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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 166-169, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829686

RESUMO

The incidence of gastric cancer is the highest among all kinds of malignant tumors in China. Because gastric cancer is very hard to identify in its early stage, the early diagnosis rate of gastric cancer in China is relatively low. At present, the pathological diagnosis of gastric cancer mainly depends on the diagnosis of pathologists. However, the gradual improvement of people's living standards and the growing demand for medical and health care have exacerbated the shortage of medical resources, which has become a even more serious problem. Therefore, there is an urgent need for new technologies to help deal with this challenge. In recent years, with the rapid development of artificial intelligence (AI) and digital pathology, AI-aided pathological diagnosis based on convolutional neural network (CNN) as the core technology is showing promises for improving the diagnostic efficiency of gastric cancer. It is also of great significance for the early diagnosis and treatment of the disease and the reduction of its high incidence and mortality. We herein summarize the application and progress of deep-learning CNN in pathological diagnosis of gastric cancer, as well as the existing problems and prospects of future development.


Assuntos
Neoplasias Gástricas , Inteligência Artificial , China/epidemiologia , Humanos , Redes Neurais de Computação , Neoplasias Gástricas/diagnóstico
2.
Artigo em Inglês | MEDLINE | ID: mdl-33760739

RESUMO

Hypertension (HT), or high blood pressure is one of the most common and main causes in cardiovascular diseases, which is also related to a series of detrimental diseases in humans. Deficiencies in effective treatment in HT are often associated with a series of diseases including multi-infarct dementia, amputation, and renal failure. Therefore, identifying anti-hypertension peptides has the vital realistic significance. Although many bioactive peptides have been developed to reduce blood pressure, they are time-consuming and laborious. In views of the obstacles of the intrinsic methods in antihypertensive peptide (AHTP) classification, computational methods are suggested as a supplement to identify AHTPs. In this study, we develop a comprehensive feature rep-resentation algorithm based on pretrained model and convolutional neural network and apply the deep ensemble model to construct the prediction model. The new predictor is used to identify AHTPs in benchmark and independent datasets. It has been shown in the independent test set that the performance is better than the recent methods. Comparative results indicate that our model can shed some light on hypertension therapy and gains more insights of classifying AHTPs. The implements and codes can be found in https://github.com/yuanying566/AHPred-DE.

3.
Cardiovasc Ultrasound ; 19(1): 16, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663519

RESUMO

BACKGROUND: Studies on the management of functional tricuspid regurgitation (TR) during mitral valve operations have drawn inconsistent conclusions. This study was designed to compare the treatment strategy of concomitant tricuspid annuloplasty (TAP) against isolated mitral valve replacement (MVR) in rheumatic mitral valve disease patients, and to assess the effect of concomitant TAP on postoperative right ventricular (RV) remodeling and function. METHODS: One hundred-seventy patients with rheumatic mitral valve disease receiving MVR were categorized into TAP group (n = 124) and non-TAP group (n = 46). Clinical and echocardiographic data were collected preoperatively and at 1-year follow-up. Three-dimensional echocardiographic indices of RV geometry and function were analyzed. RESULTS: At baseline, concomitant TAP group had larger RV end-diastolic volume, more decreased RV ejection fraction and RV longitudinal strain than non-TAP group (all P <  0.001). At 1-year follow-up, TAP group had improved RV geometry and function. While adverse changes were observed in non-TAP group. In analysis of variance, the above indices demonstrated significant interaction with different treatment group (all P <  0.001). In multivariate regression analysis, independent of age and Maze procedure, concomitant TAP was associated with postoperative RV volume reduction (P <  0.001), improvement of RV ejection fraction (P <  0.001), and relieved postoperative functional TR severity (P = 0.025). CONCLUSIONS: Our results suggest that concomitant TAP could improve RV remodeling and function for rheumatic mitral valve disease patients, while those with mild preoperative functional TR who had isolated MVR might experience RV dilation and deterioration of RV function at follow-up. Concomitant surgery for functional TR could be considered for patients undergoing MVR with rheumatic mitral valve disease.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33588722

RESUMO

BACKGROUND: Drug development requires a lot of money and time, and the outcome of the challenge is unknown. So, there is an urgent need for researchers to find a new approach that can reduce costs. Therefore, the identification of drug-target interactions (DTIs) has been a critical step in the early stages of drug discovery. These computational methods aim to narrow the search space for novel DTIs and to elucidate the functional background of drugs. Most of the methods developed so far use binary classification to predict the presence or absence of interactions between the drug and the target. However, it is more informative, but also more challenging, to predict the strength of the binding between a drug and its target. If the strength is not strong enough, such a DTI may not be useful. Hence, the development of methods to predict drug-target affinity (DTA) is of significant importance. METHOD: We have improved the Graph DTA model from a dual-channel model to a triple-channel model. We interpreted the target/protein sequences as time series and extracted their features using the LSTM network. For the drug, we considered both the molecular structure and the local chemical background, retaining the four variant networks used in Graph DTA to extract the topological features of the drug and capturing the local chemical background of the atoms in the drug by using BiGRU. Thus, we obtained the latent features of the target and two latent features of the drug. The connection of these three feature vectors is then input into a 2-layer FC network, and a valuable binding affinity is output. RESULT: We use the Davis and Kiba datasets, using 80% of the data for training and 20% of the data for validation. Our model shows better performance by comparing it with the experimental results of Graph DTA. CONCLUSION: In this paper, we altered the Graph DTA model to predict drug-target affinity. It represents the drug as a graph, and extracts the two-dimensional drug information using a graph convolutional neural network. Simultaneously, the drug and protein targets are represented as a word vector, and the convolutional neural network is used to extract the time series information of the drug and the target. We demonstrate that our improved method has better performance than the original method. In particular, our model has better performance in the evaluation of benchmark databases.

5.
Lancet Digit Health ; 3(2): e88-e97, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33509389

RESUMO

BACKGROUND: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. METHODS: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. FINDINGS: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. INTERPRETATION: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. FUNDING: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.


Assuntos
Algoritmos , Simulação por Computador , Aprendizado Profundo , Doenças do Sistema Digestório/diagnóstico , Olho , Programas de Rastreamento/métodos , Modelos Biológicos , Adulto , Área Sob a Curva , China , Túnica Conjuntiva/diagnóstico por imagem , Doenças do Sistema Digestório/complicações , Olho/diagnóstico por imagem , Fundo de Olho , Humanos , Iris/diagnóstico por imagem , Fígado , Pessoa de Meia-Idade , Fotografação/métodos , Estudos Prospectivos , Curva ROC , Esclera/diagnóstico por imagem , Microscopia com Lâmpada de Fenda/métodos
6.
Sci Total Environ ; 753: 141949, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32891999

RESUMO

Bisphenol S (BPS) is the major substitute for the production of bisphenol A (BPA)-free products and detected in both food and environment. Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted, the potential influence of BPS is not fully understood. Herein, a non-targeted lipidomic study was performed to explore BPA/BPS exposure actions using the 3T3-L1 preadipocyte differentiation model, and revealed the comprehensive lipidome disturbance induced by either BPA or BPS exposure at different doses of 0.01, 1 and 100 µM. BPA was more potent than BPS in disturbance of lipid metabolism. A considerable similarity of BPS exposure to BPA was discovered. The key lipid remodeling in response to exposure was found to involve the cardiolipins, phosphatidylglycerols and fatty acids metabolic pathways, providing novel clues of potential mechanism in which both BPA and BPS exposure could be associated with increased risk of insulin resistance. Our study supplies the perspective into the lipidome response to environmental stress induced by BPA/BPS, and shows that BPA-free products are not necessarily safer. Substitution of BPA by its structural analog BPS should be therefore performed with caution.


Assuntos
Compostos Benzidrílicos , Lipidômica , Animais , Compostos Benzidrílicos/toxicidade , Camundongos , Fenóis/toxicidade , Sulfonas
7.
Aging (Albany NY) ; 122020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33203802

RESUMO

Increased vascular endothelial permeability can disrupt vascular barrier function and further lead to multiple human diseases. Our previous reports indicated that particulate matter 2.5 (PM2.5) can enhance the permeability of vascular endothelial cells. However, the regulatory mechanism was not comprehensively demonstrated. Therefore, this work elucidated this mechanism by demonstrating that PM2.5 can increase the permeability of HUVECs by inhibiting the expression of Hickson compact group 18 (HCG18). Moreover, we demonstrated that lncRNA HCG18 functioned as a ceRNA for miR-21-5p and led to the derepression of its target SOX7, which could further transcriptionally activate the expression of VE-cadherin to regulate the permeability of HUVECs. In this study, we provide evidence that HCG18/miR-21-5p/SOX7/VE-cadherin signaling is involved in PM2.5-induced vascular endothelial barrier dysfunction.

8.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33034616

RESUMO

BACKGROUND: Metastasis is a major obstacle in treatment of cervical cancer, and long non-coding RNA (lncRNA) mediated regulatory effect on associated genes expression is found to be involved in metastasis. However, its mechanisms have not been fully elucidated. MATERIALS AND METHODS: Specimens from patients with cervical cancer metastasis and non-metastasis were used to screen out candidate non-coding RNAs (ncRNAs) and possible downstream targets. And then, effects were determined in vitro and in vivo through knockdown and overexpression techniques. RESULTS: LINC00636 was significantly higher in serum and solid tumor cells of metastatic cervical cancer patients than non-metastatic patients. And knockdown of LINC00636 significantly suppressed invasion, proliferation of cervical cancer cells. NM23 expression was negatively regulated by LINC00636 and it mediated anti-tumor effects was partially blocked by overexpression of LINC00636. CONCLUSION: LINC00636 might promote metastasis of cervical cancer cells through inhibiting NM23 expression.

9.
Aging (Albany NY) ; 12(19): 18878-18888, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031060

RESUMO

In this retrospective study we assessed the efficacy and safety of tocilizumab in patients with critical or severe coronavirus disease 2019 (COVID-19). We enrolled 181 patients admitted to Huoshenshan Hospital (Wuhan, China) with confirmed COVID-19 between January 2020 and February 2020. Ninety-two patients were treated with tocilizumab, and 89 patients were treated conventionally. We analyzed the clinical manifestations, changes in CT scan images, and laboratory tests before and after tocilizumab treatment, and compared these results with the conventionally treated group. A significant reduction in the level of C-reactive protein was observed 1 week after tocilizumab administration. In some cases this meant the end of the IL-6-related cytokine storm. In addition, tocilizumab relieved fever, cough, and shortness of breath with no reported adverse drug reactions. These findings suggest tocilizumab improves clinical outcomes and is effective for treatment of patients with critical or severe COVID-19. However, future clinical trials are needed to better understand the impact of tocilizumab interference with IL-6 and provide a therapeutic strategy for treatment of COVID-19.

10.
J Nat Prod ; 83(11): 3338-3346, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33095987

RESUMO

4-Hydroxy pyridones are a class of fungi-derived polyketide-nonribosomal peptide products featuring a core of 4-hydroxy-2-pyridone which have a wide range of biological activities. Genome mining of in-house strains using polyketide synthase-nonribosomal peptide synthase as a query identified an endophyte Tolypocladium sp. 49Y, which possesses a potential 4-hydroxy pyridone biosynthetic gene cluster. Heterologous expression in Aspergillus oryzae NSAR1 revealed that this gene cluster is functional and able to produce a rare type of 4-hydroxy pyridones called tolypyridones (compounds 3 and 4). Tolypocladium sp. 49Y was grown in a variety of media which led to the isolation of six 4-hydroxy pyridones (5-10) and one pyrrolidone (11) from a rice culture, and compounds 3 and 9 showed antifungal activity. These latter compounds are different from those obtained by heterologous expression. This study shows that both heterologous expression and cultivation of the native host are complementary approaches to discover new natural products.

11.
Front Neurol ; 11: 693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849184

RESUMO

There are landmarks on the course of the anterior choroidal artery (AChoA), such as the original point (OP) and the plexal point (PP), as documented in previous articles. In these previous articles, the AChoA was the terminal branch of the internal carotid artery (ICA), which had two segments throughout its course. The first cisternal segment began from the origin and ended at the point where the artery reached the choroidal fissure (the PP). The second segment consisted of one or more branches, which passed through the choroidal fissure and entered the choroid plexus. However, we found another angiographic landmark, named the most external point (MEP), along the course of the AChoA in the anteroposterior (AP) view. There was a sharp turn at the outermost limit of the course of the AChoA, and then the AChoA progressed inward and upward. We defined the outermost limit as the MEP of the AChoA. This study describes two rare cases of distal AChoA aneurysms associated with arteriovenous malformation (AVM) and Moyamoya disease that developed intraventricular hemorrhage, and we used the parent artery occlusion (PAO) technique to embolize the distal AChoA lesions at the MEP. The patients recovered well without any neurological complications.

12.
J Med Chem ; 63(21): 12403-12428, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32659083

RESUMO

Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interest of pharmaceutical chemists and is expected to bring new hope for AML therapy. In this review, we specifically highlighted FLT3 mediated JAK/STAT, RAS/MAPK, and PI3K/AKT/mTOR signaling. The structural properties and biological activities of representative FLT3 inhibitors reported from 2014 to the present were also summarized. In addition, the major challenges in the current advance of novel FLT3 inhibitors were further analyzed, with the aim to guide future drug discovery.

13.
J Ethnopharmacol ; 258: 112932, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32376368

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has been widely used as an approach worldwide. Chinese Medicines (CMs) had been used to treat and prevent viral infection pneumonia diseases for thousands of years and had accumulated a large number of clinical experiences and effective prescriptions. AIM OF THE STUDY: This research aimed to systematically excavate the classical prescriptions of Chinese Medicine (CM), which have been used to prevent and treat Pestilence (Wenbing, Wenyi, Shiyi or Yibing) for long history in China, to obtain the potential prescriptions and ingredients to alternatively treat COVID-19. MATERIALS AND METHODS: We developed the screening system based on data mining, molecular docking and network pharmacology. Data mining and association network were used to mine the high-frequency herbs and formulas from ancient prescriptions. Virtual screening for the effective components of high frequency CMs and compatibility Chinese Medicine was explored by a molecular docking approach. Furthermore, network pharmacology method was used to preliminarily uncover the molecule mechanism. RESULTS: 574 prescriptions were obtained from 96,606 classical prescriptions with the key words to treat "Warm diseases (Wenbing)", "Pestilence (Wenyi or Yibing)" or "Epidemic diseases (Shiyi)". Meanwhile, 40 kinds of CMs, 36 CMs-pairs, 6 triple-CMs-groups existed with high frequency among the 574 prescriptions. Additionally, the key targets of SARS-COV-2, namely 3CL hydrolase (Mpro) and angiotensin-converting enzyme 2(ACE2), were used to dock the main ingredients from the 40 kinds by the LigandFitDock method. A total of 66 compounds components with higher frequency were docked with the COVID-19 targets, which were distributed in 26 kinds of CMs, among which Gancao (Glycyrrhizae Radix Et Rhizoma), HuangQin (Scutellariae Radix), Dahuang (Rhei Radix Et Rhizome) and Chaihu (Bupleuri Radix) contain more potential compounds. Network pharmacology results showed that Gancao (Glycyrrhizae Radix Et Rhizoma) and HuangQin (Scutellariae Radix) CMs-pairs could also interact with the targets involving in immune and inflammation diseases. CONCLUSIONS: These results we obtained probably provided potential candidate CMs formulas or active ingredients to overcome COVID-19. Prospectively, animal experiment and rigorous clinic studies are needed to confirm the potential preventive and treat effect of these CMs and compounds.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/virologia , Mineração de Dados , Humanos , Modelos Moleculares , Pandemias , Extratos Vegetais , Pneumonia Viral/virologia , Conformação Proteica , Proteínas Virais
14.
Biomark Med ; 14(6): 441-450, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32270697

RESUMO

Aim: The present study aimed to investigate the role of TAB2 gene polymorphisms in dilated cardiomyopathy (DCM) susceptibility and prognosis in a Chinese population. Materials & methods: A total of 343 DCM patients and 451 controls were enrolled and had their blood genotyped. Survival analysis was evaluated with Kaplan-Meier curves and Cox regression analysis. Results: G carriers (AG/GG) and AG genotype of rs237028 had a higher DCM susceptibility as well as a worse DCM prognosis. Additionally, C carriers (CT/CC) of rs652921 and G carriers (TG/GG) of rs521845 had a higher DCM risk and CC homozygote of rs652921 had a worse DCM prognosis. These associations were still significant after adjustment for the Bonferroni correction. Conclusion: TAB2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese population.

15.
Medicine (Baltimore) ; 99(9): e19115, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118714

RESUMO

BACKGROUND: Dysphagia is one of the major post-stroke complications that can severely damage a patient's quality of life. An increasing number of studies have demonstrated that many kinds of nonpharmacological treatments can be used for post-stroke dysphagia. However, there is not enough evidence evaluating the effectiveness and safety of these interventions. This study will conduct a systematic review, and Bayesian network meta-analysis, of nonpharmacological treatments in order to provide evidence for a future study investigating more options for post-stroke dysphagia. METHODS: Randomized controlled trials (RCTs) of adult patients aged >18 years old who meet the criteria for a diagnosis of post-stroke dysphagia will be included, regardless of gender, nationality, or education level. Four Chinese databases (CNKI, SinoMed, Wanfang Database, and the Chinese Scientific Journal Database) and four English databases (Web of Science, MEDLINE, Embase, and the Cochrane Library) will be searched. Two independent reviewers will evaluate the title summary for each RCT. Disagreements will be discussed with a third commentator. Standard pairwise meta-analysis, including heterogeneity analysis, subgroup analysis, and sensitivity analysis, will be performed using the RevMan 5.3 software, and the risk of bias assessment will be conducted based on the methodological quality of the included trials recommended by the Cochrane Handbook 5.1. The Bayesian network meta-analysis will be performed using R-3.3.2 software. The quality evaluation of this study will be completed using the World Health Organization's Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: This study will summarize all the selected trials aimed at estimating the effectiveness, as well as safety, of applying nonpharmacological treatments to post-stroke dysphagia. CONCLUSION: This systematic review will provide evidence to assess the validity and safety of applying different types of nonpharmacological treatments for post-stroke dysphagia, which may provide clinicians with more choices in the treatment of this disease. PROSPERO REGISTRATION NUMBER: CRD42019119368.


Assuntos
Transtornos de Deglutição/terapia , Modalidades de Fisioterapia , Acidente Vascular Cerebral/complicações , Transtornos de Deglutição/etiologia , Humanos , Revisões Sistemáticas como Assunto
17.
Eur J Med Chem ; 189: 112038, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31945667

RESUMO

Bufadienolides are a type of natural cardiac steroids and originally isolated from the Traditional Chinese Medicine Chan'Su, they have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy with potent anti-tumor activities. Due to their unique molecular structures with unsaturated six-membered lactones attached to the steroid core, bufadienolides have received great attention in the synthetic organic community. This review presents total synthetic efforts to some representative bufadienolides, chemical modification of bufadienolides will also be given to discuss their structure-activity relationship in anti-tumor.


Assuntos
Bufanolídeos/síntese química , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
18.
ACS Chem Biol ; 15(1): 44-51, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31860257

RESUMO

Fusidane-type antibiotics are a group of triterpenoid antibiotics. They include helvolic acid, fusidic acid, and cephalosporin P1, among which fusidic acid has been used clinically. We have recently elucidated the biosynthesis of helvolic acid and fusidic acid, which share an early biosynthetic route involving six conserved enzymes. Here, we report two separate gene clusters for cephalosporin P1 biosynthesis. One consists of the six conserved genes, and the other contains three genes encoding a P450 enzyme (CepB4), an acetyltransferase (CepD2), and a short-chain dehydrogenase/reductase (CepC2). Introduction of these three genes into Aspergillus oryzae, which harbors the six conserved genes, produced cephalosporin P1. Stepwise introduction revealed that CepB4 not only catalyzes stereoselective dual oxidation of C6 and C7, but also monooxygenation of C6 or C7. This led to the generation of five new analogues. Using monohydroxylated products as substrates, we demonstrated that CepD2 specifically acetylates C6-OH, although both C6-OH and C7-OH acetylated analogues have been identified in nature.

19.
Brief Bioinform ; 21(4): 1425-1436, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31612203

RESUMO

Identification of disease-associated circular RNAs (circRNAs) is of critical importance, especially with the dramatic increase in the amount of circRNAs. However, the availability of experimentally validated disease-associated circRNAs is limited, which restricts the development of effective computational methods. To our knowledge, systematic approaches for the prediction of disease-associated circRNAs are still lacking. In this study, we propose the use of deep forests combined with positive-unlabeled learning methods to predict potential disease-related circRNAs. In particular, a heterogeneous biological network involving 17 961 circRNAs, 469 miRNAs, and 248 diseases was constructed, and then 24 meta-path-based topological features were extracted. We applied 5-fold cross-validation on 15 disease data sets to benchmark the proposed approach and other competitive methods and used Recall@k and PRAUC@k to evaluate their performance. In general, our method performed better than the other methods. In addition, the performance of all methods improved with the accumulation of known positive labels. Our results provided a new framework to investigate the associations between circRNA and disease and might improve our understanding of its functions.

20.
Int J Cardiovasc Imaging ; 36(2): 257-268, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31598812

RESUMO

The aim of this study is to analyze the clinical and echocardiographic determinants of functional tricuspid regurgitation (TR) before and after surgical intervention of rheumatic mitral valve disease, with focus on effectiveness of different methods of tricuspid valve annuloplasty (TAP). Three-dimensional echocardiographic images were obtained in 170 patients with mitral valve rheumatic disease before and 1 year after mitral valve replacement, with and without concomitant TAP. Together with standard cardiac chamber quantification, multiplanar reconstruction images of the tricuspid valve (TV) apparatus were analyzed in the septal-lateral and antero-posterior directions, end-diastolic TV annular diameter, TV tenting height and tenting area were measured. By multivariate logistic regression, septal-lateral TV tenting area (p < 0.001) were independently correlated with preoperative FTR severity while postoperative septal-lateral TV annular diameter (p < 0.001) independently determined residual TR at 1-year follow-up. Both ring and suture TAP groups had postoperative reduction of S-L TV diameters, but isolated MVR group had an 11% increase in S-L TV diameters. Compared with TAP of size 26 mm and 28 mm rings group, suture TAP group had more common significant residual TR (29% vs. 3%, p = 0.001). Our study demonstrated that ring annuloplasty could provide effective reduction of the TV annulus and prevent postoperative TR progression, and for rheumatic mitral valve disease patients with mild functional TR, prophylactic TAP concomitant with MVR might be considered to address the postoperative TV annulus dilation.


Assuntos
Anuloplastia da Valva Cardíaca , Ecocardiografia Tridimensional , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/cirurgia , Adulto , Anuloplastia da Valva Cardíaca/efeitos adversos , Anuloplastia da Valva Cardíaca/instrumentação , Progressão da Doença , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/fisiopatologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Cardiopatia Reumática/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
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