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In this work, the Mn, Co, Ce co-doped corn cob biochar (MCCBC) as catalytic particle electrodes in a three-dimensional heterogeneous electro-Fenton-like (3D-HEFL) system for the efficient degradation of coking wastewater was investigated. Various characterization methods such as SEM, EDS, XRD, XPS and electrochemical analysis were employed for the prepared materials. The results showed that the MCCBC particle electrodes had excellent electrochemical degradation performances of COD in coking wastewater, and the COD removal and degradation rates of the 3D/HEFL system were 85.35% and 0.0563 min-1 respectively. RSM optimized conditions revealed higher COD removal rate at 89.23% after 31.6 min of electrolysis. The efficient degradability and wide adaptability of the 3D/HEFL system were due to its beneficial coupling mechanism, including the synergistic effect between the system factors (3D and HEFL) as well as the synergistic interactions between the ROS (dominated by â¢OH and supplemented by O2â¢-) in the system. Moreover, the COD removal rate of MCCBC could still remain at 81.41% after 5 cycles with a lower ion leaching and a specific energy consumption of 11.28 kWh kg-1 COD. The superior performance of MCCBC, as catalytic particle electrodes showed a great potential for engineering applications for the advanced treatment of coking wastewater.
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Carvão Vegetal , Cocaína , Coque , Poluentes Químicos da Água , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Coque/análise , Oxirredução , Eletrodos , Cocaína/análise , Poluentes Químicos da Água/análiseRESUMO
The effect of obesity on wound-related outcomes in post-ovarian cancer patients is not clear. A number of studies on the association of fat with post-operation injury in ovarian carcinoma have produced contradictory findings. This study aims to conduct a study of the available data to assess the association of obese individuals with significant surgery results in ovarian cancer. We looked up Cochrane Library, Embase, and PubMed for qualifying research on ovarian cancer operations to determine the primary evidence for evaluating the association of obesity with post-surgical wound injury in ovarian cancer. The odds ratio (OR) was analysed with a fixed effect model if the variability of the study was small; otherwise, the analysis of the data was done with a random effect model. Out of 1259 related trials which were reviewed for eligibility, 6 publications were chosen from 2009 to 2019, 3076 patients who had had an operation for ovarian cancer. Obesity has been linked to an increased rate of wound-related complications in ovarian cancer operations compared to those without obesity (OR, 0.50; 95% CI, 0.37, 0.69 p < 0.0001). Non-obesity was significantly less likely to occur with respect to operation time compared to those with obesity (MD, -48.00; 95% CI, -55.33, -40.68 p < 0.00001). There were no statistically significant differences in the rate of haemorrhage after the operation (OR, 0.26; 95% CI, 0.04, 1.57, p = 0.14). Because of the limited number of trials in this meta-analysis, caution should be exercised in their treatment. More high-quality research with a large sample is required in order to confirm the findings.
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Neoplasias Ovarianas , Ferida Cirúrgica , Humanos , Feminino , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Ferida Cirúrgica/complicações , Obesidade/complicações , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E_2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E_2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.
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Medicamentos de Ervas Chinesas , Metabolômica , Insuficiência Ovariana Primária , Animais , Feminino , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Humanos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Modelos Animais de DoençasRESUMO
Non-small cell lung cancer (NSCLC) is a major global health threat with high incidence and mortality. Modulator of apoptosis-1 (MOAP1), also named MAP-1, belongs to the PNMA gene family and plays a key role in regulating apoptosis and tumor growth. However, its influences on NSCLC are largely unclear, and thus were explored in our present study, particularly the underlying mechanisms. Here, we initially find that MOAP1 expression is significantly decreased in NSCLC patients compared with the normal ones, and negatively correlated with the TNM and pathologic stages among patients. Additionally, MOAP1 low expression predicts a poorer prognosis than that of the NSCLC patients expressing higher MOAP1. Our in vitro studies confirm much lower MOAP1 expression in NSCLC cell lines. Of note, promoting MOAP1 expression strongly reduces the proliferation and induces apoptosis in NSCLC cells, accompanied with cell cycle arrest distributed in G0/G1 phase. Moreover, we find that MOAP1 has a negative correlation with Th2 cells' infiltration, but a positive correlation with the infiltration levels of eosinophils. Epithelial mesenchymal transition (EMT) process is also greatly restrained in NSCLC cells with MOAP1 over-expression, as proved by the reduced migration and invasion of cells. We further identify a positive correlation between MOAP1 and tripartite motif-containing 68 (TRIM68) in patients with NSCLC. Further analysis shows that TRIM68 directly interacts with MOAP1 and stabilizes MOAP1. Importantly, TRIM68 can activate MOAP1 by inducing the K63-linked polyubiquitination of MOAP1. Finally, animal studies verify that promoting MOAP1 efficiently suppresses tumor growth and lung metastasis in the nude mice. Collectively, our results reveal a novel mechanism through which MOAP1 stabilized by TRIM68 inhibits NSCLC development and targeting MOAP1 for its up-regulation may be a promising therapeutic strategy for NSCLC treatment.
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Proteínas Reguladoras de Apoptose , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteínas com Motivo Tripartido , Animais , Camundongos , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Camundongos Nus , Humanos , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas com Motivo Tripartido/metabolismoRESUMO
A new palladium-catalyzed reductive double carbonylation of nitroarenes with aryl halides for the synthesis of benzoxazin-4-ones has been reported. The key to success was the use of Mo(CO)6 as a reductant and bench-stable solid carbonyl sources. Various aryl iodides, bromides, and trifluoromethanesulfonates are suitable reaction partners and produce corresponding benzoxazin-4-one derivatives in moderate to good yields. Preliminary mechanistic studies indicate that nitrosoarene was first generated as the key intermediate through nitro reduction. Remarkably, this method avoids the use of toxic CO gas and is further applied to the late-stage modification of estrone.
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Paládio , Substâncias Redutoras , Catálise , Estrutura Molecular , Compostos OrgânicosRESUMO
BACKGROUND: Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), whether anomalous NVC would be present is unclear. PURPOSE: To investigate NVC changes and potential neural basis in MELAS by combining resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL). STUDY TYPE: Prospective. SUBJECTS: Twenty-four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up. FIELD STRENGTH/SEQUENCE: 3.0 T, resting-state gradient-recalled echo-planar imaging and pseudo-continuous 3D ASL sequences. ASSESSMENT: Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS. Regional NVC was also evaluated by voxel-wise and lesion-wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS. STATISTICAL TESTS: Two-sample t-test, paired-sample t-test, Gaussian random fields correction. A P value <0.05 was considered statistically significant. RESULTS: Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke-like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage. DATA CONCLUSIONS: This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.
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A photoactive metal-organic framework (MOF), [K(H2O)][Cu(DPNDI)][Cu(DPNDI)(CH3CN)(H2O)] [Cu1.5(DPNDI)1.5H1.5P2W18O62]·2H2O (Cu(Ι)W-DPNDI), was prepared by combining a functional photosensitizer N, N'-bis(4-pyridylmethyl)naphthalene diimide (DPNDI), copper(I) ions, and an oxidation catalyst [P2W18O62]6- into a single framework via a hydrothermal process. Cu(Ι)W-DPNDI exhibited a stable structure, strong light absorption capacity, a suitable band gap, and photoelectric properties, which provided favorable conditions for photocatalysis. In the confined space, the well-aligned Cu(I) ions and POM polyanions played a synergetic effect in the electron-transfer process and reactive oxygen species generation. By coupling photocatalysis and heterogeneous Fenton-like catalysis, Cu(Ι)W-DPNDI displayed high efficiency for the selective oxidation of aromatic alcohols, with up to >99% selectivity and 75% yield.
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A novel pyridine-modified chitosan (PYCS) adsorbent was prepared in a multistep procedure including the successive grafting of 2-(chloromethyl) pyridine hydrochloride and crosslinking with glutaraldehyde. Then, the as-prepared materials were used as adsorbents for the removal of metal ions from acidic wastewater. Batch adsorption experiments were carried out to study the impact of various factors such as solution pH value, contact time, temperature, and Fe (III) concentration. The results showed that the absorbent exhibited a high capacity of Fe (III) and the maximum adsorption capacity was up to 66.20 mg/g under optimal experimental conditions (the adsorption time = 12 h, pH = 2.5, and T = 303 K). Adsorption kinetics and isotherm data were accurately described by the pseudo-second-order kinetic model and Sips model, respectively. Thermodynamic studies confirmed that the adsorption was a spontaneous endothermic process. Moreover, the adsorption mechanism was investigated using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results revealed the pyridine group forms a stable chelate with iron (III) ions. Therefore, this acid-resistant adsorbent exhibited excellent adsorption performance for heavy metal ions from acidic wastewater compared to the conventional adsorbents, helping realize direct decontamination and secondary utilization.
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In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.
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Insuficiência Ovariana Primária , Feminino , Humanos , Camundongos , Animais , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente , Proteômica , Transdução de Sinais , Glicosídeos/efeitos adversosRESUMO
OBJECTIVES: To develop an MRI-based multi-lesion radiomics model for discrimination of relapsing-remitting multiple sclerosis (RRMS) and its mimicker neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: A total of 112 patients with RRMS (n = 63) or NPSLE (n = 49) were assigned to training and test sets with a ratio of 3:1. All lesions across the whole brain were manually segmented on T2-weighted fluid-attenuated inversion recovery images. For each single lesion, 371 radiomics features were extracted and trained using machine learning algorithms, producing Radiomics Index for Lesion (RIL) for each lesion and a single-lesion radiomics model. Then, for each subject, single lesions were assigned to one of two disease courts based on their distance to decision threshold, and a Radiomics Index for Subject (RIS) was calculated as the mean RIL value of lesions on the higher-weighted court. Accordingly, a subject-level discrimination model was constructed and compared with performances of two radiologists. RESULTS: The subject-based discrimination model satisfactorily differentiated RRMS and NPSLE in both training (AUC = 0.967, accuracy = 0.892, sensitivity = 0.917, and specificity = 0.872) and test sets (AUC = 0.962, accuracy = 0.931, sensitivity = 1.000, and specificity = 0.875), significantly better than the single-lesion radiomics method (training: p < 0.001; test: p = 0.001) Besides, the discrimination model significantly outperformed the senior radiologist in the training set (training: p = 0.018; test: p = 0.077) and the junior radiologist in both the training and test sets (training: p = 0.008; test: p = 0.023). CONCLUSIONS: The multi-lesion radiomics model could effectively discriminate between RRMS and NPSLE, providing a supplementary tool for accurate differential diagnosis of the two diseases. KEY POINTS: ⢠Radiomic features of brain lesions in RRMS and NPSLE were different. ⢠The multi-lesion radiomics model constructed using a merging strategy was comprehensively superior to the single-lesion-based model for discrimination of RRMS and NPSLE. ⢠The RRMS-NPSLE discrimination model showed a significantly better performance or a trend toward significance than the radiologists.
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Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologiaRESUMO
A redox-active metal-organic framework, Cu(I)-TPT, was synthesized by combination of Cu(I), the halogenoid cyanide group (CN), and redox-active organic bridging ligand 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT) into one single framework. Cu(I)-TPT displays a two-dimensional (2D) plane structure by 1D -Cu(I)-CN- chains connected with TPT ligands. Cu(I)-TPT exhibits intrinsic semiconductive features with a moderate bandgap energy (1.97 eV). Under irradiation, Cu(I)-TPT has an electrical conductivity of 2 × 10-7 S cm-1 in the presence of the sacrificial electron donor ethanol under the ambient test conditions, which is owing to the π-π stacking interactions between TPT moieties, the d-π conjugation between the Cu(I) ion and the CN ligands, and the permanent microporosity. Cu(I)-TPT displayed highly efficient hole-electron separation and ordered electron transfer, which is beneficial for the photoreduction of nitrobenzene. In addition, Cu(I)-TPT displays high efficiency in carboxylic cyclization of alkynol with CO2 because it possesses highly decentralized Cu(I) catalytic sites to the active C≡C bond of alkynol and affluent N atoms on the 2D sheets to facilitate the trapping and activation of CO2.
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The secondary metabolite pseudopyronine B, isolated from Pseudomonas mosselii P33, was biotransformed by human P450 enzymes, heterologously expressed in the fission yeast Schizosaccharomyces pombe. Small-scale studies confirmed that both CYP4F2 and CYP4F3A were capable of oxidizing the substrate, with the former achieving a higher yield. In larger-scale studies using CYP4F2, three new oxidation products were obtained, the structures of which were elucidated by UV-vis, 1D and 2D NMR, and HR-MS spectroscopy. These corresponded to hydroxylated, carboxylated, and ester derivatives (1-3) of pseudopyronine B, all of which had been oxidized exclusively at the ω-position of the C-6 alkyl chain. In silico homology modeling experiments highlighted key interactions between oxygen atoms of the pyrone ring and two serine residues and a histidine residue of CYP4F2, which hold the substrate in a suitable orientation for oxidation at the terminus of the C-6 alkyl chain. Additional modeling studies with all three pseudopyronines revealed that the seven-carbon alkyl chain of pseudopyronine B was the perfect length for oxidation, with the terminal carbon lying close to the heme iron. The antibacterial activity of the substrates and three oxidation products was also assessed, revealing that oxidation at the ω-position removes all antimicrobial activity. This study both increases the range of known substrates for human CYF4F2 and CYP4F3A enzymes and demonstrates their utility in producing additional natural product derivatives.
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Antibacterianos , Sistema Enzimático do Citocromo P-450 , Pironas , Humanos , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Biotransformação , Sistema Enzimático do Citocromo P-450/metabolismo , Família 4 do Citocromo P450/metabolismo , Hidroxilação , Oxirredução , Pironas/química , Pironas/metabolismo , Pironas/farmacologia , Schizosaccharomyces/enzimologiaRESUMO
Cardiolipin is a mitochondrial signature phospholipid that plays a pivotal role in maintaining cardiac health. A loss of tetralinoleoyl cardiolipin (TLCL), the predominant cardiolipin species in the healthy mammalian heart, is implicated in the pathogenesis of coronary heart disease (CHD) through poorly defined mechanisms. Here, we identified acyl-coenzyme A:lysocardiolipin acyltransferase-1 (ALCAT1) as the missing link between hypoxia and CHD in an animal model of myocardial infarction (MI). ALCAT1 is an acyltransferase that promotes mitochondrial dysfunction in aging-related diseases by catalyzing pathological remodeling of cardiolipin. In support of a causative role of ALCAT1 in CHD, we showed that ALCAT1 expression was potently upregulated by MI, linking myocardial hypoxia to oxidative stress, TLCL depletion, and mitochondrial dysfunction. Accordingly, ablation of the ALCAT1 gene or pharmacological inhibition of the ALCAT1 enzyme by Dafaglitapin (Dafa), a potent and highly specific ALCAT1 inhibitor, not only restored TLCL levels but also mitochondrial respiration by attenuating signal transduction pathways mediated by hypoxia-inducible factor 1α (HIF-1α). Consequently, ablation or pharmacological inhibition of ALCAT1 by Dafa effectively mitigated CHD and its underlying pathogenesis, including dilated cardiomyopathy, left ventricle dysfunction, myocardial inflammation, fibrosis, and apoptosis. Together, the findings have provided the first proof-of-concept studies for targeting ALCAT1 as an effective treatment for CHD.
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Cardiolipinas , Doença da Artéria Coronariana , Animais , Cardiolipinas/metabolismo , Doença da Artéria Coronariana/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Mamíferos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Estresse OxidativoRESUMO
OBJECTIVES: To examine the wear occurring in a group of new Gracey curettes due to the sharpening and scaling processes and record the number of service cycles before breakage. METHODS: This study included 592 working ends of Gracey curettes that were subjected to cycles of sharpening and scaling. Three-dimensional measurements of the blades and the status of the working ends were recorded before and after each process. RESULTS: With an increase in the number of usage cycles, the three-dimensional measurements of the blades decreased. During this study, 184 working ends were broken, of which 38.59% were of #11/12 Gracey curettes, and only 8.15% were of #7/8 Gracey curettes. The average number of cycles required for the fracture of Gracey curettes was 14.34. Cox regression analyses showed that the factors influencing the survival cycles were the tip width before usage and the type of Gracey curette. Moreover, the sharpening process was responsible for approximately half of the total instrument wear. Among the four types of Gracey curettes, the #11/12 Gracey curettes showed the greatest amount of sharpening wear, accounting for >50% of the total wear. CONCLUSIONS: The service life of Gracey curettes varies according to their types; the #11/12 Gracey curettes are more susceptible to breakage, while #7/8 Gracey curettes tend to have a long service life. Furthermore, the sharpening process was responsible for a considerable amount of curette wear.
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Raspagem Dentária , Humanos , Microscopia Eletrônica de VarreduraRESUMO
Human brain atlases are essential for research and surgical treatment of Parkinson's disease (PD). For example, deep brain stimulation for PD often requires human brain atlases for brain structure identification. However, few atlases can provide disease-specific subcortical structures for PD, and most of them are based on T1w and T2w images. In this work, we construct a HybraPD atlas using fused quantitative susceptibility mapping (QSM) and T1w images from 87 patients with PD. The constructed HybraPD atlas provides a series of templates, that is, T1w, GRE magnitude, QSM, R2*, and brain tissue probabilistic maps. Then, we manually delineate a parcellation map with 12 bilateral subcortical nuclei, which are highly related to PD pathology, such as sub-regions in globus pallidus and substantia nigra. Furthermore, we build a whole-brain parcellation map by combining existing cortical parcellation and white-matter segmentation with the proposed subcortical nuclei map. Considering the multimodality of the HybraPD atlas, the segmentation accuracy of each nucleus is evaluated using T1w and QSM templates, respectively. The results show that the HybraPD atlas provides more accurate segmentation than existing atlases. Moreover, we analyze the metabolic difference in subcortical nuclei between PD patients and healthy control subjects by applying the HybraPD atlas to calculate uptake values of contrast agents on positron emission tomography (PET) images. The atlas-based analysis generates accurate disease-related brain nuclei segmentation on PET images. The newly developed HybraPD atlas could serve as an efficient template to study brain pathological alterations in subcortical regions for PD research.
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Gânglios da Base/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Núcleo Subtalâmico/diagnóstico por imagem , Núcleos Talâmicos/diagnóstico por imagem , Adulto , Idoso , Atlas como Assunto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodosRESUMO
m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.
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BACKGROUND: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the dynamic functional connectivity (dFC) of brain networks in MELAS has not been explored. PURPOSE: To investigate the abnormalities of dFC in patients with MELAS at the acute and chronic stages, and to determine the possible relations between dynamic connectivity alterations and volumes of stroke-like lesions (SLLs). STUDY TYPE: Prospective. SUBJECTS: Twenty-two MELAS patients at the acute stage, 23 MELAS patients at the chronic stage, and 22 healthy controls. FIELD STRENGTH/SEQUENCE: Single-shot gradient-recalled echo planar imaging (EPI) sequence at 3T. ASSESSMENT: Dynamic FC states were estimated using the sliding window approach and k-means clustering analyses. Combined with graph theory, the topological properties of the dFC network were also accessed. STATISTICAL TESTS: Permutation test, Pearson correlation coefficient, and false discovery rate correction. RESULTS: We identified four dFC states and found that MELAS patients (especially at the acute stage) spent more time in a state with weaker connectivity (state 1) and less time in states with stronger connectivity. In addition, volumes of acute SLLs were positively correlated with mean dwell time in state 1 (r = 0.539, P < 0.05) and negatively correlated with the number of transitions (r = -0.520, P < 0.05). Furthermore, MELAS patients at the acute stage exhibited significantly increased global efficiency (P < 0.01) and decreased local efficiency (P < 0.001) compared to the controls and the patients at the chronic stage. Patients at the chronic stage only showed significantly (P < 0.001) decreased local efficiency compared to the controls. DATA CONCLUSION: Our findings suggest similar and distinct dFC alterations in MELAS patents at the acute and chronic stages, providing novel insights for understanding the neuropathological mechanisms of MELAS. Level of Evidence 2 Technical Efficacy Stage Stage 2 J. MAGN. RESON. IMAGING 2021;53:427-436.
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Acidose Láctica , Síndrome MELAS , Acidente Vascular Cerebral , Encéfalo/diagnóstico por imagem , Humanos , Síndrome MELAS/diagnóstico por imagem , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
BACKGROUND: Swallow tail sign (STS) on MRI is presumed to be an imaging biomarker of nigrosome-1, which may exhibit a similar role as positron emission tomography (PET), indicating dopaminergic degeneration. PURPOSE: To investigate whether an alteration of STS could serve as an alternative screening sign compared with PET in the diagnosis of early-stage Parkinson's disease (esPD). STUDY TYPE: Prospective. POPULATION: Thirty-seven patients with esPD and 27 age- and sex-matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: Quantitative susceptibility mapping images were collected on 3T MRI and [18 F]9-fluoropropyl-(+)-dihydrotetra-benazine PET images were acquired using a 64 rings PET/CT scanner. ASSESSMENT: Alterations of STS and striatal uptake in each hemisphere were visually rated on a 0-2 points scale. Point 2: normal appearance of STS/normal striatal uptake; Point 1: partial loss of STS/uptake reduction confined to the putamen; Point 0: total loss of STS/uptake reduction extended to the caudate nucleus. The concordance rate of STS rating and ipsilateral striatal binding was calculated at the nuclei level. At the participant level, an evaluation rating was calculated by adding the STS ratings from both hemispheres to distinguish esPD from HCs. STATISTICAL TESTS: The intra- and interobserver agreement were tested using Cohen's kappa and the intraclass correlation coefficient. Hotelling's T-squared test was used to compare the difference of rating points. Receiver operating characteristic analysis was performed to evaluate the diagnostic power. RESULTS: The intra- and interobserver agreement for STS and striatal uptake rating was over 0.75. There was no significant difference of rating point distribution (P = 0.084). The concordance rate was 94.3% for the right side and 91.4% for the left. Using bilateral partial loss of STS as the threshold, the achieved sensitivity and specificity for discriminating esPD from HCs were 94.59% and 92.49%, respectively. DATA CONCLUSION: STS alterations corresponded well with striatal uptake on PET in esPD, and our proposed evaluation scale of STS had satisfactory diagnostic performance in discriminating the disease. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
Assuntos
Doença de Parkinson , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos ProspectivosRESUMO
BACKGROUND: Loss of swallow tail sign (STS) on iron-sensitive magnetic resonance imaging (MRI) has been recognized as an imaging feature in parkinsonism (PS). PURPOSE: To investigate the diagnostic and differential diagnostic value of STS scale on susceptibility map-weighted imaging (SMWI) in PS, including Parkinson's disease (PD), progressive supranuclear palsy syndrome (PSP), and multiple system atrophy (MSA), and to evaluate its correlation with disease severity. MATERIAL AND METHODS: Ninety-nine patients (55 PD, 29 PSP, and 15 MSA) and 47 healthy controls (HC) were prospectively recruited and scanned using quantitative susceptibility mapping (QSM). STS was visually assessed on SMWI derived from QSM. STS scale in the range of 0-4 at participant level was calculated by summing bilateral STS scores (0-2). We used receiver operating characteristic analysis of STS scale for evaluating the diagnostic power of parkinsonism and Spearman's correlation for assessing disease severity. RESULTS: Frequency distribution of STS scale was significantly different in parkinsonism and HC groups, and among PD, PSP, and MSA subgroups. STS scale ≤3 could distinguish parkinsonism from HC with high accuracy (91.78%), PD from HC (91.18%), and MSA from HC (88.71%). STS scale ≤2 could distinguish PSP from HC (96.05%). STS scale = 0 could distinguish PSP from PD (70.24%) and PSP from MSA (72.73%). STS scale was negatively correlated with H-Y stage (P = 0.007, r = -0.359) and duration of disease (P = 0.006, r = -0.367) in PD patients. CONCLUSION: STS scale on SMWI may serve as a useful imaging biomarker for diagnosis of parkinsonism and disease progression evaluation in PD.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
The study aims to investigate the effect of the compatibility of paeonol and paeoniflorin(hereinafter referred to as the compatibility) on the expression of myocardial proteins in rats with myocardial ischemia injury and explore the underlying mechanism of the compatibility against myocardial ischemia injury. First, the acute myocardial infarction rat model was established by ligation of the anterior descending branch of the left coronary artery. The model rats were given(ig) paeonol and paeoniflorin. Then protein samples were collected from rat cardiac tissue and quantified by tandem mass tags(TMT) to explore the differential proteins after drug intervention. The experimental results showed that differential proteins mainly involved phagocytosis engulfment, extracellular space, and antigen binding, as well as Kyoto encyclopedia of genes and genomes(KEGG) pathways of complement and coagulation cascades, syste-mic lupus erythematosus, and ribosome. In this study, the target proteins and related signaling pathways identified by differential proteomics may be the biological basis of the compatibility against myocardial ischemia injury in rats.