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This study aimed to develop Pickering emulsions for the encapsulation of Zanthoxylum bungeanum essential oil (ZBEO) using potato protein-chitosan composite nanoparticles (PCCNs). The sustained release properties of ZBEO, antifungal efficacy, and preservation effects of formulated ZBEO-Pickering emulsions (ZBEO-PEs) on mandarins were evaluated. Particle size, zeta potential, emulsifying activity (EAI), and emulsifying stability (ESI) analysis showed that PCCNs prepared with the potato protein to chitosan mass ratio of 10:3 provided optimal emulsification and stabilization. Techniques such as differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) demonstrated that chitosan introduction increased the wettability of potato protein through electrostatic, hydrogen bonding, and hydrophobic interactions. ZBEO-PEs formulated with 3.0 % PCCNs and an oil fraction of 0.40 showed best encapsulation efficiency, storage stability and sustained release. Confocal laser scanning microscopy confirmed the adsorption of PCCNs, forming dense interface layers on the surface of oil droplets, thereby enhancing the stability of ZBEO-PEs. In vitro experiments demonstrated enhanced antifungal activity of ZBEO-PEs against Penicillium italicum and Penicillium digitatum. Additionally, storage experiments indicated that ZBEO-PEs coatings effectively controlled postharvest decay caused by Penicillium spp. in mandarins. Overall, the findings suggest that PCCNs are highly efficient emulsifiers for ZBEO Pickering emulsions, underscoring their potential as preservative coatings for mandarins.
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OBJECTIVES: To construct and validate multiparametric MR-based radiomic models based on primary tumors for predicting lymph node metastasis (LNM) following neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) patients. METHODS: A total of 150 LARC patients from two independent centers were enrolled. The training cohort comprised 100 patients from center A. Fifty patients from center B were included in the external validation cohort. Radiomic features were extracted from the manually segmented volume of interests of the primary tumor before and after nCRT. Feature selection was performed using multivariate logistic regression analysis. The clinical risk factors were selected via the least absolute shrinkage and selection operator method. The radiologist's assessment of LNM was performed. Eight models were constructed using random forest classifiers, including four single-sequence models, three combined-sequence models, and a clinical model. The models' discriminative performance was assessed via receiver operating characteristic curve analysis quantified by the area under the curve (AUC). RESULTS: The AUCs of the radiologist's assessment, the clinical model, and the single-sequence models ranged from 0.556 to 0.756 in the external validation cohort. Among the single-sequence models, modelpost_DWI exhibited superior predictive power, with an AUC of 0.756 in the external validation set. In combined-sequence models, modelpre_T2_DWI_post had the best diagnostic performance in predicting LNM after nCRT, with a significantly higher AUC (0.831) than those of the clinical model, modelpre_T2_DWI, and the single-sequence models (all p < 0.05). CONCLUSIONS: A multiparametric model that incorporates MR radiomic features before and after nCRT is optimal for predicting LNM after nCRT in LARC. CRITICAL RELEVANCE STATEMENT: This study enrolled 150 LARC patients from two independent centers and constructed multiparametric MR-based radiomic models based on primary tumors for predicting LNM following nCRT, which aims to guide therapeutic decisions and predict prognosis for LARC patients. KEY POINTS: The biological characteristics of primary tumors and metastatic LNs are similar in rectal cancer. Radiomics features and clinical data before and after nCRT provide complementary tumor information. Preoperative prediction of LN status after nCRT contributes to clinical decision-making.
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In vegetable fermentation, pellicle is a common quality deterioration phenomenon. This study investigates the characteristics of glucose, organic acids, amino acids, and biogenic amines during the pellicle occurrence and disappearance of paocai. The results revealed a slight increase in pH of the fermentation system after pellicle occurred, and glucose was the main carbohydrate that microbial activity primary relied on. The microorganisms responsible for pellicle formation consumed organic acids in brine, but the lactic acid in paocai gradually increased and exceeded 25 mg/g. The appearance of pellicle caused a decrease in total free amino acids from 200.390 mg/100 g to 172.079 when pellicle occurred, whereas its impact on biogenic amines was not apparent. Through Kyoto Encyclopedia of Genes and Genomes pathway enrichment of metagenomics sequencing data, screening, and sorting of the key enzymes involved in organic acid metabolism, it was observed that the composition and species of the key microorganisms capable of metabolizing organic acids were more abundant before the appearance of pellicle. When pellicle occurred, lactic acid may be metabolized by Lactobacillus plantarum; in contrast, Lactobacillus and Pichia were associated with citric acid metabolism, and Lactobacillus, Pichia, Saccharomycodes, and Kazachstania were linked to malic acid metabolism. Moreover, Prevotella, Kazachstania, Lactobacillus, Vibrio, and Siphonobacter were implicated in succinic acid metabolism. Additionally, the production of tartaric acid and oxalic acid in paocai and brine resulted from abiotic effects. This knowledge offers a theoretical basis for precise control of paocai fermentation process. PRACTICAL APPLICATION: Our study revealed the specific situation of the metabolites produced by the microorganisms during the pollution and recovery process of pellicle in paocai fermentation, especially the effect of pellicle on the key process of organic acid metabolism. These research results provided theoretical basis for precise control of paocai fermentation.
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Aminoácidos , Fermentação , Ácido Láctico , Aminoácidos/metabolismo , Ácido Láctico/metabolismo , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética , Ácido Cítrico/metabolismo , Concentração de Íons de Hidrogênio , Aminas Biogênicas/metabolismo , Aminas Biogênicas/análise , Glucose/metabolismo , Malatos/metabolismo , Microbiologia de Alimentos , Alimentos Fermentados/microbiologia , Verduras/microbiologia , SaisRESUMO
Background: Glioblastoma (GBM) is a common and highly aggressive brain tumor with a poor prognosis for patients. It is urgently needed to identify potential small molecule drugs that specifically target key genes associated with GBM development and prognosis. Methods: Differentially expressed genes (DEGs) between GBM and normal tissues were obtained by data mining the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene function annotation was performed to investigate the potential functions of the DEGs. A protein-protein interaction (PPI) network was constructed to explore hub genes associated with GBM. Bioinformatics analysis was used to screen the potential therapeutic and prognostic genes. Finally, potential small molecule drugs were predicted using the DGIdb database and verified using chemical informatics methods including absorption, distribution, metabolism, excretion, toxicity (ADMET), and molecular docking studies. Results: A total of 429 DEGs were identified, of which 19 hub genes were obtained through PPI analysis. The hub genes were confirmed as potential therapeutic targets by functional enrichment and mRNA expression. Survival analysis and protein expression confirmed centromere protein A (CENPA) as a prognostic target in GBM. Four small molecule drugs were predicted for the treatment of GBM. Conclusion: Our study suggests some promising potential therapeutic targets and small molecule drugs for the treatment of GBM, providing new ideas for further research and targeted drug development.
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BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.
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Nervo Coclear , Surdez , Potenciais Evocados Auditivos do Tronco Encefálico , Humanos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Masculino , Feminino , Pré-Escolar , Nervo Coclear/fisiopatologia , Nervo Coclear/anormalidades , Surdez/fisiopatologia , Surdez/congênito , Surdez/cirurgia , Criança , Constrição Patológica , Implante Coclear/métodosRESUMO
PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.
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Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Criança , Humanos , Perda Auditiva Neurossensorial/cirurgia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Tronco Encefálico/cirurgia , Surdez/cirurgiaRESUMO
Caffeic acid transferase (COMT) is a key enzyme in the lignin and melatonin synthesis pathways and plays an important role in plant growth and development. All seed plants have two characteristics: they have vascular tissues, phloem, and xylem, and they can produce and reproduce seeds. In order to understand the distribution and evolution of COMTs in seed plants, we performed physicochemical property analysis, subcellular localization, phylogenetic analysis, conserved motif analysis, and protein interaction network analysis of 44 COMT homologs from 26 seed plants through in silico. The results showed that in seed plants, the structure of COMT genes tends to be stable in different plant taxa, while the relationship between the chromosomal positions of different COMT genes in the same plant was more intricate. The conserved distribution of COMT in seed plants reflected its highly specialized function.
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Ultrasound has been widely used for physical modifications of starch because of its effectiveness and environment friendliness; however, only a few reports have focused on the effect of varying ultrasonic treatments on the physicochemical properties of potato flour. In the present study, ultrasound at varying power levels (200, 300, 400, 500, and 600 W) and time intervals (20, 40, 60, 80, and 100 min) were used to obtain sonicated flour. Sonicated potato flour exhibited a significant (P < 0.05) decrease in blue value and oil holding capacity but an increase in swelling power, water solubility, syneresis rate, and transparency. Moreover, ultrasound decreased the RDS content while increasing RS and SDS contents. Thermal properties demonstrated significant (P < 0.05) increases in T0 (64.39â-83.52â) and TC (144.29â-146.87â) but a decrease in ΔH of the sonicated flour. SEM revealed wrinkles, less debris, and larger particle size at the surface of the sonicated flour. FTIR profiles of all samples exhibited similar characteristics peaks, but the sonicated flour had a higher R1047/1022 value. Additionally, ultrasound did not affect crystalline patterns, but it increased the crystallinity of the sonicated flour. Our study contributes to the understanding of physicochemical property changes of sonicated potato flour, which could have industrial applications.
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Farinha , Amido , Tamanho da PartículaRESUMO
Pellicle biofilm-forming bacteria Bacillus amyloliquefaciens are the major spoilage microorganisms of soy products. Due to their inherent resistance to antibiotics and disinfectants, pellicle biofilms formed are difficult to eliminate and represent a threat to food safety. Here, we assessed linalool's ability to prevent the pellicle of two spoilage B. amyloliquefaciens strains. The minimum biofilm inhibitory concentration (MBIC) of linalool against B. amyloliquefaciens DY1a and DY1b was 4 µL/mL and 8 µL/mL, respectively. The MBIC of linalool had a considerable eradication rate of 77.15% and 83.21% on the biofilm of the two strains, respectively. Scanning electron microscopy observations revealed that less wrinkly and thinner pellicle biofilms formed on a medium supplemented with 1/2 MBIC and 1/4 MBIC linalool. Also, linalool inhibited cell motility and the production of extracellular polysaccharides and proteins of the biofilm matrix. Furthermore, linalool exposure reduced the cell surface hydrophobicity, zeta potential, and cell auto-aggregation of B. amyloliquefaciens. Molecular docking analysis demonstrated that linalool interacted strongly with quorum-sensing ComP receptor and biofilm matrix assembly TasA through intermolecular hydrogen bonds, hydrophobic contacts, and van der Waals forces interacting with site residues. Overall, our findings suggest that linalool may be employed as a potential antibiofilm agent to control food spoilage B. amyloliquefaciens.
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Bacillus amyloliquefaciens , Simulação de Acoplamento Molecular , BiofilmesRESUMO
Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C-H activations, these arene functionalizations generally require directing groups to enable the C-H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C-H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C-H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C-H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C-H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations.
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Oxidantes , Paládio , Paládio/química , OxirreduçãoRESUMO
In this study, the quality indexes and sensory evaluation of Zanthoxylum armatum DC. from the main production areas in Southwest China were analyzed. Further, correlation analysis (CRA), principal component analysis (PCA) and cluster analysis (CA) were used to comprehensively evaluate the quality characteristics of Z. armatum. The results showed that the sensory indexes and physicochemical indexes of Z. armatum were significantly correlated. Five principal component factors were extracted from 12 indexes by PCA, and a comprehensive evaluation model of quality was established with Y = 0.2943Y1 + 0.2387Y2 + 0.1896Y3 + 0.1679Y4 + 0.1094Y5. On this basis, 21 producing areas were grouped into 4 groups and 3 groups by Q-type CA, respectively. R-type CA showed that the content of hydroxyl-sanshools, linalool content and b* value were the quality characteristic indexes of Z. armatum in Southwest China. This work provided an important theory and practice reference for Z. armatum quality evaluation and in-depth product development.
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Background: Previous studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis. Methods: 70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds. Results: 59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days. Conclusion: Our findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine.Clinical Trial Registration: http://www.chictr.org.cn/hvshowproject.aspx?id=11101, identifier ChiCTR-INR-17010559.
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OBJECTIVE: Particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) is a public health risk. We investigate PM2.5 on metabolites in cardiomyocytes and the influence of vitamin C on PM2.5 toxicity. MATERIALS AND METHODS: For 24 hours, H9C2 were exposed to various concentrations of PM2.5 (0, 100, 200, 400, 800 µg/ml), after which the levels of reactive oxygen species (ROS) and cell viability were measured using the cell counting kit-8 (CCK-8) and 2',7'-dichlorofluoresceindiacetate (DCFH2-DA), respectively. H9C2 were treated with PM2.5 (200 µg/ml) in the presence or absence of vitamin C (40 µmol/L). mRNA levels of interleukin 6(IL-6), caspase-3, fatty acid-binding protein 3 (FABP3), and hemeoxygenase-1 (HO-1) were investigated by quantitative reverse-transcription polymerase chain reaction. Non-targeted metabolomics by LC-MS/MS was applied to evaluate the metabolic profile in the cell. RESULTS: Results revealed a concentration-dependent reduction in cell viability, death, ROS, and increased expression of caspase-3, FABP3, and IL-6. In total, 15 metabolites exhibited significant differential expression (FC > 2, p < 0.05) between the control and PM2.5 group. In the PM2.5 group, lysophosphatidylcholines (LysoPC,3/3) were upregulated, whereas amino acids (5/5), amino acid analogues (3/3), and other acids and derivatives (4/4) were downregulated. PM2.5 toxicity was lessened by vitamin C. It reduced PM2.5-induced elevation of LysoPC (16:0), LysoPC (16:1), and LysoPC (18:1). DISCUSSION AND CONCLUSIONS: PM2.5 induces metabolic disorders in H9C2 cardiomyocytes that can be ameliorated by treatment with vitamin C.
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Pectin is a complex polysaccharide found in plant cell walls and interlayers. As a food component, pectin is benefit for regulating intestinal flora. Metabolites of intestinal flora, including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), are involved in blood glucose regulation. SCFAs promote insulin synthesis through the intestine-GPCRs-derived pathway and hepatic adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway to promote hepatic glycogen synthesis. On the one hand, BAs stimulate intestinal L cells and pancreatic α cells to secrete Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) through receptors G protein-coupled receptor (TGR5) and farnesoid X receptor (FXR). On the other hand, BAs promote hepatic glycogen synthesis through AMPK pathway. LPS inhibits the release of inflammatory cytokines through Toll-like receptors (TLRs)-myeloid differentiation factor 88 (MYD88) pathway and mitogen-activated protein kinase (MAPK) pathway, thereby alleviating insulin resistance (IR). In brief, both SCFAs and BAs promote GLP-1 secretion through different pathways, employing strategies of increasing glucose consumption and decreasing glucose production to maintain normal glucose levels. Notably, pectin can also directly inhibit the release of inflammatory cytokines through the -TLRs-MYD88 pathway. These data provide valuable information for further elucidating the relationship between pectin-intestinal flora-glucose metabolism.
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Hydroxyl-α-sanshool is the main alkylamide produced by Zanthoxylum armatum DC., and it is responsible for numbness after consuming Z. armatum-flavored dishes or food products. The present study deals with the isolation, enrichment, and purification of hydroxyl-α-sanshool. The results indicated that the powder of Z. armatum was extracted with 70% ethanol and then filtrated; the supernatant was concentrated to get pasty residue. Petroleum ether (60-90 °C) and ethyl acetate at a 3:2 ratio, with an Rf value of 0.23, were chosen as the eluent. Petroleum ether extract (PEE) and ethyl acetate-petroleum ether extract (E-PEE) were used as the suitable enriched method. Afterward, the PEE and E-PEE were loaded onto silica gel for silica gel column chromatography. Preliminary identification was carried out by TLC and UV. The fractions containing mainly hydroxyl-α-sanshool were pooled and dried by rotary evaporation. Lastly, all of the samples were determined by HPLC. The yield and recovery rates of hydroxyl-α-sanshool in the p-E-PEE were 12.42% and 121.65%, respectively, and the purity was 98.34%. Additionally, compared with E-PEE, the purity of hydroxyl-α-sanshool in the purification of E-PEE (p-E-PEE) increased by 88.30%. In summary, this study provides a simple, rapid, economical, and effective approach to the separation of high-purity hydroxyl-α-sanshool.
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Zanthoxylum , Zanthoxylum/química , Sílica Gel , Extratos Vegetais/química , CromatografiaRESUMO
This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.
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Implante Coclear , Implantes Cocleares , Auxiliares de Audição , Perda Auditiva Neurossensorial , Criança , Humanos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/terapia , Limiar Auditivo/fisiologiaRESUMO
OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising treatment option for migraines. This study aims to investigate the modulation effects of different taVNS frequencies along the central vagus nerve pathway in migraineurs. MATERIALS AND METHODS: Twenty-four migraineurs were recruited for a single-blind, crossover magnetic resonance imaging (MRI) study. The study consisted of two taVNS MRI scan sessions, in which either 1-Hz or 20-Hz taVNS was applied in a random order. Seed-based static and dynamic functional connectivity (FC) analyses were performed using two key nodes of the vagus nerve pathway, the nucleus tractus solitarius (NTS) and the locus coeruleus (LC). RESULTS: Static FC (sFC) analysis showed that 1) continuous 1-Hz taVNS resulted in an increase of NTS/LC-occipital cortex sFC and a decrease of NTS-thalamus sFC compared with the pre-1-Hz taVNS resting state, 2) continuous 20-Hz taVNS resulted in an increase of the LC-anterior cingulate cortex (ACC) sFC compared with the pre-20-Hz taVNS resting state, 3) 1-Hz taVNS produced a greater LC-precuneus and LC-inferior parietal cortex sFC than 20 Hz, and 4) 20-Hz taVNS increased LC-ACC and LC-super temporal gyrus/insula sFC in comparison with 1 Hz. Dynamic FC (dFC) analysis showed that compared with the pre-taVNS resting state, 1-Hz taVNS decreased NTS-postcentral gyrus dFC (less variability), 20-Hz taVNS decreased dFC of the LC-superior temporal gyrus and the LC-occipital cortex. Finally, a positive correlation was found between the subjects' number of migraine attacks in the past four weeks and the NTS-thalamus sFC during pre-taVNS resting state. CONCLUSIONS: 1-Hz and 20-Hz taVNS may modulate the sFC and dFC of key nodes in the central vagus nerve pathway differently. Our findings highlight the importance of stimulation parameters (frequencies) in taVNS treatment.
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Transtornos de Enxaqueca , Estimulação do Nervo Vago , Humanos , Imageamento por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/terapia , Método Simples-Cego , Nervo Vago/fisiologia , Estimulação do Nervo Vago/métodos , Estudos Cross-OverRESUMO
Osteosarcomas (OS) are highly metastatic and usually lead to poor outcomes. Epithelial-mesenchymal transition (EMT) is reported to be a critical event in metastasis. SIRT2 exerts dual functions in many different tumors. However, the underlying molecular mechanisms of SIRT2 in osteosarcoma cell metastasis and the question of whether SIRT2 regulates EMT have not been fully explored. In this study, we confirmed that SIRT2 was highly-expressed in human osteosarcoma MG63 and Saos-2 cell lines. The viability, migration and invasion of osteosarcoma cells were inhibited by knockdown of SIRT2 and were enhanced by overexpression of SIRT2. Moreover, SIRT2 positively regulated EMT and upregulated the protein levels of the mesenchymal markers N-cadherin and Vimentin and the levels of MMP2 and MMP9. A xenograft mouse model showed that SIRT2 knockdown in osteosarcoma cells led to reduced tumor growth, decreased expression of mesenchymal markers and impaired lung and liver metastasis in vivo. Furthermore, we showed that SIRT2 interacted with and upregulated the protein level of the EMT-associated transcription factor Snail. SIRT2 inhibited Snail degradation via its deacetylase activity. Knockdown of Snail abrogated the promoting effects of SIRT2 on migration and invasion of osteosarcoma cells. In conclusion, SIRT2 plays a crucial role in osteosarcoma metastasis by inhibiting Snail degradation and may serve as a novel therapeutic target to manage osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Camundongos , Animais , Sirtuína 2/genética , Sirtuína 2/metabolismo , Neoplasias Ósseas/patologia , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Invasividade Neoplásica/genética , Movimento Celular , Linhagem Celular Tumoral , Osteossarcoma/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Metástase NeoplásicaRESUMO
Background: Traditional epidemiological studies suggested that Neurodegenerative diseases (ND) might correlate with stroke. We intend to explore whether the two most common neurodegenerative diseases [Alzheimer's disease (AD) and Parkinson's disease (PD)] are causally associated with stroke and its subtypes. Methods: Two-sample Mendelian Randomization (MR) method was used to explore the causal relationships. Candidate genetic instrumental variables (IVs) for AD and PD were collected from the genome-wide association studies (GWAS) in European populations. The inverse-variance weighted (IVW) method was the primary method of MR analysis, and the weighted median method was supplementary. In addition, the MR-Egger method and the MR-PRESSO test were used as well. Results: We found no causal effects of AD on stroke, Ischemic stroke (IS), or Intracerebral hemorrhage (ICH). As for PD and stroke, our preliminary results showed PD could causally influence the risk of stroke [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.02-1.07; P = 0.001 by the IVW method], although the alternative method did not support this result. We identified the positive causal relationship between PD and the risk of IS (OR = 1.04; 95% CI: 1.02-1.07; P = 0.001 by the IVW method), and the alternative MR methods produced similar results. The present study found there was no causal relationship between PD and ICH. Conclusion: This study found a causal relationship between genetic susceptibility to PD and the incidence of stroke (especially IS) in the European population; however, there was no causal relation between AD and stroke risk.