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1.
Front Oncol ; 14: 1370393, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007099

RESUMO

Prolyl hydroxylase domain protein 2 (PHD2) is one of the intracellular oxygen sensors that mediates proteasomal degradation of hypoxia-inducible factor (HIF)-α via hydroxylation under normoxic conditions. Because of its canonical function in the hypoxia signaling pathway, PHD2 is generally regarded as a tumor suppressor. However, the effects of PHD2 in tumorigenesis are not entirely dependent on HIF-α. Based on analysis of data from the Cancer Genome Atlas (TCGA) database, we observed that the expression of PHD2 is upregulated in non-small cell lung cancer (NSCLC), which accounts for approximately 80-85% of lung cancers. This suggests that PHD2 may play an important role in NSCLC. However, the function of PHD2 in NSCLC remains largely unknown. In this study, we established PHD2-deficient H1299 cells and PHD2-knockdown A549 cells to investigate the function of PHD2 in NSCLC and found that PHD2 suppresses cell proliferation and metabolism but induces ROS levels in human NSCLC cells. Further results indicated that the function of PHD2 in NSCLC is dependent on its enzymatic activity and partially independent of HIF. Moreover, we performed RNA-sequencing and transcriptomic analysis to explore the underlying mechanisms and identified some potential targets and pathways regulated by PHD2, apart from the canonical HIF-mediated hypoxia signaling pathway. These results provide some clues to uncover novel roles of PHD2 in lung cancer progression.

2.
Brief Funct Genomics ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860675

RESUMO

In recent years, the application of single-cell transcriptomics and spatial transcriptomics analysis techniques has become increasingly widespread. Whether dealing with single-cell transcriptomic or spatial transcriptomic data, dimensionality reduction and clustering are indispensable. Both single-cell and spatial transcriptomic data are often high-dimensional, making the analysis and visualization of such data challenging. Through dimensionality reduction, it becomes possible to visualize the data in a lower-dimensional space, allowing for the observation of relationships and differences between cell subpopulations. Clustering enables the grouping of similar cells into the same cluster, aiding in the identification of distinct cell subpopulations and revealing cellular diversity, providing guidance for downstream analyses. In this review, we systematically summarized the most widely recognized algorithms employed for the dimensionality reduction and clustering analysis of single-cell transcriptomic and spatial transcriptomic data. This endeavor provides valuable insights and ideas that can contribute to the development of novel tools in this rapidly evolving field.

3.
J Contam Hydrol ; 265: 104381, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38851129

RESUMO

To study the pollutants immobilization and economy of biologically amended coastal soil, Alternanthera philoxeroides biomass (Bm), biochar (Bc), and dodecyldimethyl betaine (BS) modified Bc (BS-Bc) were used to amend coastal soil from Jialing, Fu, and Qu River. A runoff experiment was used to simulate the longitudinal migration and morphological changes of Pb(II) and chlortetracycline (CTC) in each amended coastal soil, and the economy of pollutants immobilization by different amended coastal soil were compared. The equilibrium time of Pb(II) and CTC in each amended coastal soil ranked in the order of BS-Bc-amended > Bc-amended > Bm-amended > unamended coastal soil. The average Pb(II) and CTC flow rate in different amended coastal soils presented an opposite trend with the equilibrium time. Pb(II) and CTC content all reduced with the increasing runoff length. Under the same soils, the content changes presented Bm and Bc amended > unamended > BS-Bc amended. CEC and clay content of coastal soils were the key factors affecting Pb(II) and CTC immobilization. The immobilization mechanisms were electrostatic attraction, ion exchange, surface precipitation, and complexation to Pb(II) and ion exchange and complexation to CTC. The economy of Pb(II) and CTC immobilization ranged from 0.5 to 9.0 and from 1.0 to 5.4 mg/¥, and coastal soil amended by BS-Bc had practical application value and high economy.

4.
Eur J Radiol ; 176: 111525, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38796885

RESUMO

OBJECTIVE: To investigate the value of quantitative contrast-enhanced ultrasonography (CEUS) in assessing and predicting early therapy response of non-Hodgkin's lymphoma (NHL). METHODS: Fifty-six cases of NHL were studied using CEUS before and after three cycles of R-CHOP / CHOP. Quantitative parameters such as arrival time (ATM), time to peak (TTP), △T = TTP-ATM, area under the gamma curve (Area), curve gradient (Grad), wash-out time (WT), base intensity (BI), peak intensity (PI) and ΔI = PI-BI were compared between the lymphoma and normal lymph nodes before and at mid-treatment, respectively. Changes in quantitative CEUS parameters were also compared between complete response (CR) and incomplete response(non-CR) groups. Besides, the correlation analysis was performed between pretreatment PI and changes in quantitative parameters. RESULTS: After three cycles of R-CHOP/CHOP, S/L (P < 0.001), PI (P = 0.002), ΔI (P < 0.001), Grad (P < 0.001), and Area (P < 0.001) of NHL were significantly decreased. The CR group and non-CR group only differed in ATM before treatment. In contrast, there was no statistical difference in any of the parameters between the two groups at mid-treatment. Finally, a significant correlation was observed between pre-treatment PI and PI△% (r = 0.736, P < 0.001). CONCLUSIONS: CEUS is promising for the assessment of response of NHL to R-CHOP/CHOP. Intra-lesion perfusion changes take precedence over morphological changes suggesting treatment efficacy. Pre-treatment ATM values may help to suggest efficacy outcomes and pre-treatment PI values may be a valid predictor of lymphoma perfusion response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Meios de Contraste , Ciclofosfamida , Doxorrubicina , Linfoma não Hodgkin , Ultrassonografia , Vincristina , Humanos , Masculino , Feminino , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ultrassonografia/métodos , Estudos de Casos e Controles , Adulto , Ciclofosfamida/uso terapêutico , Idoso , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Aumento da Imagem/métodos , Hexafluoreto de Enxofre , Reprodutibilidade dos Testes , Fosfolipídeos , Sensibilidade e Especificidade , Adulto Jovem
5.
Front Oncol ; 14: 1354288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800382

RESUMO

Objective: This study aims to combine ultrasound (US) elastography (USE) and radiomic to predict central cervical lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: A total of 204 patients with 204 thyroid nodules who were confirmed with PTMC and treated in our hospital were enrolled and randomly assigned to the training set (n = 142) and the validation set (n = 62). US features, USE (gender, shape, echogenic foci, thyroid imaging reporting and data system (TIRADS) category, and elasticity score), and radiomic signature were employed to build three models. A nomogram was plotted for the combined model, and decision curve analysis was applied for clinical use. Results: The combined model (USE and radiomic) showed optimal diagnostic performance in both training (AUC = 0.868) and validation sets (AUC = 0.857), outperforming other models. Conclusion: The combined model based on USE and radiomic showed a superior performance in the prediction of CLNM of patients with PTMC, covering the shortage of low specificity of conventional US in detecting CLNM.

6.
Nat Commun ; 15(1): 3533, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670937

RESUMO

Oxygen is essential for aerobic organisms, but little is known about its role in antiviral immunity. Here, we report that during responses to viral infection, hypoxic conditions repress antiviral-responsive genes independently of HIF signaling. EGLN1 is identified as a key mediator of the oxygen enhancement of antiviral innate immune responses. Under sufficient oxygen conditions, EGLN1 retains its prolyl hydroxylase activity to catalyze the hydroxylation of IRF3 at proline 10. This modification enhances IRF3 phosphorylation, dimerization and nuclear translocation, leading to subsequent IRF3 activation. Furthermore, mice and zebrafish with Egln1 deletion, treatment with the EGLN inhibitor FG4592, or mice carrying an Irf3 P10A mutation are more susceptible to viral infections. These findings not only reveal a direct link between oxygen and antiviral responses, but also provide insight into the mechanisms by which oxygen regulates innate immunity.


Assuntos
Prolina Dioxigenases do Fator Induzível por Hipóxia , Imunidade Inata , Fator Regulador 3 de Interferon , Oxigênio , Prolina , Peixe-Zebra , Animais , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Fator Regulador 3 de Interferon/metabolismo , Hidroxilação , Humanos , Prolina/metabolismo , Camundongos , Oxigênio/metabolismo , Células HEK293 , Fosforilação , Camundongos Knockout , Transdução de Sinais , Camundongos Endogâmicos C57BL
7.
Proc Natl Acad Sci U S A ; 121(17): e2314201121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38635631

RESUMO

To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of Sirt3 in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However, Sirt3 and Sirt5 double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of Sirt5 in Sirt3-deficient mice may counteract the increased viral susceptibility displayed in Sirt3-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.


Assuntos
Sirtuína 3 , Sirtuínas , Viroses , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Imunidade Inata , Lisina , Sirtuína 3/genética , Sirtuínas/genética , Peixe-Zebra , Proteínas de Peixe-Zebra
9.
Gene ; 893: 147935, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38381506

RESUMO

Hypoxia, an inadequate supply of tissue oxygen tension, has been reported to induce apoptosis of spermatogenic cells and is associated with male infertility. Neddylation, a post-translational modification similar to ubiquitination, has been shown to be involved in the hypoxia stress response. However, the functions of neddylation in hypoxia-induced apoptosis of spermatogenic cells and its association with male infertility remain largely unexplored. In this study, aiming to explore the role of neddylation in male infertility, we used the specific neddylation inhibitor MLN4924 for treatment in mouse type B spermatogonia GC-2 cells. Our results showed that MLN4924 had no apparent effect on GC-2 cell apoptosis under normoxia, but significantly increased apoptotic cells under hypoxia. Transcriptomic analysis and qPCR assay confirmed that MLN4924 could suppress the expression of hypoxia target genes in GC-2 cells under hypoxia. In addition, MLN4924 could enhance the induction of intracellular and mitochondrial reactive oxygen species (ROS) under hypoxia. These results indicate that the neddylation inhibitor MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells, and neddylation may play an important role in promoting spermatogenic cells to adapt to hypoxia stress.


Assuntos
Ciclopentanos , Infertilidade Masculina , Pirimidinas , Espermatogônias , Masculino , Animais , Camundongos , Humanos , Apoptose , Hipóxia
10.
Acta Radiol ; 65(5): 441-448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38232946

RESUMO

BACKGROUND: The overlapping nature of thyroid lesions visualized on ultrasound (US) images could result in misdiagnosis and missed diagnoses in clinical practice. PURPOSE: To compare the diagnostic effectiveness of US coupled with three mathematical models, namely logistic regression (Logistics), partial least-squares discriminant analysis (PLS-DA), and support vector machine (SVM), in discriminating between malignant and benign thyroid nodules. MATERIAL AND METHODS: A total of 588 thyroid nodules (287 benign and 301 malignant) were collected, among which 80% were utilized for constructing the mathematical models and the remaining 20% were used for internal validation. In addition, an external validation cohort comprising 160 nodules (80 benign and 80 malignant) was employed to validate the accuracy of these mathematical models. RESULTS: Our study demonstrated that all three models exhibited effective predictive capabilities for distinguishing between benign and malignant nodules, whose diagnostic effectiveness surpassed that of the TI-RADS classification, particularly in terms of true negative diagnoses. SVM achieved a higher diagnostic rate for malignant thyroid nodules (93.8%) compared to Logistics (91.5%) and PLS-DA (91.6%). PLS-DA exhibited higher diagnostic rates for benign thyroid nodules (91.9%) compared to Logistics (86.7%) and SVM (88.7%). Both the area under the receiver operating characteristic curve (AUC) values of PLS-DA (0.917) and SVM (0.913) were higher than that of Logistics (0.891). CONCLUSION: Our findings indicate that SVM had significantly higher rates of true positive diagnoses and PLS-DA exhibited significantly higher rates of true negative diagnoses. All three models outperformed the TI-RADS classification in discriminating between malignant and benign thyroid nodules.


Assuntos
Nódulo da Glândula Tireoide , Ultrassonografia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Ultrassonografia/métodos , Diagnóstico Diferencial , Adulto , Idoso , Máquina de Vetores de Suporte , Reprodutibilidade dos Testes , Modelos Teóricos , Sensibilidade e Especificidade , Glândula Tireoide/diagnóstico por imagem , Adulto Jovem , Adolescente , Análise dos Mínimos Quadrados , Estudos Retrospectivos , Análise Discriminante , Modelos Logísticos
11.
J Environ Manage ; 351: 119997, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160546

RESUMO

We report a novel modified semi-carbonized fiber (CF) prepared using cotton and acrylic clothes for derisking contaminated water to realize the resource utilization of discarded clothes in wastewater treatment. In this study, amphoteric and auxiliary modifiers were used to modify CFs for preparing amphoteric and amphoteric-auxiliary CFs. The basic physicochemical properties of different modified CFs were determined, and the microscopic morphology of modified CFs was detected. The isothermal adsorption characteristics of Cu(II) and Pb(II) on different modified CFs were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and material dose were compared. Physicochemical properties and microscopic morphology results proved that amphoteric and auxiliary modifiers were modified on the CF surface and changed the surface properties of CF. The adsorption capacities of Cu(II) and Pb(II) on modified CFs increased with the increase in equilibrium concentration of Cu(II) and Pb(II), and the isotherm was more suitable for Freundlich model fitting than that of the Langmuir model. The maximum adsorption capacities (qm) of Cu(II) and Pb(II) on different modified CFs were 60.72-81.26 mg/g and 102.58-161.72 mg/g, respectively, and presented the trend of amphoteric-auxiliary CFs > amphoteric CFs > CFs. Increasing pH and temperature and decreasing ionic strength and material dose were beneficial to Cu(II) and Pb(II) adsorption. The Cu(II) and Pb(II) adsorption process was a spontaneous, endothermic, and entropy-increasing reaction, and the adsorption rate was controlled by chemisorption. The adsorption amount of amphoteric-auxiliary CFs maintained about 65% of original materials after 3 times of regeneration. Electrostatic attraction, precipitation, complexation, and ion exchange were the main adsorption mechanisms. The cation exchange capacity and total pore volume of modified CFs were key to determining qm of Cu(II) and Pb(II).


Assuntos
Chumbo , Poluentes Químicos da Água , Temperatura , Cátions , Adsorção , Água , Vestuário , Poluentes Químicos da Água/química , Cinética , Concentração de Íons de Hidrogênio
12.
Cell Rep ; 43(1): 113606, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38127621

RESUMO

Activation of type I interferon (IFN-1) signaling is essential to protect host cells from viral infection. The full spectrum of IFN-I induction requires the activation of a number of cellular factors, including IκB kinase epsilon (IKKϵ). However, the regulation of IKKϵ activation in response to viral infection remains largely unknown. Here, we show that factor inhibiting hypoxia-inducible factor (HIF) (FIH), an asparaginyl hydroxylase, interacts with IKKϵ and catalyzes asparagine hydroxylation of IKKϵ at Asn-254, Asn-700, and Asn-701, resulting in the suppression of IKKϵ activation. FIH-mediated hydroxylation of IKKϵ prevents IKKϵ binding to TBK1 and TRAF3 and attenuates the cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex-catalyzed K63-linked polyubiquitination of IKKϵ at Lys-416. In addition, Fih-deficient mice and zebrafish are more resistant to viral infection. This work uncovers a previously unrecognized role of FIH in suppressing IKKϵ activation for IFN signaling and antiviral immune responses.


Assuntos
Quinase I-kappa B , Viroses , Animais , Camundongos , Quinase I-kappa B/metabolismo , Proteínas Repressoras/metabolismo , Sequência de Aminoácidos , Hidroxilação , Peixe-Zebra/metabolismo , Imunidade Inata
13.
Front Psychol ; 14: 1287891, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106401

RESUMO

Objective: This study aimed to evaluate the effects of self-help mindfulness-based cognitive therapy (MBCT-SH) on mindfulness, symptom change, and suicidal ideation in patients with depression. Methods: For this randomized controlled study, 97 patients were randomly assigned to either the MBCT-SH (n = 48) or control (n = 49) group. The Five Facet Mindfulness Questionnaire (FFMQ), Hamilton Depression Rating Scale (HAMD-24), and Suicide Attitude Questionnaire (SAQ) were used to assess mindfulness, depression symptoms, and suicidal ideation, respectively, at baseline (T0), intervention week 4 (T1), intervention week 8 (T2), and 3-month follow-up (T3). The groups were also compared on treatment costs and readmission rates at a 6-month follow-up. Results: In the MBCT-SH group, 46 of 48 participants (96%) completed the eight-week program. At T0, there were no statistically significant between-group differences in demographics, clinical characteristics, FFMQ, HAMD-24, or SAQ. Nor were there statistically significant differences on the HAMD-24 or SAQ between the MBCT-SH and control groups at T1 (p = 0.18 and p = 0.59, respectively), while mindfulness was significantly higher in the MBCT-SH group (t = 2.383, p = 0.019). At T2, there were significant between-group differences on the FFMQ, HAMD-24, and SAQ, all of which remained significant at T3. At the 6-month follow-up, per capita treatment costs were 5,298 RMB lower in the MBCT-SH group compared with the control group, while their readmission rates (6.1% and 4.2%, respectively) did not differ significantly. Conclusion: These findings support the feasibility and effectiveness of MBCT-SH among patients with depression. Clinical trial registration: http://www.chictr.org.cn, ChiCTR2300077850.

14.
J Biol Chem ; 299(12): 105420, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37923141

RESUMO

Prolyl hydroxylase domain (PHD)-containing enzyme 3 (PHD3) belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases. PHD3 catalyzes proline hydroxylation of hypoxia-inducible factor α (HIF-α) and promotes HIF-α proteasomal degradation through coordination with the pVHL complex under normoxic conditions. However, the relationship between PHD3 and the hypoxic response is not well understood. In this study, we used quantitative real-time PCR assay and O-dianisidine staining to characterize the hypoxic response in zebrafish deficient in phd3. We found that the hypoxia-responsive genes are upregulated and the number of erythrocytes was increased in phd3-null zebrafish compared with their wild-type siblings. On the other hand, we show overexpression of phd3 suppresses HIF-transcriptional activation. In addition, we demonstrate phd3 promotes polyubiquitination of zebrafish hif-1/2α proteins, leading to their proteasomal degradation. Finally, we found that compared with wild-type zebrafish, phd3-null zebrafish are more resistant to hypoxia treatment. Therefore, we conclude phd3 has a role in hypoxia tolerance. These results highlight the importance of modulation of the hypoxia signaling pathway by phd3 in hypoxia adaptation.


Assuntos
Prolina Dioxigenases do Fator Induzível por Hipóxia , Oxigênio , Pró-Colágeno-Prolina Dioxigenase , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Prolina/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Deleção de Genes , Oxigênio/metabolismo
15.
Acta Biochim Pol ; 70(3): 609-614, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37672760

RESUMO

Vitamin D deficiency (VDD) causes a wide range of health problems, including anemia in infants. If not treated promptly, it may create serious issues for infants with long-term impacts. Therefore, a satisfactory solution to this problem is required. This investigation was to explore the correlation between the blood 25-hydroxyvitamin D (25(OH)D) levels and childhood anemia. In this investigation, a cross-sectional examination was performed on 2,942 babies ranging in age from 2 to 36 months and classified into three cohorts: VDD (Vitamin D deficiency), VDI (Vitamin D insufficiency), and VDS (Vitamin D sufficiency). Multiple-variables and multinomially-related logistic regressions for examining the anemia status-vitamin D (Vit-D) relationship of the baseline as the interpretable visual quality models were examined. The median serum 25(OH)D level in 2,942 infants was 24.72±4.26 ng/l, with 661 cases (22.5%) of VDD and 1710 cases of deficiency (58.1%), and a noticeable seasonal variation (p<0.05). Anemia was present in 28.5% of the VDD group compared with 3.3% in vit-D sufficient infants (p<0.0001). Lower levels of 25(OH)D were found to be associated with an increased risk of anemia in a multiple-variable regression analysis. In healthy children, low 25(OH)D levels were associated with increased risk of anemia. Biologically inspired, primary care physicians should assess Vit-D levels and place a greater emphasis on adequate supplementation for deficiency prevention.


Assuntos
Anemia , Deficiência de Vitamina D , Lactente , Criança , Humanos , Pré-Escolar , Fenômenos Biomecânicos , Biônica , Estudos Transversais , Vitamina D , Vitaminas , Deficiência de Vitamina D/diagnóstico , Anemia/diagnóstico
16.
Sci Rep ; 13(1): 16047, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749121

RESUMO

This study compared the diagnostic efficiency of benign and malignant breast nodules using ultrasonographic characteristics coupled with several machine-learning models, including logistic regression (Logistics), partial least squares discriminant analysis (PLS-DA), linear support vector machine (Linear SVM), linear discriminant analysis (LDA), K-nearest neighbor (KNN), artificial neural network (ANN) and random forest (RF). The clinical information and ultrasonographic characteristics of 926 female patients undergoing breast nodule surgery were collected and their relationships were analyzed using Pearson's correlation. The stepwise regression method was used for variable selection and the Monte Carlo cross-validation method was used to randomly divide these nodule cases into training and prediction sets. Our results showed that six independent variables could be used for building models, including age, background echotexture, shape, calcification, resistance index, and axillary lymph node. In the prediction set, Linear SVM had the highest diagnosis rate of benign nodules (0.881), and Logistics, ANN and LDA had the highest diagnosis rate of malignant nodules (0.910~0.912). The area under the ROC curve (AUC) of Linear SVM was the highest (0.890), followed by ANN (0.883), LDA (0.880), Logistics (0.878), RF (0.874), PLS-DA (0.866), and KNN (0.855), all of which were better than that of individual variances. On the whole, the diagnostic efficacy of Linear SVM was better than other methods.


Assuntos
Calcificação Fisiológica , Calcinose , Feminino , Humanos , Área Sob a Curva , Análise por Conglomerados , Modelos Teóricos
17.
J Biol Chem ; 299(8): 105074, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37481210

RESUMO

SIRT7 is a member of the sirtuin family proteins with nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase activity, which can inhibit the activity of hypoxia-inducible factors independently of its enzymatic activity. However, the role of SIRT7 in affecting hypoxia signaling in vivo is still elusive. Here, we find that sirt7-null zebrafish are more resistant to hypoxic conditions, along with an increase of hypoxia-responsive gene expression and erythrocyte numbers, compared with their wildtype siblings. Overexpression of sirt7 suppresses the expression of hypoxia-responsive genes. Further assays indicate that sirt7 interacts with zebrafish hif-1αa, hif-1αb, hif-2αa, and hif-2αb to inhibit their transcriptional activity and mediate their protein degradation. In addition, sirt7 not only binds to the hypoxia responsive element of hypoxia-inducible gene promoters but also causes a reduction of H3K18Ac on these promoters. Sirt7 may regulate hypoxia-responsive gene expression through its enzymatic and nonenzymatic activities. This study provides novel insights into sirt7 function and sheds new light on the regulation of hypoxia signaling by sirt7.


Assuntos
Oxigênio , Sirtuínas , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteólise , Sirtuínas/genética , Sirtuínas/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Anaerobiose , Oxigênio/metabolismo
18.
J Mech Behav Biomed Mater ; 144: 105988, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37406484

RESUMO

The long-term successes of implant restorations rely on both appropriate osseointegration and robust soft tissue integration (STI). Numerous studies have reported that titanium dioxide nanotube (TNT) arrays formed by electrochemical anodization (EA) can promote early osteogenesis, but the mechanical stability of such modifications is often ignored and remains underexplored. In addition, relatively little research has been done on their effects on soft tissues integration. In this study, we developed mechanically robust TNT arrays using an optimized EA system. Subsequently, we immobilized a peptide, specifically D-amino K122-4, onto the anodized TNTs via polydopamine (PDA) films to enhance their mechanical properties. Surface morphology and composition were characterized by scanning electron microscopy (SEM), atomic force microscopy, and X-ray photoelectron spectroscopy. Mechanical properties, including the elastic modulus and hardness of TNTs modified Ti surfaces, were assessed using the nano-indention test. The adhesive strength of TNTs films to the substrate was measured using the nano scratch test. Furthermore, we evaluated the adhesion, spreading, and proliferation of human gingival fibroblasts (HGFs) and periodontal pathogenic bacteria such as Streptococcus mutans (S.m) and F. nucleatum (F.n) on the surface. Results showed that the elastic modulus, hardness, and adhesive strength of anodized TNTs were significantly enhanced by the incorporation of the D-amino K122-4 peptide. Live-dead staining and SEM observation suggested a decreased surface colonization by both bacterial species. The antibacterial rate of S.m and F. n was 81.5% and 71.7%, respectively, evaluated by colony counting method. Additionally, results of CCK8 assay showed that modified TNTs slightly stimulated HGFs attachment and proliferation while producing enhanced fluorescence of integrin ß1 and F-actin, confirmed by laser confocal microscopy observation. Thus, D-amino K122-4 biofunctionalized TNTs present significantly improved mechanical properties, and the mechanically robust structures modulate HGFs proliferation and alignment, resulting in decreased bacteria growth. This novel strategy has the potential to create a surface coating for implants that exhibits superior mechanical robustness and enhanced surface-to-implant interactions.


Assuntos
Implantes Dentários , Nanotubos , Humanos , Peptídeos , Titânio/química , Nanotubos/química , Fibroblastos , Bactérias , Propriedades de Superfície , Adesão Celular
19.
J Radiat Res ; 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154691

RESUMO

This study aimed to assess the severity of acute radiodermatitis (ARD) by ultrasound quantitative parameters and to try to identify the influencing factors of skin toxicity. A total of 55 patients who underwent radiotherapy after unilateral breast-conserving surgery (BCS) were included in the study. The irradiated side of the breast was used as the research object and the quantitative ultrasound parameters (skin thickness, shear wave elasticity) were evaluated before radiotherapy, every week during radiotherapy. Two weeks after radiotherapy, the patients were divided into two groups, according to the World Health Organization scoring standard: mild (0-2 grade) and severe (3-4 grade). The differences in the parameters between the groups and the changes during radiotherapy were compared, and the relationship between these parameters and the severity of ARD was analyzed. In addition, some clinical factors that may affect ARD were also included in our study. Ninety-eight percent of patients developed different degrees of ARD, and Group 2 accounted for ~31%. At the end of 5 weeks of radiotherapy, the difference in thickness between the two groups was statistically significant (P < 0.05). There was no significant change in the elastic modulus of breast skin between the two groups (P > 0.05). Body mass index >25 kg/m2, breast thickness ≥18 mm, skin basic elastic modulus <23 kPa and skin thickness increment >0.3 mm were considered to be associated with severe skin reactions (P < 0.05). Ultrasound can be a useful tool for the non-invasive and objective assessment of skin changes during radiotherapy, documenting quantitative changes in the skin of breast cancer patients following BCS undergoing radiotherapy.

20.
Sci Rep ; 13(1): 3346, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36849532

RESUMO

The purpose of this paper was to assess the value of ultrasonography in the prognosis of diffuse large b-cell lymphoma (DLBCL) by developing a new prognostic model. One hundred and eleven DLBCL patients with complete clinical information and ultrasound findings were enrolled in our study. Univariate and multivariate regression analyses were used to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curves were plotted and the corresponding area under the curve (AUC) was calculated to assess the accuracy of the international prognostic index (IPI) and new model in DLBCL risk stratification. The results suggested that hilum loss and ineffective treatment were independent risk variables for both PFS and OS in DLBCL patients. Additionally, the new model that added hilum loss and ineffective treatment to IPI had a better AUC for PFS and OS than IPI alone (AUC: 0.90, 0.88, and 0.82 vs. 0.71, 0.74, and 0.68 for 1-, 3-, and 5-year PFS, respectively; AUC: 0.92, 0.85 and 0.86 vs. 0.71, 0.75 and 0.76, for 1-, 3-, and 5-year OS, respectively). The model based on ultrasound images could better suggest PFS and OS of DLBCL, allowing for better risk stratification.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Ultrassonografia , Área Sob a Curva , Análise Multivariada
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