contents, membrane integrity, and fluidity. Our findings may provide a suitable means to enhance the stress tolerance and fermentation efficiency of yeast under harsh fermentation environments.
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Saccharomyces cerevisiae , Zygosaccharomyces , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Acetilcoenzima A/metabolismo , Acetilcoenzima A/farmacologia , Zygosaccharomyces/genética , FermentaçãoRESUMO
Herein, a facile method is proposed for the bulk synthesis of conductive non-metallic carbon nanospheres with controllable morphology to replace conventional metal calibration reference materials (CRMs), such as gold nanoparticles and copper grids. The prepared nanospheres had an average diameter of â¼222 ± 23 nm, where silicon dioxide formed the core and the shell was comprised of the carbon layer. The structure of the conductive carbon nanospheres was characterized using FTIR, SEM, EDS and TEM. Additionally, an innovative design was demonstrated by 3D printing the calibration carrier device. Furthermore, the stability and image linear distortion of the conductive carbon nanospheres were verified using analysis of variance (ANOVA). The results demonstrated that the accelerating voltage, magnification, and various positions in the X/Y axes had no significant effect on measured diameter of nanospheres, which was evident from all the p values being greater than 0.05. The comprehensive set of results reveal that conductive carbon nanospheres have great potential to replace traditional CRMs.