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BACKGROUND: The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches. METHODS: Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated. RESULTS: A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3. CONCLUSIONS: PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.
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Neoplasias da Mama , Limoninas , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Dietilestilbestrol , Genisteína , Simulação de Acoplamento Molecular , Prognóstico , RNA MensageiroRESUMO
Because of the pathological indication and the physiological functions, bile acids (BAs) have occupied the research hotspot in recent decades. Although extensive efforts have been paid onto BAs sub-metabolome characterization, as the subfamily, BA glucuronides (gluA-BAs) profile is seldom concerned. Here, we made efforts to develop a LC-MS/MS program enabling quantitative gluA-BAs sub-metabolome characterization and to explore the differential species in serum between intrahepatic cholestasis of pregnancy (ICP) patients and healthy subjects. To gain as many authentic gluA-BAs as possible, liver microsomes from humans, rats, and mice were deployed to conjugate glucuronyl group to authentic BAs through in vitro incubation. Eighty gluA-BAs were captured and subsequently served as authentic compounds to correlate MS/MS spectral behaviors to structural features using squared energy-resolved MS program. Optimal collision energy (OCE) of [M-H]->[M-H-176.1]- was jointly administrated by [M-H]- mass and glucuronidation site, and identical exciting energies corresponding to 50% survival rate of 1st-generation fragment ion (EE50) were observed merely when the aglycone of a gluA-BA was consistent with the suspected structure. Through integrating high-resolution m/z, OCE, and EE50 information to identify gluA-BAs in a BAs pool, 97 ones were found and identified, and further, quantitative program was built for all annotated gluA-BAs by assigning OCEs to [M-H]->[M-H-176.1]- ion transitions. Quantitative gluA-BAs sub-metabolome of ICP was different from that of the healthy group. More GCDCA-3-G, GDCA-3-G, TCDCA-7-G, TDCA-3-G, and T-ß-MCA-3-G were distributed in the ICP group. Above all, this study not only offered a promising analytical tool for in-depth gluA-BAs sub-metabolome characterization, but also clarified gluA-BAs allowing the differentiation of ICP and healthy subjects.
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High-performance sodium-ion batteries (SIBs) require anode materials with high capacity and fast kinetics. Based on first-principles calculations, we propose BC3N2 and BC3N2/graphene (B/G) heterostructure as potential SIB anode materials. The BC3N2 monolayer exhibits intrinsic metallic behavior. In addition, BC3N2 possesses a low Na+ diffusion barrier (0.15 eV), a high storage capacity (777 mA h g-1), a low open-circuit voltage (0.72 V), and a tiny axial expansion (0.36%). Compared with the BC3N2 monolayer, the B/G heterostructure exhibits a lower diffusion barrier of 0.027 eV, suggesting a much faster diffusion. More importantly, although the B/G heterostructure possesses heavier molar weight, its theoretical capacity (689 mA h g-1) is comparable to that of the BC3N2 monolayer. Based on the above-mentioned properties, we hope both the BC3N2 monolayer and the B/G heterostructure would be promising anodes for SIBs.
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OBJECTIVES: To investigate the prevalence and associated factors of health anxiety (HA) in patients with Temporomandibular Disorders (TMDs) using the 8-item Whiteley Index (WI-8) scale. MATERIALS AND METHODS: Three hundred and twenty-nine TMDs patients completed the Visual Analog Scale (VAS), WI-8, Jaw Functional Limitation Scale-8 (JFLS-8), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) scales. Clinical examinations were conducted following the Diagnostic Criteria for TMDs Axis I. RESULTS: The prevalence of HA among TMDs patients was 18.54%. Patients with HA had higher scores of VAS-current (p = 0.026), VAS-maximum (p = 0.024), VAS-average (p = 0.030), JFLS-8 (p < 0.001), GAD-7 (p < 0.001) and PHQ-9 (p < 0.001), lower maximum mouth opening (p = 0.016), lower proportion of structure-related TMDs (p = 0.028), and higher proportion of pain-related TMDs (p < 0.001) compared to those without HA. The correlation coefficient was 0.61 (p < 0.001) between WI-8 and GAD-7 and 0.64 (p < 0.001) between WI-8 and PHQ-9. CONCLUSION: Approximately one-fifth of patients with TMDs experienced HA. HA was associated with pain perception, functional limitations, depressive, and anxiety symptoms in individuals with TMDs. HA may contribute to heightened subjective pain experiences rather than structural changes in the TMJ.
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BACKGROUND: Temporomandibular joint disorders (TMDs) are common in young adults, and the link between chronotype profile and TMDs is unclear. OBJECTIVE: This study examined TMD prevalence and chronotype distribution and explored the relationship between chronotype and TMDs in young adults. MATERIALS AND METHODS: A total of 663 students from Sichuan University completed questionnaires. Chronotype profiles were assessed using the Morningness-Eveningness Questionnaire, and TMDs were screened using the Fonseca Memory Index. To validate the findings, 68 TMD patients and 136 controls were enrolled. RESULTS: The prevalence of TMDs was 69.7%, with significant differences among chronotype profiles. The intermediate profile was the most common chronotype. Eveningness profile was associated with higher TMDs prevalence and severity. Muscle pain and side movement difficulty scores were higher in eveningness and intermediate profiles. Female gender (OR 2.345; 95% CI 1.668-3.297) was a TMD risk factor, while morningness profile (OR 0.537; 95% CI 0.297-0.970) was protective. Validation with TMD patients and controls supported these findings, showing higher eveningness profile prevalence in the TMD groups. CONCLUSIONS: TMDs have a high prevalence in college students, chronotype profiles shown to be associated with TMDs. Morningness is the protection factor in TMDs and PT, eveningness is a risk factor for IT.
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OBJECTIVES: This study aimed to provide visualized knowledge maps to show the evolving trends and key focal points of Class III malocclusion research through a comprehensive bibliometric analysis. MATERIALS AND METHODS: Class III malocclusion research published between 2000 and 2023 was retrieved from the Web of Science Core Collection. VOSviewer was utilized to count the citation and publication number of authors, institutions, countries and journals. Co-occurrence, co-citation, and cluster analyses and burst detection were conducted using CiteSpace. RESULTS: A total of 3,682 publications on Class III malocclusion were included in the bibliometric analysis. During 2000-2023, both the annual publication count and citation frequency exhibited a gradual upward trajectory, with a noticeable surge in recent years. In terms of production and citation counts of Class III malocclusion research, the core journal is the American Journal of Orthodontics and Dentofacial Orthopedics. Furthermore, apart from the primary keyword 'Class III malocclusion', 'orthognathic surgery' was identified as keyword with the most frequency. The cluster analysis of cited references reveals that the research focal points have shifted to 'skeletal anchorage' and 'surgery-first approach'. Furthermore, the burst detection identified 'quality of life' as a potential research hotspot since it has recently gained increasing scholarly attention. CONCLUSIONS: The current study provides scholars with the knowledge maps of evolving trends and prominent topics of Class III malocclusion research and a summary of research progress on various priorities during different periods. These findings are expected to provide a valuable guidance to facilitate the future research on Class III malocclusion.
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Bibliometria , Má Oclusão Classe III de Angle , Humanos , Pesquisa em OdontologiaRESUMO
OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.
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Dor Facial , Medição da Dor , Transtornos da Articulação Temporomandibular , Humanos , Transtornos da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/psicologia , Feminino , Masculino , Adulto , Dor Facial/fisiopatologia , Pessoa de Meia-Idade , Adolescente , Limiar da Dor/fisiologiaRESUMO
The electroencephalogram (EEG) has recently emerged as a pivotal tool in brain imaging analysis, playing a crucial role in accurately interpreting brain functions and states. To address the problem that the presence of ocular artifacts in the EEG signals of patients with obstructive sleep apnea syndrome (OSAS) severely affects the accuracy of sleep staging recognition, we propose a method that integrates a support vector machine (SVM) with genetic algorithm (GA)-optimized variational mode decomposition (VMD) and second-order blind identification (SOBI) for the removal of ocular artifacts from single-channel EEG signals. The SVM is utilized to identify artifact-contaminated segments within preprocessed single-channel EEG signals. Subsequently, these signals are decomposed into variational modal components across different frequency bands using the GA-optimized VMD algorithm. These components undergo further decomposition via the SOBI algorithm, followed by the computation of their approximate entropy. An approximate entropy threshold is set to identify and remove components laden with ocular artifacts. Finally, the signal is reconstructed using the inverse SOBI and VMD algorithms. To validate the efficacy of our proposed method, we conducted experiments utilizing both simulated data and real OSAS sleep EEG data. The experimental results demonstrate that our algorithm not only effectively mitigates the presence of ocular artifacts but also minimizes EEG signal distortion, thereby enhancing the precision of sleep staging recognition based on the EEG signals of OSAS patients.
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Artefatos , Apneia Obstrutiva do Sono , Humanos , Máquina de Vetores de Suporte , Processamento de Sinais Assistido por Computador , Eletroencefalografia/métodos , AlgoritmosRESUMO
Aiming at the problem that existing emotion recognition methods fail to make full use of the information in the time, frequency, and spatial domains in the EEG signals, which leads to the low accuracy of EEG emotion classification, this paper proposes a multi-feature, multi-frequency band-based cross-scale attention convolutional model (CATM). The model is mainly composed of a cross-scale attention module, a frequency-space attention module, a feature transition module, a temporal feature extraction module, and a depth classification module. First, the cross-scale attentional convolution module extracts spatial features at different scales for the preprocessed EEG signals; then, the frequency-space attention module assigns higher weights to important channels and spatial locations; next, the temporal feature extraction module extracts temporal features of the EEG signals; and, finally, the depth classification module categorizes the EEG signals into emotions. We evaluated the proposed method on the DEAP dataset with accuracies of 99.70% and 99.74% in the valence and arousal binary classification experiments, respectively; the accuracy in the valence-arousal four-classification experiment was 97.27%. In addition, considering the application of fewer channels, we also conducted 5-channel experiments, and the binary classification accuracies of valence and arousal were 97.96% and 98.11%, respectively. The valence-arousal four-classification accuracy was 92.86%. The experimental results show that the method proposed in this paper exhibits better results compared to other recent methods, and also achieves better results in few-channel experiments.
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Eletroencefalografia , Emoções , Eletroencefalografia/métodos , Humanos , Emoções/fisiologia , Processamento de Sinais Assistido por Computador , Atenção/fisiologia , Algoritmos , Redes Neurais de Computação , Nível de Alerta/fisiologiaRESUMO
BACKGROUND: Poor reporting quality and spin in randomized controlled trial (RCT) abstracts can lead to misinterpretation and distorted interpretation of results. OBJECTIVES: This methodological study aimed to assess the reporting quality and spin among RCT abstracts on splint therapy for temporomandibular disorders (TMD) and explore the association between spin and potentially related factors. METHODS: The authors searched PubMed for RCTs on splint therapy for TMD. The reporting quality of each abstract was assessed using the original 16-item CONSORT for abstracts checklist. The authors evaluated the presence and characteristics of spin only in abstracts with nonsignificant primary outcomes according to pre-determined spin strategies. Logistic regression analyses were performed to identify factors associated with the presence of spin. RESULTS: A total of 148 abstracts were included in the reporting quality evaluation. The mean overall CONSORT score (OCS) was 5.86 (score range: 0-16). Only interventions, objectives and conclusions were adequately reported. Of the 61 RCT abstracts included for spin analysis, spin was identified in 38 abstracts (62.3%), among which 32 abstracts (52.3%) had spin in the Results section and 21 (34.4%) had spin in the Conclusions section. A significantly lower presence of spin was found in studies with exact p-value reporting (OR: 0.170; 95% CI: 0.032-0.887; p = .036) and a two-arm comparison design (OR: 11.777; 95% CI: 2.171-63.877; p = .004). CONCLUSIONS: The reporting quality of RCT abstracts on splint therapy for TMD is suboptimal and the prevalence of spin is high. More awareness and joint efforts are needed to improve reporting quality and minimize spin.
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BACKGROUND: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. OBJECTIVE: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. METHODS: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non-EDS group (score < 10). The Jaw Functional Limitation Scale 8-item (JFLS-8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire 9-item (PHQ-9). All included patients were diagnosed with pain-related TMD (PT), intra-articular TMD (IT) or combined TMD (CT). RESULTS: Compared with non-EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ-9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD-7 score (B = 0.73) were significantly associated with an increased score on the JFLS-8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007). CONCLUSION: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.
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Transtornos do Sono-Vigília , Transtornos da Articulação Temporomandibular , Masculino , Humanos , Feminino , Medição da Dor , Ansiedade , Dor , Transtornos da Articulação Temporomandibular/complicaçõesRESUMO
OBJECTIVE: The objective of the study was to investigate the relationship between types of disc displacement (DD) diagnosed by magnetic resonance imaging (MRI), and the risk (presence or absence) and severity of condylar erosion (CE) graded using cone-beam computed tomography (CBCT) in adult Temporomandibular disorders (TMD) patients. METHODS: A total of 353 TMD patients (283 females, 70 males) underwent MRI scans to categorise DD as normal (NA), anterior displacement with reduction (ADDR), or anterior displacement without reduction (ADDNR). CE severity was graded on a scale of 0-3 (absence, mild, moderate or severe) using CBCT. To establish the plausibility and cut-off points for CE diagnosis, the severity of CE was then further divided into three classifications: Grade 0 versus 1 + 2 + 3; Grades 0 + 1 versus 2 + 3; Grades 0 + 1 + 2 versus 3. Logistic regression analysis was performed, adjusting for age, gender and joint correlation. RESULTS: ADDNR significantly increased the risk of CE compared with NA (OR = 10.04, 95% CI: [6.41, 15.73]) and showed a significant increase in CE severity across all classifications (ORs = 10.04-18.95). The effects of ADDNR were significant in both genders (p < .001) and had a greater impact in females. ADDR was predominantly associated with mild CE. CONCLUSIONS: ADDNR significantly increased the risk and severity of CE independent of gender when compared to NA, whereas ADDR was mainly associated with mild CE. Slight cortical discontinuity may represent a subclinical diagnosis requiring further investigation.
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Tomografia Computadorizada de Feixe Cônico , Luxações Articulares , Imageamento por Ressonância Magnética , Côndilo Mandibular , Disco da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Masculino , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/patologia , Adulto , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/patologia , Disco da Articulação Temporomandibular/diagnóstico por imagem , Disco da Articulação Temporomandibular/patologia , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/patologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem , Fatores de RiscoRESUMO
Land subsidence induced by coal mining (MLS) has posed a huge threat to the ecological environment, buildings, roads, and other infrastructure safety in mining areas. However, the prediction and evaluation of MLS is relatively complex, and the reliability of the prediction results is closely related to factors such as the professional knowledge and engineering experience of researchers. This paper aims to combine intelligent optimization algorithms: ant lion optimizer (ALO), bald eagle search (BES), bird swarm algorithm (BSA), harris hawks optimization (HHO), and sparrow search algorithm (SSA), with machine learning model of gradient boosting with categorical features support algorithm (CatBoost) to predict MLS. To achieve this goal, five hybrid models based CatBoost were developed and the prediction accuracy and reliability of the models were compared and analyzed. The prediction performance of the hybrid models has been significantly improved on the basis of a single model, of which the SSA-CatBoost model has the most obvious improvement (from R2 = 0.927 to 0.965, RMSE = 0.541 to 0.377, MAE = 0.386 to 0.297, VAF = 92.720 to 95.837). The importance and predictive contribution of all input features to predictive labels were studied with the Shapley method. The research results indicate that hybrid model technology is a reliable MLS prediction method. This study can help mining technicians use machine learning methods to study the degree of MLS damage to the surface environment and provide scientific advanced prediction and evaluation for the protection and management of the ecological environment in mining areas and the formulation of safety production measures.
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Algoritmos , Engenharia , Reprodutibilidade dos Testes , Meio Ambiente , ConhecimentoRESUMO
BACKGROUND: In the classification of bruxism patients based on electroencephalogram (EEG), feature extraction is essential. The method of using multi-channel EEG fusing electrocardiogram (ECG) and Electromyography (EMG) signal features has been proved to have good performance in bruxism classification, but the classification performance based on single channel EEG signal is still understudied. We investigate the efficacy of single EEG channel in bruxism classification. METHODS: We have extracted time-domain, frequency-domain, and nonlinear features from single EEG channel to classify bruxism. Five common bipolar EEG recordings from 2 bruxism patients and 4 healthy controls during REM sleep were analyzed. The time domain (mean, standard deviation, root mean squared value), frequency domain (absolute, relative and ratios power spectral density (PSD)), and non-linear features (sample entropy) of different EEG frequency bands were analyzed from five EEG channels of each participant. Fine tree algorithm was trained and tested for classifying sleep bruxism with healthy controls using five-fold cross-validation. RESULTS: Our results demonstrate that the C4P4 EEG channel was most effective for classification of sleep bruxism that yielded 95.59% sensitivity, 98.44% specificity, 97.84% accuracy, and 94.20% positive predictive value (PPV). CONCLUSIONS: Our results illustrate the feasibility of sleep bruxism classification using single EEG channel and provides an experimental foundation for the development of a future portable automatic sleep bruxism detection system.
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Bruxismo do Sono , Fases do Sono , Humanos , Bruxismo do Sono/diagnóstico , Valor Preditivo dos Testes , Eletroencefalografia/métodos , AlgoritmosRESUMO
OBJECTIVE: The NLRP3 inflammasome mediates a range of inflammatory responses that are associated with an increasing number of pathological mechanisms. Over-activation of NLRP3 can exacerbate many diseases. However, NLRP3 antagonists have significant therapeutic potential. Moreover, NLRP3 plays an important role in limiting the growth and spread of some tumors, and NLRP3 agonists also have clinical value. MCC950 and BMS986299 are an antagonist and agonist of NLRP3, respectively. In light of the important clinical applications of NLRP3, especially for NLRP3 inhibitors, a computational method was used to investigate the interaction modes of MCC950 and BMS986299 with NLRP3 in order to design and develop more potent NLRP3 regulators. METHODS: In this study, the conformational behaviors of NLRP3 bound to the antagonist MCC950 in an inactive state and the agonist BMS986299 in an active state were investigated using 200 ns equilibrium all-atom molecular dynamics (MD) simulations, and then the analyses of the MD trajectories (RMSD, Rg, RMSF, SASA, PCA, and DCCM) were carried out to explore the mechanism of the antagonist and agonist on NLRP3 in the two different states. RESULTS: The RMSD, RMSF, Rg, SASA, and PCA analyses indicated that NLRP3 was more dispersive and less energetically stable in the active state than in the inactive state and that MCC950 significantly reduced the fluctuations of the interactive residues while BMS986299 did not. The antagonist MCC950 interacted with residues mainly in the NBD, HD1, WHD, and HD2 domains of NLRP3, whereas the agonist BMS986299 mainly in the NBD and WHD of NLRP3. Additionally, both compounds did not interact with residues located in the FISNA domain. The conformation of the FISNA domain appeared to change significantly when NLRP3 was translated from an inactive state to an active state. CONCLUSION: The antagonist may interact with residues mainly in the NBD, HD1, WHD, and HD2 domains, and the agonist may interact in the NBD and WHD domains. Our study provided new insights into the development of NLRP3 regulators.
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Aortic dissection (AD) is a severe vascular disease with high rates of mortality and morbidity. However, the underlying molecular mechanisms of AD remain unclear. Differentially expressed genes (DEGs) were screened by bioinformatics methods. Alterations of histopathology and inflammatory factor levels in ß-aminopropionitrile (BAPN)-induced AD mouse model were evaluated through Hematoxylin-Eosin (HE) staining and Enzyme-linked immunosorbent assay (ELISA), respectively. Reverse transcription quantitative real-time polymerase chain reaction was performed to detect DEGs expression. Furthermore, the role of LILRB4 in AD was investigated through Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry. Western blotting was employed to assess the phenotypic switch and extracellular matrix (ECM)-associated protein expressions in platelet-derived growth factor-BB (PDGF-BB)-stimulated in vitro model of AD. In the AD mouse model, distinct dissection formation was observed. TNF-α, IL-1ß, IL-8, and IL-6 levels were higher in the AD mouse model than in the controls. Six hub genes were identified, including LILRB4, TIMP1, CCR5, CCL7, MSR1, and CLEC4D, all of which were highly expressed. Further exploration revealed that LILRB4 knockdown inhibited the cell vitality and migration of PDGF-BB-induced HASMCs while promoting apoptosis and G0/G1 phase ratio. More importantly, LILRB4 knockdown promoted the protein expression of α-SMA and SM22α, while decreasing the expression of Co1, MMP2, and CTGF, which suggested that LILRB4 silencing promoted contractile phenotypic transition and ECM stability. LILRB4 knockdown inhibits the progression of AD. Our study provides a new potential target for the clinical treatment of AD.
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Dissecção Aórtica , Camundongos , Animais , Humanos , Becaplermina/metabolismo , Becaplermina/farmacologia , Regulação para Baixo , Miócitos de Músculo Liso/metabolismo , Apoptose , Proliferação de Células , Movimento Celular , Células Cultivadas , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismoRESUMO
OBJECTIVE: To investigate the effect of aerobic exercise intervention to inhibit cardiomyocyte apoptosis and thus improve cardiac function in myocardial infarction (MI) mice by regulating CTGF expression through miR-133a-3p. METHODS: Male C57/BL6 mice, 7-8 weeks old, were randomly divided into sham-operated group (S group), sham-operated +aerobic exercise group (SE group), myocardial infarction group (MI group) and MI + aerobic exercise group (ME group). The mice were anesthetized the day after training and cardiac function was assessed by cardiac echocardiography. Myocardial collagen volume fraction (CVF%) was analyzed by Masson staining. Myocardial CTGF, Bax and Bcl-2 were detected by Western blotting, and myocardial miR-133a-3p was measured by RT-qPCR. RESULTS: Compared with the S group, miR-133a-3p, Bcl-2 and EF were significantly decreased and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly increased in the MI group. Compared with the MI group, miR-133a-3p, Bcl-2 and EF were significantly increased, cardiac function was significantly improved, and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly decreased in ME group. The miR-133a-3p was significantly lower and CTGF was significantly higher in the H2O2 intervention group compared with the control group of H9C2 rat cardiomyocytes. miR-133a-3p was significantly higher and CTGF was significantly lower in the AICAR intervention group compared to the H2O2 intervention group. Compared with the control group of H9C2 rat cardiomyocytes, CTGF, Bax and Bax/Bcl-2 were significantly increased and Bcl-2 was significantly decreased in the miR-133a-3p inhibitor intervention group; CTGF, Bax and Bax/Bcl-2 were significantly decreased and Bcl-2 was significantly upregulated in the miR-133a-3p mimics intervention group. CONCLUSION: Aerobic exercise down-regulated CTGF expression in MI mouse myocardium through miR-133a-3p, thereby inhibiting cardiomyocyte apoptosis and improving cardiac function.
Assuntos
MicroRNAs , Infarto do Miocárdio , Ratos , Masculino , Camundongos , Animais , Caspase 3/metabolismo , Regulação para Baixo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Peróxido de Hidrogênio/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose/genéticaRESUMO
To address the issues of large imaging errors for small defects and the difficulty in depth evaluation using local wavenumber estimation for surface defect imaging, a novel three-dimensional (3D) evaluation method for surface defects using broadband laser-generated Rayleigh waves with wavenumber analysis is proposed. A finite element model is established to investigate the interaction between the Rayleigh wave and the surface defect and reveal the wavenumber change mechanism of the non-dispersive Rayleigh wave in the case of defects. It is discovered that when the Rayleigh wave encounters the surface defect, various mode-converted scattered waves are generated, resulting in the appearance of new components with wavenumbers lower than that of the incident Rayleigh wave in the wavenumber domain. Additionally, the maximum amplitude of the Rayleigh wave in the B-scan image increases as the defect depth increases. Based on the simulation analysis, a 3D evaluation method for surface defects is proposed. Firstly, the scattered Rayleigh wave caused by the defect is extracted using frequency-wavenumber analysis. Secondly, a space-frequency-wavenumber analysis is used to determine the local wavenumber of the scattered Rayleigh wave for defect imaging. Finally, the defect depth is estimated by analyzing the maximum amplitude of the Rayleigh wave. A surface defect detection experiment is conducted to verify the effectiveness of the proposed method, and the experimental results demonstrate that the proposed method can suppress noise interference and accomplish high-precision imaging of small surface defects compared to the traditional method. Moreover, the method can establish a linear mapping relationship between the defect depth and the maximum amplitude of the Rayleigh wave for depth evaluation. The research results can provide a potential application for the 3D evaluation of surface defects.