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1.
Biochim Biophys Acta Mol Cell Res ; 1868(1): 118878, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33011193

RESUMO

Ovarian cancer is the deadliest gynaecologic malignancy, and the five-year survival rate of patients is less than 35% worldwide. Cancer stem cells (CSCs) are a population of cells with stem-like characteristics that are thought to cause chemoresistance and recurrence. TRIM29 is aberrantly expressed in various cancers and associated with cancer development and progression. Previous studies showed that the upregulation of TRIM29 expression in pancreatic cancer is related to stem-like characteristics. However, the role of TRIM29 in ovarian cancer is poorly understood. In this study, we found that TRIM29 expression was increased at the translational level in both the cisplatin-resistant ovarian cancer cells and clinical tissues. Increased TRIM29 expression was associated with a poor prognosis of patients with ovarian cancer. In addition, TRIM29 could enhance the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells. Recruitment of YTHDF1 to m6A-modified TRIM29 was involved in promoting TRIM29 translation in the cisplatin-resistant ovarian cancer cells. Knockdown of YTHDF1 suppressed the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells, which could be rescued by ectopic expression of TRIM29. This study suggests TRIM29 may act as an oncogene to promote the CSC-like features of cisplatin-resistant ovarian cancer in an m6A-YTHDF1-dependent manner. Due to the roles of TRIM29 and YTHDF1 in the promotion of CSC-like features, they may become potential therapeutic targets to combat the recurrence of ovarian cancer.

2.
J Colloid Interface Sci ; 582(Pt A): 364-375, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32861041

RESUMO

Oral delivery of protein or peptide drugs confronts several barriers, the intestinal epithelium and the mucus barrier on the gastrointestinal tract is deemed to be the toughest obstacles. However, overcoming these two obstacles requires contradictory surface properties of a nanocarrier. In the present work, mesoporous silica nanoparticles (MSNs) were modified with deoxycholic acid (DC) and coated with sulfobetaine 12 (SB12) for the first time to achieve both improved mucus permeation and transepithelial absorption. MSNs modified with stearic acid and coated with dilauroylphosphatidylcholine (DLPC) or Pluronic P123 were also prepared as controls. The SB12 coated DC modified MSN had high drug loading of 22.2%. The zwitterion coating endows the MSN improved mucus penetrating ability. In addition, the carrier also showed remarkable affinity with epithelial cells. The cellular uptake was significantly improved (10-fold for Caco-2 cells and 8-fold for E12 cells). The results also indicated that the DC modified carrier was able to avoid entry into lysosomes. It can increase the absorption of loaded insulin in all intestine segments and showed outstanding hypoglycemic effect in diabetic rats. The results suggest the zwitterion-functionalized MSNs might be a good candidate for oral protein delivery.

3.
Chemosphere ; 262: 127924, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805661

RESUMO

Cr(VI) compounds at high temperature usually tend to decompose and reduce into Cr(III) due to thermodynamically instability for Cr(VI). This study found Cr(VI) could be reduced into Cr(V) instead of Cr(III) in the presence of CaO during heating solid waste containing Cr(VI). CaCrO4 is prepared and mixed with CaO as simulated solid waste containing Cr(VI). It was found that CaCrO4 reacted with CaO and formed a new product Ca5(CrO4)3O0.5 at temperature range of 800 and 1000 °C. The valence state of Cr in Ca5(CrO4)3O0.5 is determined to be +5 b y XPS analysis, and the color for new formed Cr(V) is observed in green, similar to Cr(III) compounds. The temperature and CaO are two keys to arouse the reduction reaction of Cr(VI) into Cr(V). In particular, the reduction of Cr(VI) into Cr(V) is strongly depended on temperature (800-1000 °C), this reaction can be balanced within 10 min, while prolonging sintering time has little help for promoting the reduction of Cr(VI) to Cr(V). Additionally, it was found Cr(V) can keep stable and not be re-oxidized into Cr(VI) at 800-1000 °C. Above results offers some new understanding and knowledge about the formation of Cr(V) in presence of much CaO or CaCO3 during heating solid waste containing Cr(VI).


Assuntos
Cromo/química , Eliminação de Resíduos/métodos , Hidróxido de Cálcio/química , Calefação , Temperatura Alta , Oxirredução , Resíduos Sólidos , Temperatura
4.
Sci Total Environ ; 753: 141746, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33207482

RESUMO

This study explored the effects of adding phosphogypsum (PPG), medical stone (MS), and both (PPM) during composting on nitrogen transformation, nitrogen functional genes, the bacterial community, and their relationships with NH3 and N2O emissions. Adding MS and PPM reduced NH3 emissions by 25.78-68.37% and N2O emissions by 19.00-42.86%. PPG reduced NH3 emissions by 59.74% but slightly increased N2O emissions by 8.15%. MS was strongly correlated with the amoA-dominated nitrification process. PPG and PPM had strong correlations with nirS- and nirK-dominated, and nosZ-dominated denitrification processes, respectively. PPM promoted nitrification and denitrification processes more than PPG and MS. Different functional bacteria had key roles in nitrification and denitrification during different composting stages. Firmicutes probably contributed to the conversion and release of nitrogen in the thermophilic period, whereas Proteobacteria, Chloroflexi, Bacteroidetes, and other phyla might have played important roles in the cooling and maturation periods. PPM obtained the greatest reductions in NH3 and N2O release via the regulation of environmental variables, nitrogen functional genes, and the bacterial community. Overall, these results provide insights at a molecular level into the effects of PPG and MS on nitrogen transformation and NH3 and N2O emissions during composting.


Assuntos
Compostagem , Bactérias/genética , Sulfato de Cálcio , Desnitrificação , Genes Bacterianos , Nitrificação , Nitrogênio , Óxido Nitroso/análise , Fósforo , Solo
5.
Sci Total Environ ; 752: 142162, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33207525

RESUMO

The present study compared the effects of adding shrimp shell powder (SSP) at four levels comprising 0% (CK), 5% (L), 10% (M), and 15% (H) on the abundance of antibiotic resistance genes (ARGs) and the bacterial community succession during swine manure composting. The relative abundances of 5/11 ARGs were reduced in CK, and 7/11 in H. Moreover, the removal rate was enhanced by adding SSP. Thus, H decreased the total abundance of ARGs by 32.68%, whereas CK increased it by 6.31%. Redundancy analysis indicated that mobile genetic elements (MGEs) (46.6%) and the bacterial community (31.1%) mainly explained the changes in ARGs. H enhanced the removal of MGEs, prolonged the thermophilic phase, stabilized copper and zinc, and retained nitrogen. LEfSe analysis and non-metric multidimensional scaling indicated that the bacterial community changed in the composting process, and it was optimized by H. The abundances of the potential bacterial co-hosts (such as Lactobacillus, Corynebacterium_1, and Ornithinicoccus) of ARGs and MGEs were lower and the decomposition of organic matter was higher in H compared with CK. Thus, composting with 15% SSP can reduce the risk of ARGs and improve the practical value for agronomic application.


Assuntos
Compostagem , Animais , Antibacterianos , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Esterco , Suínos
6.
Abdom Radiol (NY) ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151359

RESUMO

PURPOSE: In the clinical management of patients with locally advanced rectal cancer (LARC), the early identification of poor and good responders after neoadjuvant chemoradiotherapy (N-CRT) is essential. Therefore, we developed and validated predictive models including MRI findings from the structured report template, clinical and radiomics parameters to differentiate between poor and good responders in patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. METHODS: Preoperative multiparametric MRI from 183 patients with locally advanced rectal cancer (122 in the training cohort, 61 in the validation cohort) was included in this retrospective study. After preprocessing, radiomic features were extracted and two methods of feature selection was applied to reduce the number of radiomics features. Logistic regression (LR) and random forest (RF) machine learning classifiers were trained to identify good responders from poor responders. Multivariable logistic regression analysis was used to incorporate the radiomic signature and clinical risk factors into a nomogram. Classifier performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: For the differentiation of poor and good responders, the radiomics model with an LR classifier achieved AUCs of 0.869 and 0.842 for the training and validation cohorts, respectively. The nomogram showed the highest reproducibility and prognostic ability in the training and validation cohorts, with AUCs of 0.923 (95% confidence interval, 0.872-0.975) and 0.898 (0.819-0.978), respectively. Additionally, the nomogram achieved significant risk stratification of patients in respect to progression free survival (PFS). CONCLUSIONS: The nomogram accurately differentiated good and poor responders in patients with LARC undergoing N-CRT, and showed significant performance for predicting PFS.

7.
Nanoscale ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155601

RESUMO

Accurate determination of the atomic spatial configuration of Frenkel defects is important for understanding the mechanism and fully utilizing these defects to optimize the material properties. In this study, aberration-corrected scanning transmission electron microscopy (STEM) was used to identify the Fe vacancies and Fe Frenkel defect pairs, which have not been previously investigated, in NiFe2O4 (NFO). The spatial distribution of these point defects is determined by comparing the experimental and simulated images, where the experimental image intensities are consistent with the calculated image intensities. We confirmed the stabilities of the observed point defect configurations and calculated their electronic structures using density functional theory. A comprehensive understanding of the relationship between the Frenkel defect spatial configurations and electronic properties is obtained, which provides an alternative method to regulate the NFO performance.

9.
Life Sci ; : 118728, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33160992

RESUMO

AIMS: Diabetic nephropathy (DN) is the most frequent complication of diabetes and causes millions of deaths each year. Finding novel therapy to DN is urgent, which requires a good understanding of the pathogenesis. Aims are to investigate the molecular mechanisms of DN by focusing on ANRIL/miR-497/TXNIP axis. MAIN METHODS: Kidney tissues were collected from diagnosed DN patients. High glucose (HG) treatment of human renal tubular epithelial cell cells (HK-2) was used as the cell model of DN. qRT-PCR and Western blotting were performed to measure levels of ANRIL, miR-497, TXNIP, IL-1ß, IL-18, caspase-1, and NLRP3. LDH leakage and cell viability were determined with commercial LDH activity kit and MTT assay. ELISA was employed to examine secreted IL-1ß and IL-18 levels. Flow cytometry was used to examine caspase-1 activity. Dual luciferase assay was performed to validate interactions of ANRIL/miR-497 and miR-497/TXNIP. KEY FINDINGS: ANRIL and TXNIP were elevated in DN kidney tissues and HG-treated HK-2 cells while miR-497 was reduced. ANRIL bound miR-497 while miR-497 directly targeted TXNIP. Knockdown of ANRIL suppressed HG-induced LDH leakage, TXNIP/NLRP3/caspase-1 activation, and increases of IL-1ß and IL-18 secreted levels. miR-497 knockdown or TXNIP overexpression reversed the effects of ANRIL knockdown on LDH leakage and pyroptosis-related signaling. miR-497 mimics inhibited caspase-1-dependent pyroptosis while co-overexpression of TXNIP blocked its effects in HG-treated HK-2 cells. SIGNIFICANCE: ANRIL promotes pyroptosis and kidney injury in DN via acting as miR-497 sponge to disinhibit TXNIP expression. These results shed light on the mechanisms of DN and provide targets for therapy development.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33131039

RESUMO

This work was aimed at investigating the feasibility of the slope wetland system (SWs) for improving the polluted river water. According to the characteristics of polluted river water with different hydraulic retention time (HRT) changes, a field simulation device was set up. In this experiment, a SWs simulation device was set up to study pollutant removal of SWs under different hydraulic conditions. It was found that the effect of mixed fillers (zeolite and ceramsite) as the bed was better than that of the gravel fillers as the bed. The improvement of each treatment index was about 5% (P < 0.05). When HRT = 5 days, the removal rate of chemical oxygen demand (COD) was 28.02%, total nitrogen (TN) was 32.99%, ammonia nitrogen (NH3-N) was 32.49%, and total phosphorus (TP) was 38.15%. At the same time, it was found that the characteristic moderate extension of HRT is conducive to the removal of pollutants in SWs. The growth of plants in the environment of the gravel matrix was worse than that of mixed fillers (zeolite and ceramsite). It was found that physical adsorption was the main form of pollution removal on the SWs fillers by Fourier infrared spectrum (FTIR) analysis. Based on the analysis of the microbial community in the packing of the device, it is indicated that the enrichment of microorganisms appeared during the experiment, forming the dominant bacteria against the polluted river water.

11.
Int J Rheum Dis ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146461

RESUMO

OBJECTIVES: Mannose binding lectin (MBL) gene single nucleotide polymorphisms have been associated with systemic lupus erythematosus (SLE) risk with inconsistent results. This study aimed to explore whether MBL2 A\B, A\C, A\D, A\O, L\H and Y\X polymorphisms affected SLE susceptibility. METHODS: A meta-analysis was performed on 20 studies, containing allelic contrast, additive, dominant and recessive models. Odds ratio (OR) was calculated to reflect the effect of association. RESULTS: A total of 64 pooled comparisons were conducted, including 7194 SLE patients and 7401 healthy controls. The meta-analysis inducted a significant association between allele B and SLE (OR = 0.766, 95% CI = 0.681-0.862, P < .001). The genotype BB in the additive model and AB + BB in the recessive model both reduced the risk of SLE (OR = 0.611, 95% CI = 0.422-0.882, P = .009; OR = 0.806, 95% CI = 0.688-0.944, P = .008). Regarding A\O polymorphisms, results revealed statistical differences in allelic contrast, additive model and recessive models (OR = 0.826, 95% CI = 0.732-0.931, P = .002; OR = 0.737, 95% CI = 0.557-0.977, P = .034 and OR = 0.793, 95% CI = 0.683-0.921, P = .002, respectively). As for L\H, meta-analysis revealed that allele H and genotype HH both decreased SLE susceptibility in allelic contrast and dominant models (OR = 1.463, 95% CI = 1.097-2.007, P = .018; OR = 1.383, 95% CI = 1.124-1.701, P = .002). Stratification by ethnicity indicated that allele H related to SLE in European populations (OR = 0.736, 95% CI = 0.617-0.879, P = .001), and the recessive model correlated with SLE in Asians (OR = 0.808, 95% CI = 0.667-0.979, P = .03). CONCLUSION: The present study suggests that A\B and A\O polymorphisms were associated with SLE susceptibility, and the allele H may be a protective factor in SLE.

12.
J Environ Manage ; : 111560, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33172706

RESUMO

This study assessed the effects of superphosphate (SPP) and phosphogypsum (PPG) on the bacterial and fungal community succession and molecular ecological networks during composting. Adding SPP and PPG had positive effects on the bacterial richness and diversity, negative effects on the fungal richness and diversity. The microbial diversity and richness were higher in PPG than SPP. Non-metric multidimensional scaling analysis clearly separated SPP and PPG from the control treatment with no additives. The dominant genera comprised Turicibacter, Bacillus, norank_o_SBR1031, Thermobifida, norank_f_Limnochordaceae, Truepera, Thermopolyspora, Mycothermus, Dipodascus, Thermomyces, and unclassified_p_Ascomycota. In all treatments, the major bacterial species differed clearly in the later thermophilic, cooling, and maturation composting stages, whereas the main fungal species varied significantly in the thermophilic stage. The changes in the dominant microorganisms in SPP and PPG may have inhibited or promoted the degradation of organic matter during various composting stages. Adding SPP and PPG led to more complex bacterial networks and less complex fungal networks, where SPP had more adverse effects on the fungal networks than PPG. SPP and PPG could potentially alter the co-occurrence patterns of the bacterial and fungal communities by changing the most influential species. SPP and PPG changed the composition and succession of the microbial community by influencing different physiochemical properties during various composting stages where the pH was the main explanatory factor. Overall, this study provides new insights into the effects of SPP and PPG on the microbial community and its interactions during composting.

13.
Int J Biol Sci ; 16(16): 3184-3199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162824

RESUMO

Background: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. Methods and results: We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocytes. We also demonstrated that MPT0B291 suppressed proliferation by inducing G1 phase cell cycle arrest and increased apoptosis in human and rat glioma cell lines by flow cytometry and immunocytochemistry. We further investigated the anti-tumor effects of MPT0B291 in xenograft (mouse) and allograft (rat) models. The IVIS200 images and histological analysis indicated MPT0B291 (25 mg/kg, p. o.) reduced tumor volume. Mechanistically, MPT0B291 increased phosphorylation and acetylation/activation of p53 and increased mRNA levels of the apoptosis related genes PUMA, Bax, and Apaf1 as well as increased protein level of PUMA, Apaf1 in C6 cell line. The expression of cell cycle related gene p21 was also increased and Cdk2, Cdk4 were decreased by MPT0B291. Conclusion: Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth.

14.
Pharmacol Res ; : 105286, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33157234

RESUMO

Alcohol consumption is one of the risk factors for kidney injury. The underlying mechanism of alcohol-induced kidney injury remains largely unknown. We previously found that the kidney in a mouse model of alcoholic kidney injury had severe inflammation. In this study, we found that the administration of alcohol was associated with the activation of NLRP3 inflammasomes and NF-κB signaling, and the production of pro-inflammatory cytokines. Whole-genome methylation sequencing (WGBS) showed that the DNA encoding fat mass and obesity-associated protein (FTO) was significantly methylated in the alcoholic kidney. This finding was confirmed with the bisulfite sequencing (BSP), which showed that alcohol increased DNA methylation of FTO in the kidney. Furthermore, inhibition of DNA methyltransferases (DNMTs) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified peroxisome proliferator activated receptor-α (PPAR-α) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-α m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-κB-driven renal inflammation in the kidney. These findings may provide novel strategies for preventing and treating alcoholic kidney diseases.

15.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4792-4797, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164447

RESUMO

"Shengdeng" is a traditional Tibetan medicine, which has many synonyms. It is complex in origin and serious in mi-xing. In order to clarify the origin of "Shengdeng" and its medicinal use, this paper makes a textual research on the name, variety and efficacy of "Shengdeng" by consulting Tibetan medicine classics such as The Four Medical Trantras and Jingzhu Materia Medica, combined with modern literature of Tibetan medicine. It is clear that the synonyms, primitive species, mainstream varieties and functions of Tibetan medicine "Shengdeng". The collation and analysis of the literature shows that "Shengdeng" has effects of treating rheumatism, drying "Huangshui", detumescence and relieving pain, and is mainly used for the treatment of rheumatoid arthritis in Tibetan medicine. Its original varieties include 14 species of plants belonging to 6 families: Spicaceae, Rhamnaceae, Cephalotaxus, Leguminosae, Hematoxylaceae and Taxaceae. Combined with the collection of legal standards at all levels, the distribution of resources and the application of clinical prescriptions, it is considered that the mainstream species of "Shengdeng" are Rhamnella gilgitica, Xanthoceras sorbifolia, Rhamnus parvifolia. As a substitute, Acacia catechu is also widely used in clinic. The literature review and variety textual research on Tibetan medicine "Shengdeng" is helpful to improve the safety, effectiveness and quality controllability of its clinical application, and provide scientific basis for its further standard setting, pharmacodynamics research, new drug development and so on.


Assuntos
Fabaceae , Plantas Medicinais , Rhamnaceae , Dessecação , Medicina Tradicional Tibetana
16.
Sensors (Basel) ; 20(22)2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33198204

RESUMO

The arterial wall elastance is an important indicator of arterial stiffness and a kind of manifestation associated with vessel-related disease. The time-varying arterial wall elastances can be measured using a multiple-frequency vibration approach according to the Voigt and Maxwell model. However, such a method needs extensive calculation time and its operating steps are very complex. Thus, the aim of this study is to propose a simple and easy method for assessing the time-varying arterial wall elastances with the single-frequency vibration approach. This method was developed according to the simplified Voigt and Maxwell model. Thus, the arterial wall elastance measured using this method was compared with the elastance measured using the multiple-frequency vibration approach. In the single-frequency vibration approach, a moving probe of a vibrator was induced with a radial displacement of 0.15 mm and a 40 Hz frequency. The tip of the probe directly contacted the wall of a superficial radial artery, resulting in the arterial wall moving 0.15 mm radially. A force sensor attached to the probe was used to detect the reactive force exerted by the radial arterial wall. According to Voigt and Maxwell model, the wall elastance (Esingle) was calculated from the ratio of the measured reactive force to the peak deflection of the displacement. The wall elastances (Emultiple) measured by the multiple-frequency vibration approach were used as the reference to validate the performance of the single-frequency approach. Twenty-eight healthy subjects were recruited in the study. Individual wall elastances of the radial artery were determined with the multiple-frequency and the single-frequency approaches at room temperature (25 °C), after 5 min of cold stress (4 °C), and after 5 min of hot stress (42 °C). We found that the time-varying Esingle curves were very close to the time-varying Emultiple curves. Meanwhile, there was a regression line (Esingle = 0.019 + 0.91 Emultiple, standard error of the estimate (SEE) = 0.0295, p < 0.0001) with a high correlation coefficient (0.995) between Esingle and Emultiple. Furthermore, from the Bland-Altman plot, good precision and agreement between the two approaches were demonstrated. In summary, the proposed approach with a single-frequency vibrator and a force sensor showed its feasibility for measuring time-varying wall elastances.

17.
Medicine (Baltimore) ; 99(45): e22017, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157910

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 viral infection resulting in corona virus disease 2019 (COVID-19) disease has recently been designated by the World Health Organization as a global pandemic. Some doctors are using convalescent plasma (CP) therapies to treat COVID-19 patients. However, whether CP therapy is effective for children with COVID-19 remains controversial. Therefore, this study further explores the effectiveness and safety of human coronavirus immune CP in the treatment of COVID-19 in children. METHODS: Comprehensively search the electronic databases such as the Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, and WanFang, and collect relevant documents. We will also look for other sources. All document sources will not be restricted by language and publication status. Two researchers will independently conduct research selection, data extraction and research quality assessment. RevMan 5.3 was used for statistical analysis. RESULTS: This study will provide high-quality comprehensive evidence for the effectiveness and safety of human coronavirus immuno CP in the treatment of COVID-19 in children CONCLUSIONS:: The results of this study will provide the basis for the effectiveness and safety of human coronavirus immuno CP treatment of COVID-19 in children. PROSPERO REGISTRATION NUMBER: CRD42020199410.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Betacoronavirus , Criança , Criança Hospitalizada , Humanos , Imunização Passiva , Metanálise como Assunto , Pandemias , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
18.
PLoS One ; 15(11): e0242013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166371

RESUMO

BACKGROUND: Pneumothorax can lead to a life-threatening emergency. The experienced radiologists can offer precise diagnosis according to the chest radiographs. The localization of the pneumothorax lesions will help to quickly diagnose, which will be benefit for the patients in the underdevelopment areas lack of the experienced radiologists. In recent years, with the development of large neural network architectures and medical imaging datasets, deep learning methods have become a methodology of choice for analyzing medical images. The objective of this study was to the construct convolutional neural networks to localize the pneumothorax lesions in chest radiographs. METHODS AND FINDINGS: We developed a convolutional neural network, called CheXLocNet, for the segmentation of pneumothorax lesions. The SIIM-ACR Pneumothorax Segmentation dataset was used to train and validate CheXLocNets. The training dataset contained 2079 radiographs with the annotated lesion areas. We trained six CheXLocNets with various hyperparameters. Another 300 annotated radiographs were used to select parameters of these CheXLocNets as the validation set. We determined the optimal parameters by the AP50 (average precision at the intersection over union (IoU) equal to 0.50), a segmentation evaluation metric used by several well-known competitions. Then CheXLocNets were evaluated by a test set (1082 normal radiographs and 290 disease radiographs), based on the classification metrics: area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive predictive value (PPV); segmentation metrics: IoU and Dice score. For the classification, CheXLocNet with best sensitivity produced an AUC of 0.87, sensitivity of 0.78 (95% CI 0.73-0.83), and specificity of 0.78 (95% CI 0.76-0.81). CheXLocNet with best specificity produced an AUC of 0.79, sensitivity of 0.46 (95% CI 0.40-0.52), and specificity of 0.92 (95% CI 0.90-0.94). For the segmentation, CheXLocNet with best sensitivity produced an IoU of 0.69 and Dice score of 0.72. CheXLocNet with best specificity produced an IoU of 0.77 and Dice score of 0.79. We combined them to form an ensemble CheXLocNet. The ensemble CheXLocNet produced an IoU of 0.81 and Dice score of 0.82. Our CheXLocNet succeeded in automatically detecting pneumothorax lesions, without any human guidance. CONCLUSIONS: In this study, we proposed a deep learning network, called, CheXLocNet, for the automatic segmentation of chest radiographs to detect pneumothorax. Our CheXLocNets generated accurate classification results and high-quality segmentation masks for the pneumothorax at the same time. This technology has the potential to improve healthcare delivery and increase access to chest radiograph expertise for the detection of diseases. Furthermore, the segmentation results can offer comprehensive geometric information of lesions, which can benefit monitoring the sequential development of lesions with high accuracy. Thus, CheXLocNets can be further extended to be a reliable clinical decision support tool. Although we used transfer learning in training CheXLocNet, the parameters of CheXLocNet was still large for the radiograph dataset. Further work is necessary to prune CheXLocNet suitable for the radiograph dataset.

19.
Cell Death Dis ; 11(11): 971, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184264

RESUMO

Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/ß-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/ß-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.

20.
Dis Markers ; 2020: 8860445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204366

RESUMO

The proinflammatory chemokine interleukin-32 is related to various diseases, including cancer. However, it has never been associated with bladder cancer (BC). To detect whether there is a relationship between the IL-32 gene polymorphisms (rs12934561 C/T and rs28372698 T/A) and BC, the study enrolled 170 non-muscle-invasive bladder cancer (NMIBC) patients, 151 muscle-invasive bladder cancer (MIBC) patients, and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the IL-32 single-nucleotide polymorphism (SNP) genotyping. Statistical analysis was performed using SNPstats online analysis software and SPSS software. Our data revealed that the CC homozygous genotype of rs12934561 in BC patients was significantly higher than that in controls (P = 0.03, OR = 1.47, 95%CI = 1.04-2.08), and the percentage of TC genotype carriers was relatively less than that of controls (P = 0.001, OR = 0.61, 95%CI = 0.45-0.82). Furthermore, the TT homozygous genotype of rs28372698 was associated with a significantly lower overall survival rate in MIBC patients (P = 0.028, OR = 2.77, 95%CI = 1.11-6.90). The IL-32 gene polymorphism rs12934561 might be associated with increased BC risk, and the rs28372698 might participate in the prognosis of BC patients. Therefore, they could be potential forecasting factors for the prognosis of MIBC patients.

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