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1.
Biomacromolecules ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646768

RESUMO

Birefringent hydrogels have a strong potential for applications in biomedicine and optics as they can modulate the optical and mechanical anisotropy in confined two-dimensional geometries. However, production of birefringent hydrogels with hierarchical structures, mechanical properties, and biorelated behavior that are analogous to biological tissues is still challenging. Starting from the silk fibroin (SF)-ionic liquid solution system, this study aimed to rationally design a "binary solvent-exchange-induced self-assembly (BSEISA)" strategy to produce birefringent SF hydrogels (SFHs). In this method, the conformational transition rate of SF can be effectively controlled by the exchange rate of the binary solvents. Therefore, this method provides the possibility of controlling the conformation and orientation of SF. Molecular simulations confirmed that methanol is more effective in driving ß-sheet formation than other often used solvents, such as formic acid and water. The formed ß-sheets act as the physical cross-links that connect disparate protein chains, thereby forming continuous and stable three-dimensional (3D) hydrogel networks. The resultant BSEISA-SFHs are transparent and birefringent with mechanical characteristics similar to those of soft biological tissues, such as lens and cartilage. Interestingly, our results revealed that the evolution of experimental birefringent fringes perfectly matched the changes in stress distribution predicted using finite element analysis. Owing to the unique birefringence of BSEISA-SFHs, together with the advantages in mechanical performance, these hydrogels are anticipated to act as good tissue surrogates for understanding the mechanical response of biological tissues.

2.
PLoS One ; 16(3): e0247074, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33647031

RESUMO

OBJECTIVE: To study the feasibility of use of radiomic features extracted from axillary lymph nodes for diagnosis of their metastatic status in patients with breast cancer. MATERIALS AND METHODS: A total of 176 axillary lymph nodes of patients with breast cancer, consisting of 87 metastatic axillary lymph nodes (ALNM) and 89 negative axillary lymph nodes proven by surgery, were retrospectively reviewed from the database of our cancer center. For each selected axillary lymph node, 106 radiomic features based on preoperative pharmacokinetic modeling dynamic contrast enhanced magnetic resonance imaging (PK-DCE-MRI) and 5 conventional image features were obtained. The least absolute shrinkage and selection operator (LASSO) regression was used to select useful radiomic features. Logistic regression was used to develop diagnostic models for ALNM. Delong test was used to compare the diagnostic performance of different models. RESULTS: The 106 radiomic features were reduced to 4 ALNM diagnosis-related features by LASSO. Four diagnostic models including conventional model, pharmacokinetic model, radiomic model, and a combined model (integrating the Rad-score in the radiomic model with the conventional image features) were developed and validated. Delong test showed that the combined model had the best diagnostic performance: area under the curve (AUC), 0.972 (95% CI [0.947-0.997]) in the training cohort and 0.979 (95% CI [0.952-1]) in the validation cohort. The diagnostic performance of the combined model and the radiomic model were better than that of pharmacokinetic model and conventional model (P<0.05). CONCLUSION: Radiomic features extracted from PK-DCE-MRI images of axillary lymph nodes showed promising application for diagnosis of ALNM in patients with breast cancer.

3.
J Magn Reson Imaging ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559371

RESUMO

BACKGROUND: Several published studies have shown alterations of brain development in third-trimester fetuses with congenital heart disease (CHD). However, little is known about the timing and pattern of altered brain development in fetuses with CHD. PURPOSE: To investigate the changes in the volume of intracranial structures in fetuses with CHD by three-dimensional (3D) volumetric magnetic resonance imaging (MRI) in the earlier stages of pregnancy (median gestational age [GA], 26 weeks). STUDY TYPE: Retrospective. POPULATION: Forty women carrying a fetus with CHD (including 20 fetuses with GA <26 weeks) and 120 pregnant women carrying a healthy fetus (including 50 fetuses with GA <26 weeks). FIELD STRENGTH/SEQUENCE: Two-dimensional single-shot turbo spin echo sequence at 1.5 -T. ASSESSMENT: Three-dimensional volumetric parameters from slice-to-volume registered images, including cortical gray matter volume (GMV), subcortical brain tissue volume (SBV), intracranial cavity volume (ICV), lateral ventricles volume (VV), cerebellum, brainstem, and extra-cerebrospinal fluid (e-CSF) were quantified by manual segmentation from one primary and two secondary observers. STATISTICAL TESTS: Volumes were presented graphically with quadratic curve fitting. Scatterplots were produced mapping volumes against GA in normal and CHD fetuses. For GA <26 weeks, Z scores were calculated and Student's t-tests were conducted to compare volumes between the normal and CHD fetuses. RESULTS: In fetuses with CHD GMV, SBV, cerebellum, and brainstem were significantly reduced (all P < 0.05) in early stages of pregnancy (GA <26 weeks), with differences becoming progressively greater with increasing GA. Compared with normal fetuses, e-CSF, e-CSF to ICV ratio, and VV were higher in fetuses with CHD (all P < 0.05). However, ICV volume and the GMV to SBV ratio were not significantly reduced in the CHD group (P = 0.94 and P = 0.13, respectively) during the middle gestation (GA <26 weeks). DATA CONCLUSION: There appear to be alterations of brain development trajectory in CHD fetuses that can be detected by 3D volumetric MRI in the earlier stages of pregnancy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

4.
Biochem Pharmacol ; : 114466, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610591

RESUMO

Cardiac microvascular endothelial cells (CMECs), derived from coronary circulation microvessel, are the main barrier for the exchange of energy and nutrients between myocardium and blood. However, microvascular I/R injury is a severely neglected topic, and few strategies can reverse this pathology. In this study, we investigated the mechanism of shear stress in microvascular I/R injury, and try to elucidate the downstream signaling pathways that inhibit CMECs apoptosis to reduce I/R injury. Our results demonstrated that shear stress inhibited the apoptosis protein, increased PECAM-1 expression and eNOS phosphorylation in hypoxia reoxygenated (H/R) CMECs. The mechanism of shear stress was related to up-regulated expression of YAP, the increased number of YAP entering the nucleus by dephosphorylation, the reduced number of TUNEL positive cells, increased miR-206 and inhibited protein level of PDCD4 in CMECs. However, siRNA-mediated knockdown of YAP abolished the protective effects of shear stress on CMECs apoptosis, similar results obtained from administration with AMO-miR-206, and also prevented PDCD4 (target gene of miR-206) increasing when treatment with both AMO-miR-206 and mimics-miR-206. In vivo, restoring the blood fluid with nitroglycerin (NTG) to mimic in vitro shear stress levels, which subsequently improved cardiac function, reduced infarcted area, lowered microvascular perfusion defects. Functional investigations clearly illustrated that increased the protein expression of PECAM-1 and eNOS phosphorylation, activated YAP, strengthened miR-206 expression, and suppressed PDCD4 expression. In summary, this study confirmed that shear stress reversed CMECs apoptosis, relieved microvascular I/R injury, the mechanism of which involving through YAP/miR-206/PDCD4 signaling pathway to finally suppress myocardial I/R injury.

5.
Opt Lett ; 46(4): 900-903, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577543

RESUMO

To date, color-tunable photon upconversion (UC) in a single nanocrystal (NC) still suffers from cumbersome structures. Herein, we prepared a compact two-layer NC with bright and high-purity red and green UC emission upon 980 and 1530 nm excitation, respectively. The effects of trace Tm3+ doping and inert-shell coating on the UC color and intensity were discussed. In addition, the color tuning via various dual-excitation configurations and the color stability with temperature and excitation intensity were demonstrated. The proposed UC NC, featuring compact structure and high-quality color tuning, can lower the synthesis time cost and difficulty of its kind and can find wide applications in multi-channel imaging, display devices, anti-counterfeiting, and so on.

6.
Magn Reson Imaging ; 78: 18-24, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33556484

RESUMO

BACKGROUND: To evaluate 3-dimensional amide proton transfer weighted (APTw) imaging for type I endometrial carcinoma (EC), and investigate correlations of Ki-67 labelling index with APTw and intravoxel incoherent motion (IVIM) imaging. METHODS: 54 consecutive patients suspected of endometrial lesions underwent pelvic APTw and IVIM imaging on a 3 T MR scanner. APTw values and IVIM-derived parameters (Dt, D*, f) were independently measured by two radiologists on 22 postoperative pathological confirmed of type I EC lesions. Results were compared between histological grades and Ki-67 proliferation groups. ROC analysis was performed. Pearson's correlation analysis was performed for APTw values and IVIM-derived parameters with Ki-67 labeling index. RESULTS: APTw values and Dt, D*, f of all type I EC were 2.9 ± 0.1%, 0.677 ± 0.027 × 10-3 mm2/s, 31.801 ± 11.492 × 10-3 mm2/s, 0.179 ± 0.050 with inter-observer ICC 0.996, 0.850, 0.956, 0.995, respectively. APTw values of Ki-67 low-proliferation group (<30%, n = 8) were 2.5 ± 0.2%, significantly lower than the high-proliferation group (>30%, n = 14) with APTw values of 3.1 ± 0.1% (p = 0.016). Area under the curve was 0.768. APTw values of type I EC were moderately positively correlated with Ki-67 labelling index (r = 0.583, p = 0.004). There was no significant difference of Dt (p = 0.843), D* (p = 0.262), f (p = 0.553) between the two groups. No correlation was found between IVIM-derived parameters and Ki-67 labelling index (Dt, p = 0.717; D* p = 0.151; f, p = 0.153). CONCLUSION: 3D TSE APTw imaging is a feasible approach for detecting type I EC. Ki-67 labeling index positively moderately correlates with APTw not with IVIM.

7.
Signal Transduct Target Ther ; 6(1): 6, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33414372

RESUMO

Primary pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare non-small cell lung cancer (NSCLC) subtype. Clinical features have been described in our previous report, but molecular characteristics remain unclear. Herein, pLELC genomic features were explored. Among 41,574 lung cancers, 128 pLELCs and 162 non-pLELC NSCLCs were enrolled. Programmed cell death ligand 1 (PD-L1) and protein 53 (p53) expression was detected in 47 surgically resected pLELC samples by immunohistochemical assays. Multiomics genomic analyses, including whole-genome sequencing (WGS), RNA whole-transcriptome sequencing (RNA-seq), and Epstein-Barr virus (EBV) integration analyses, were performed on eight frozen pLELC tissues and compared with 50 lung adenocarcinomas (LUADs) and 50 lung squamous cell carcinomas (LUSCs) from The Cancer Genome Atlas (TCGA) and another 26 EBV-positive nasopharynx cancers (EBV+-NPCs). Progression-free survival (PFS) and overall survival (OS) of pLELC patients were better than those of non-pLELC patients. High PD-L1 or p53 expression was associated with extended disease-free survival (DFS). pLELC had 14 frequently mutated genes (FMGs). Somatically mutated genes and enrichment of genetic lesions were found, which differed from observations in LUAD, LUSC, and EBV+-nasopharyngeal carcinoma (NPC). Three tumor-associated genes, zinc finger and BTB domain-containing 16 (ZBTB16), peroxisome proliferator activated receptor gamma (PPARG), and transforming growth factor beta receptor 2 (TGFBR2), were downregulated with copy number variation (CNV) loss. EBV was prone to integrating into intergenic and intronic regions with two upregulated miR-BamH1-A rightward transcripts (BARTs), BART5-3P and BART20-3P. Our findings reveal that pLELC has a distinct genomic signature. Three tumor-associated genes with CNV loss and two miR-BARTs might be involved in pLELC tumorigenesis.

8.
Phytochemistry ; 183: 112628, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33412403

RESUMO

Nine undescribed guaiane-type sesquiterpenoids stelleraterpenoids A‒I, along with seven reported congeners, were isolated and identified from the 70% EtOH extract of the roots of Stellera chamaejasme L. Their chemical structures were elucidated on the basis of various spectral data. The relative configurations were determined by their NOESY spectra and comparison between their experimental and calculated NMR data. The absolute configurations were established by the comparison between the experimental and calculated ECD spectra and further by X-ray single-crystal diffraction analysis. The neuroprotective effects of these compounds on the H2O2-induced damage in human neuroblastoma SH-SY5Y cells were evaluated. Stelleraguaianone B exhibited the better activity with 71.62% cell viability compared to the positive control Trolox (65.05%) at 12.5 µM, which might be achieved by inhibiting the apoptosis of SH-SY5Y cells based on an annexin V-FITC/PI staining experiment.


Assuntos
Fármacos Neuroprotetores , Sesquiterpenos , Thymelaeaceae , Peróxido de Hidrogênio , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano
9.
Ecotoxicol Environ Saf ; 207: 111562, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254416

RESUMO

BACKGROUND: Low benzene exposure leads to hematotoxicity, but we still lack sensitive early monitoring and early warning markers. Benzene is associated with inflammation, which is mainly mediated by cytokines network. However, until now few studies have conducted high-throughput detection of multi-cytokines to get a global view of cytokine changes and screen for markers of benzene-induced toxicity. We hypothesized that cytokine profiles mediate benzene-induced hematotoxicity. METHODS: 228 subjects consisting of 114 low benzene exposed workers and 114 healthy controls were recruited at Research Center of Occupational Medicine, Peking University Third Hospital, Beijing. The serum concentrations of 27 cytokines were detected by cytokinomics array, urinary benzene series metabolites were measured by UPLC-MS/MS, and peripheral blood cell counts were observed by basic blood test. RESULTS: Among 27 cytokines, IL-9 and MIP1-α were significantly lower, but IL-4, IL-10, IL-15, MCP-1, TNF-α and VEGF were significantly higher in benzene exposure group than controls. Urinary benzene metabolite S-phenylmercapturic acid (S-PMA) was significantly higher in benzene exposure group and had a negative linear relationship with WBC count. S-PMA was only significantly associated with IL-9, meanwhile IL-9, IL-15 and VEGF had a positive linear relationship with WBC count. The bootstrapping mediation models showed that the effect of S-PMA on WBC count was partially explained by IL-9 for 10.11%. CONCLUSION: This study suggests that exposure to benzene was associated with alternation of blood cell count and cytokine profiles in workers exposed to low levels of benzene, especially decreases of WBC count and IL-9. We also found IL-9 partially mediated the effect of low benzene exposure on WBC count, which may be a potential and promising early monitoring and early warning marker of benzene hematotoxicity.


Assuntos
Poluentes Ocupacionais do Ar/metabolismo , Benzeno/metabolismo , Citocinas/sangue , Exposição Ocupacional/análise , Acetilcisteína/análogos & derivados , Adulto , Grupo com Ancestrais do Continente Asiático , Benzeno/análise , Biomarcadores/urina , Contagem de Células Sanguíneas , Cromatografia Líquida , Estudos Transversais , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Espectrometria de Massas em Tandem
10.
Cell ; 184(2): 489-506.e26, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33338423

RESUMO

Single-cell transcriptomics has been widely applied to classify neurons in the mammalian brain, while systems neuroscience has historically analyzed the encoding properties of cortical neurons without considering cell types. Here we examine how specific transcriptomic types of mouse prefrontal cortex (PFC) projection neurons relate to axonal projections and encoding properties across multiple cognitive tasks. We found that most types projected to multiple targets, and most targets received projections from multiple types, except PFC→PAG (periaqueductal gray). By comparing Ca2+ activity of the molecularly homogeneous PFC→PAG type against two heterogeneous classes in several two-alternative choice tasks in freely moving mice, we found that all task-related signals assayed were qualitatively present in all examined classes. However, PAG-projecting neurons most potently encoded choice in cued tasks, whereas contralateral PFC-projecting neurons most potently encoded reward context in an uncued task. Thus, task signals are organized redundantly, but with clear quantitative biases across cells of specific molecular-anatomical characteristics.

11.
Cell Mol Biol Lett ; 25(1): 49, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33292168

RESUMO

AIM: To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism. METHODS: The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial-mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-ß is the target gene of miR-296-5p. Finally, TGF-ß expression plasmids were transfected into NPC cells to verify the role of TGF-ß in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis. RESULTS: Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-ß, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-ß and was significantly associated with the lymph node metastasis of patients with NPC. CONCLUSIONS: Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-ß. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.

12.
ACS Biomater Sci Eng ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33356118

RESUMO

Animal hairs, like other natural fibers, display excellent mechanical properties, especially, the tensile toughness and fracture resistance. Several structure-mechanics models have attributed mechanical superiority of hair to its unique nanocomposite structure which consists of intermediate filaments and matrix. However, the contribution of fibrils and their associated interfaces on the mechanical properties of animal hairs remains unclear. Herein, using the small- and wide-angle X-ray scattering, and an ultrahigh-speed microcamera system, it is confirmed that the conformation and fibrils (which represent both nanofibrils and microfibrils) of the keratin channel endow tensile toughness and fracture resistance to camel hairs. During the stretching process, an α-ß transition occurred at the secondary structure level, leading to the formation of a tensile plateau, which improves the toughness compared with the structure without a conformation transition. Meanwhile, fibrils further toughened the camel hairs and resisted their crack propagation through confined fibrillar slippage, splitting, and pulling. These structure-property relations in natural hairs can inspire damage-tolerant polymer fiber design.

13.
J Clin Pathol ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33372106

RESUMO

AIMS: Considering morphological heterogeneity of lung adenocarcinoma (LUAD) and no objective prognostic grading system existing currently, we aim to establish an 'optimised architecture-based grading system' (OAGS) to predict prognosis for resected LUAD. METHODS: A multicentral study involving three independent cohorts of LUAD was conducted. Predictive ability of the OAGS for recurrence-free probability (RFP) and overall survival (OS) was assessed in training cohort (n=228) by the area under the receiver operating characteristic curve (AUC), Harrell's concordance index (C-index) and Kaplan-Meier survival analyses, which was validated in testing (n=135) and validation (n=226) cohorts. RESULTS: The OAGS consists of: grade 1 for lepidic, papillary or acinar predominant tumour with no or less than 5% of high-grade patterns (cribriform, solid and or micropapillary), grade 2 for lepidic, papillary or acinar predominant tumour with 5% or more of high-grade patterns, and grade 3 for cribriform, solid or micropapillary predominant tumour. In all stages, the OAGS outperformed the pattern-dominant grading system and IASLC grading system for predicting RFP (C-index, 0.649; AUC, 0.742) and OS (C-index, 0.685; AUC, 0.754). Multivariate analysis identified it as an independent predictor of both (RFP, p<0.001; OS, p<0.001). Furthermore, in pT1-2aN0M0 subgroup, the OAGS maintained its ability to predict recurrence (C-index, 0.699; AUC, 0.769) and stratified patients into different risk groups of RFP (p<0.001). These results were confirmed in testing and validation cohorts. CONCLUSIONS: The OAGS is an independent prognostic factor and shows a robust ability to predict prognosis for resected LUAD.

14.
PLoS One ; 15(12): e0244222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33351838

RESUMO

Grassland is one of the most widely-distributed ecosystems on Earth and provides a variety of ecosystem services. Grasslands, however, currently suffer from severe degradation induced by human activities, overgrazing pressure and climate change. In the present study, we explored the transcriptome response of Stipa breviflora, a dominant species in the desert steppe, to grazing through transcriptome sequencing, the development of simple sequence repeat (SSR) markers, and analysis of genetic diversity. De novo assembly produced 111,018 unigenes, of which 88,164 (79.41%) unigenes were annotated. A total of 686 unigenes showed significantly different expression under grazing, including 304 and 382 that were upregulated and downregulated, respectively. These differentially expressed genes (DEGs) were significantly enriched in the "alpha-linolenic acid metabolism" and "plant-pathogen interaction" pathways. Based on transcriptome sequencing data, we developed eight SSR molecular markers and investigated the genetic diversity of S. breviflora in grazed and ungrazed sites. We found that a relatively high level of S. breviflora genetic diversity occurred under grazing. The findings of genes that improve resistance to grazing are helpful for the restoration, conservation, and management of desert steppe.

15.
Nucleic Acids Res ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33221906

RESUMO

Long non-coding RNAs (lncRNAs) play important functional roles in many diverse biological processes. However, not all expressed lncRNAs are functional. Thus, it is necessary to manually collect all experimentally validated functional lncRNAs (EVlncRNA) with their sequences, structures, and functions annotated in a central database. The first release of such a database (EVLncRNAs) was made using the literature prior to 1 May 2016. Since then (till 15 May 2020), 19 245 articles related to lncRNAs have been published. In EVLncRNAs 2.0, these articles were manually examined for a major expansion of the data collected. Specifically, the number of annotated EVlncRNAs, associated diseases, lncRNA-disease associations, and interaction records were increased by 260%, 320%, 484% and 537%, respectively. Moreover, the database has added several new categories: 8 lncRNA structures, 33 exosomal lncRNAs, 188 circular RNAs, and 1079 drug-resistant, chemoresistant, and stress-resistant lncRNAs. All records have checked against known retraction and fake articles. This release also comes with a highly interactive visual interaction network that facilitates users to track the underlying relations among lncRNAs, miRNAs, proteins, genes and other functional elements. Furthermore, it provides links to four new bioinformatics tools with improved data browsing and searching functionality. EVLncRNAs 2.0 is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs2/.

16.
Mol Imaging Biol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185840

RESUMO

PURPOSE: To evaluate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging for differentiation of endometrial adenocarcinoma and uterine benign lesions. PROCEDURES: This prospective study enrolled 22 normal volunteers and 113 patients with suspicious uterine lesions, including endometrial adenocarcinoma, leiomyoma, and adenomyosis. Pelvic APTw MRI was performed on a 3-T MRI scanner with default APTw parameters. Two radiologists blindly evaluated uterine lesion APTw image quality by a 3-point Likert scale and independently measured APTw values on images with excellent to good image quality. Inter-reader agreement was evaluated. The Mann-Whitney U test with Bonferroni correction was used to compare the differences among different types of uterine lesions. A receiver operating characteristic analysis was performed. RESULTS: A total of 111 lesions (33 endometrial adenocarcinoma, 26 leiomyoma, and 52 adenomyosis lesions) from 99 patients revealing a majority of good quality with excellent inter-reader agreement were included for the image quality evaluation. APTw values of endometrial adenocarcinoma were 2.9 ± 0.1 %, significantly higher than those of leiomyoma (1.9 ± 0.1 %), adenomyosis (2.2 ± 0.1 %), and normal uterine myometrium (1.9 ± 0.1 %) (all p < 0.0001). The area under the receiver operating characteristic curve for differentiating endometrial adenocarcinoma from leiomyoma, adenomyosis, and myometrium was 0.87, 0.85, and 0.91, respectively. Feasible threshold APTw values of each group were determined as 2.4 %, 2.7 %, and 2.4 % with a sensitivity of 83.3 %, 76.7 %, and 83.3 % and a specificity of 83.3 %, 81.6 %, and 86.4 %, respectively. CONCLUSIONS: Malignant endometrial adenocarcinoma had significantly higher APTw values than leiomyoma, adenomyosis, and normal uterine myometrium. Our study adds to the growing body of validation on 3D APTw imaging and uterine lesions.

17.
BMC Mol Cell Biol ; 21(1): 80, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167868

RESUMO

BACKGROUND: Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis. RESULTS: High doses of arecoline (> 32 µg/ml) could inhibit human oral fibroblast proliferation, while low doses of arecoline (< 16 µg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was found to be both sufficient and necessary for the promotion of fibroblast proliferation. Egr-1 could mediate the expression of Wnt5a in fibroblasts, while NF-κB, FOXO1, Smad2, and Smad3 did not. Treatment with siRNAs specific to Egr-1, Egr inhibitors, or Wnt5a antibody treatment could all inhibit arecoline-induced Wnt5a upregulation and fibroblast proliferation. CONCLUSIONS: Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer.

18.
Front Oncol ; 10: 585738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194734

RESUMO

Purpose: To evaluate the predictive value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative parameters in treatment response to concurrent chemoradiotherapy (CCRT) for locally advanced cervical squamous cell carcinoma (LACSC). Methods and materials: LACSC patients underwent CCRT had DCE-MRI before (e0) and after 3 days of treatment (e3). Extended Tofts Linear model with a user arterial input function was adopted to generate quantitative measurements. Endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), and fractional plasma volume (Vp) were calculated, and percentage changes ΔKtrans, ΔKep, ΔVe, and ΔVp were computed. The correlations of these measurements with the tumor regression rate were analyzed. The predictive value of these parameters on treatment outcome was generated by the receiver operating characteristic (ROC) curve. Univariate and multivariate logistic regression analyses were conducted to find the independent variables. Results: Ktrans-e0, Kep -e0, ΔKtrans, and ΔVe were positively correlated with the tumor regression rate. Mean values of Ktrans-e0, Ktrans-e3, ΔKtrans, and ΔVe were higher in the non-residual tumor group than residual tumor group and were independent prognostic factors for predicting residual tumor occurrence. Ktrans-e3 showed the highest area under the curve (AUC) for treatment response prediction. Conclusions: Quantitative parameters at e0 and e3 from DCE-MRI could be used as potential indicators for predicting treatment response of LACSC.

19.
Macromol Rapid Commun ; : e2000435, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196127

RESUMO

The heat-induced self-assembly of silk fibroin (SF) is studied by combing fluorescence assessment, infrared nanospectroscopy, wide-angle X-ray scattering, and Derjaguin-Muller-Toporov coupled with atomic force microscopy. Several fundamental issues regarding the formation, structure, and mechanical performance of silk nanofibrils (SNFs) under heat-induced self-assembly are discussed. Accordingly, SF in aqueous solution is rod-like in shape and not micellar. The formation of SNFs occurs through nucleation-dependent aggregation, but the assembly period is variable and irregular. SF shows inherent fractal growth, and this trend is critical for the short-term assembly. The long-term assembly of SF, however, mainly involves an elongation growth process. SNFs produced by different methods, such as ethanol treatment and heat incubation, have similar secondary structure and mechanical properties. These investigations improve the in-depth understanding of fundamental issues related to self-assembly of SNFs, and thus provide inspiration and guidance in designing of silk nanomaterials.

20.
EClinicalMedicine ; 27: 100544, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33150321

RESUMO

Background: A comprehensive evaluation of the burden of inflammation bowel disease (IBD) is important for identifying potential strategies to control the disease. We present results from the Global Burden of Diseases (GBD) 2017 of IBD at the national level, the trends in disease burden and its epidemiological features in China. Methods: Using the methods and results from GBD 2017, we describe the IBD burden based on the prevalence, incidence, mortality, years of lost (YLLs), the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs) in China estimated using DisMod-MR 2·1. We additionally evaluated the rate of DALYs at national locations in 2017. Findings: From 1990 to 2017, the cases, deaths, YLLs, YLDs and DALYs for IBD in China were from 1,047,991 to 2,665,081, from 5701 to 5198, from 188,814 to 107,373, from 157,581 to 394,887, from 346,396 to 502,260, respectively. Increasing trends were observed in prevalence (APC: 2·9%), incidence (APC: 1·1%), DALYs (APC: 0·8%) and YLDs (APC:2·9%). There were decreasing trends in mortality (APC: -1·0%) and YLLs (APC: -2·7%). As to the age-standardized rates of DALYs, it observed a decreasing trend (APC: -0·78%). Similar trends were observed in men and women. The age-standardized APCs in incidence, mortality and rate of YLLs among women were higher than those among men. The age-standardized rate of DALYs was 27·51 per 100,000 in 2017. Interpretation: Between 1990 and 2017, China experienced a decrease in the age-standardized DALYs, mortality rates and YLLs due to IBD, despite an increase in the age-standardized rate of prevalence, incidence and YLDs. China is still one of the low endemic areas. Funding: This work had no supporting funding.

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