RESUMEN
An important reason of cancer proliferation is the change in DNA methylation patterns, characterized by the localized hypermethylation of the promoters of tumor-suppressor genes together with an overall decrease in the level of 5-methylcytosine (5mC). Therefore, identifying the 5mC sites in the promoters is a critical step towards further understanding the diverse functions of DNA methylation in genetic diseases such as cancers and aging. However, most wet-lab experimental techniques are often time consuming and laborious for detecting 5mC sites. In this study, we proposed a deep learning-based approach, called BiLSTM-5mC, for accurately identifying 5mC sites in genome-wide DNA promoters. First, we randomly divided the negative samples into 11 subsets of equal size, one of which can form the balance subset by combining with the positive samples in the same amount. Then, two types of feature vectors encoded by the one-hot method, and the nucleotide property and frequency (NPF) methods were fed into a bidirectional long short-term memory (BiLSTM) network and a full connection layer to train the 22 submodels. Finally, the outputs of these models were integrated to predict 5mC sites by using the majority vote strategy. Our experimental results demonstrated that BiLSTM-5mC outperformed existing methods based on the same independent dataset.
Asunto(s)
5-Metilcitosina/análisis , Envejecimiento/metabolismo , ADN/genética , Aprendizaje Profundo , Neoplasias/metabolismo , 5-Metilcitosina/metabolismo , Envejecimiento/genética , Metilación de ADN , Humanos , Memoria a Corto Plazo , Neoplasias/genética , Regiones Promotoras Genéticas/genéticaRESUMEN
The increasing incidence of antibiotic resistance has forced the development of unique antimicrobials with novel multitargeting mechanisms to combat infectious diseases caused by multidrug-resistant pathogens. Structurally unique indolylcyanoethylenyl sulfonylanilines (ISs) were exploited as novel promising antibacterial agents to confront stubborn drug resistance. Some prepared ISs possessed favorable bacteriostatic action towards the tested bacteria. Especially, hydroxyethyl IS 14a exerted 8-fold more potent inhibitory efficacy against multidrug-resistant A. baumannii and E. coli 25922 with the low MIC of 0.5 µg/mL than norfloxacin, and showed low cell toxicity and rapid bactericidal property. Moreover, this compound also possessed obvious effect of eradicating bacterial biofilm, which could effectually relieve the development of drug resistance. A preliminary assessment of the antibacterial mechanism indicated that compound 14a could disintegrate membrane integrity leading to the leakage of intracellular protein, inactivation of lactate dehydrogenase and metabolism inhibition. Hydroxyethyl IS 14a mediated the accumulation of excess reactive oxygen species, which further contributed to reducing glutathione, resulting in oxidative damage to bacteria. Furthermore, IS 14a could intercalate into DNA to hinder the biological function of DNA. Quantum chemical study disclosed that IS 14a with the lowest energy gap was conducive to displaying high bioactivity. These findings demonstrated that hydroxyethyl IS 14a as a prospective antimicrobial candidate for combating A. baumannii and E. coli 25922 would be a promising starting point.
Asunto(s)
Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Estudios Prospectivos , Norfloxacino , BiopelículasRESUMEN
Cancer of unknown primary site (CUP) is a heterogeneous group of cancers whose tissue of origin remains unknown after detailed investigation by conventional clinical methods. The number of CUP accounts for roughly 3%-5% of all human malignancies. CUP patients are usually treated with broad-spectrum chemotherapy, which often leads to a poor prognosis. Recent studies suggest that the treatment targeting the primary lesion of CUP will significantly improve the prognosis of the patient. Therefore, it is urgent to develop an efficient method to accurately detect tissue of origin of CUP in clinical cancer research. In this work, we developed a novel framework that uses Extreme Gradient Boosting (XGBoost) to trace the primary site of CUP based on microarray-based gene expression data. First, we downloaded the microarray-based gene expression profiles of 59,385 genes for 57,08 samples from The Cancer Genome Atlas (TCGA) and 6,364 genes for 3,101 samples from the Gene Expression Omnibus (GEO). Both data were divided into training and independent testing data with a ratio of 4:1. Then, we obtained in the training data 200 and 290 genes from TCGA and the GEO datasets, respectively, to train XGBoost models for the identification of the primary site of CUP. The overall 5-fold cross-validation accuracies of our methods were 96.9% and 95.3% on TCGA and GEO training datasets, respectively. Meanwhile, the macro-precision for the independent dataset reached 96.75% and 98.8% on, respectively, TCGA and GEO. Experimental results demonstrated that the XGBoost framework not only can reduce the cost of clinical cancer traceability but also has high efficiency, which might be useful in clinical usage.
RESUMEN
Identification of bacterial type III secreted effectors (T3SEs) has become a popular research topic in the field of bioinformatics due to its crucial role in understanding host-pathogen interaction and developing better therapeutic targets against the pathogens. However, the recognition of all effector proteins by using traditional experimental approaches is often time-consuming and laborious. Therefore, development of computational methods to accurately predict putative novel effectors is important in reducing the number of biological experiments for validation. In this study, we proposed a method, called iT3SE-PX, to identify T3SEs solely based on protein sequences. First, three kinds of features were extracted from the position-specific scoring matrix (PSSM) profiles to help train a machine learning (ML) model. Then, the extreme gradient boosting (XGBoost) algorithm was performed to rank these features based on their classification ability. Finally, the optimal features were selected as inputs to a support vector machine (SVM) classifier to predict T3SEs. Based on the two benchmark datasets, we conducted a 100-time randomized 5-fold cross validation (CV) and an independent test, respectively. The experimental results demonstrated that the proposed method achieved superior performance compared to most of the existing methods and could serve as a useful tool for identifying putative T3SEs, given only the sequence information.
Asunto(s)
Posición Específica de Matrices de Puntuación , Máquina de Vectores de Soporte , Sistemas de Secreción Tipo III/clasificación , Sistemas de Secreción Tipo III/genética , Algoritmos , Secuencia de Aminoácidos , Biología Computacional , Bases de Datos de Proteínas , Aprendizaje AutomáticoRESUMEN
PURPOSE: This study aimed to investigate if preoperative assessments of multiparametric magnetic resonance imaging (mpMRI) and Magnetic resonance imaging /ultrasound (MRI/US) fusion-guided prostate biopsy could be used to guide focal therapy for prostate cancer. MATERIALS AND METHODS: A total of 101 prostate cancer patients undergoing radical prostatectomy were included. Preoperative findings included mpMRI and MRI/US fusion-guided prostate biopsy, while postoperative whole mount pathology was based on surgical specimen. RESULTS: Of the 101 patients preoperatively diagnosed with a unilateral tumor, postoperative whole mount pathology showed 73.27% were bilateral tumors, and 71.62% of bilateral lesions were clinically significant. Comparison between preoperative and postoperative findings, the correct rate of preoperative mpMRI on the lesion side (left or right) was only 20.79%. As for the Gleason score, the correct rate of preoperative MRI/US fusion-guided prostate pathology was 67.33%. Judging from postoperative whole mount pathology, 47.52% of patients had a unilateral clinically significant tumor, which is an indication for focal therapy. CONCLUSION: Preoperative examinations of mpMRI and MRI/US fusion-guided prostate biopsy cannot be used to guide focal therapy for prostate cancer.
Asunto(s)
Biopsia Guiada por Imagen/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Masculino , Periodo Preoperatorio , Estudios RetrospectivosRESUMEN
In February 2020, a novel coronavirus (SARS-COV2) broke out in Wuhan city of China. The Chinese government decisively imposed nationwide confinement. This study comprised a structured, online questionnaire, based on 40 items inquiring about socio-demographic information and anthropometric data (reporting weight and height), as well as changes in food intake, physical activity, and sleep during the COVID-19 outbreak. Questionnaires were distributed to residents of Jiangsu and other provinces from 29 March to 5 April. A total of 889 respondents were included, aged between 16 and 70 years (61% females). There was a significant increase in total food intake by 9.8% and a slight increase by 29.2% of respondents, and a significant decrease in physical activity by 31.5% and a slight decrease by 23.4% of respondents, especially in snacks and drinks, and outdoor activities. The rate of weight gain in the total population was 30.6% and the average weight gain was 0.5 ± 2.8 kg. The main factors contributing to weight gain were increased food intake and reduced physical activity. Additionally, normal-weight people were more likely to gain weight than people with overweight/obesity during the COVID-19 confinement. This study provided a good warning and educational reference value on lifestyle changes during the COVID-19 confinement.
Asunto(s)
COVID-19/prevención & control , Estilo de Vida , Cuarentena , Aumento de Peso , Adolescente , Adulto , Anciano , China/epidemiología , Ejercicio Físico , Conducta Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , ARN Viral , Encuestas y Cuestionarios , Adulto JovenRESUMEN
PURPOSE: Radical prostatectomy (RP) is a common treatment for prostate cancer, but a fraction of patients may experience PSA recurrence after surgery, manifesting as an elevation in prostate specific antigen (PSA). Vast literature has reported different prognostic factors for PSA recurrence without reaching a consensus. This retrospective study investigated the efficacy of a new indicator in predicting PSA recurrence in patients after RP. PATIENTS AND METHODS: From October 2000 to December 2015, 102 PCa patients who underwent laparoscopic prostatectomy in the Urology Department of Peking Union Medical College Hospital were analyzed. We calculated PSApostd3/PSApre, defined as the ratio of the PSA on day 3 postop as the numerator and the pre-operative PSA as the denominator, in these patients to represent PSA decrement after surgery, and investigated its relationship with PSA recurrence during follow-up. RESULTS: The receiver operating characteristic (ROC) curve of PSApostd3/PSApre derived a cut-off at 0.453 (sensitivity=0.704, specificity=0.853, P<0.0001), suggesting an increased risk of PSA recurrence in patients whose PSA on day 3 postop did not decrease to approximately half of their preoperative levels. Among several factors, PSApostd3/PSApre (P<0.0001), pathological T stage (P=0.042) and Gleason Grade (P=0.021) were determined to be significantly associated with PSA recurrence by Fisher's exact test, while only PSApostd3/PSApre (P<0.001) was significantly related to PSA recurrence-free survival (PRFS) by multivariate logistic regression analysis. CONCLUSION: These results imply that PSApostd3/PSApre could provide substantial information for PSA recurrence prediction in patients after RP.
RESUMEN
To compare the accuracy of magnetic resonance-guided prostate biopsy (MR-GPB) and template-guided transperineal prostate saturation biopsy (TTPSB).A total of 219 patients with elevated prostate-specific antigen, abnormal digital rectal examination or ultrasound findings were enrolled. All patients underwent multiparametric magnetic resonance image (mpMRI). Patients with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 to 5 underwent MR-GPB using 2 to 5 biopsy cores and then immediately underwent an 11-region TTPSB. Patients with a PI-RADS score of 1 to 2 underwent TTPSB alone. We compared the detection rates for any cancer, clinically significant prostate cancer (csPCA), and the spatial distribution of missed csPCA lesions.Among the 219 cases, 66 (30.1%) had a PI-RADS score of 1 to 2 on mpMRI. The detection rate of TTPSB in these patients was 9.1% (6/66). In total, detection rates for any cancer and csPCA were 48.9% (107/219) and 42.9% (94/219), respectively. Detection rates for any cancer (TTPSB 87/219, 39.7%; MR-GPB76/219, 34.7%, Pâ=â.161) and csPCA (TTPSB 76/219, 34.7%; MR-GPB 72/219, 32.9%, Pâ=â.636) did not significantly differ between the 2 groups. The csPCA lesions missed by MR-GPB were most commonly located on the left (8.5%, 8/94) and right (9.6%, 9/94) sides of the urethra.MR-GPB can reduce the rate of unnecessary prostate biopsies by approximately 30% and exhibits an efficacy comparable to TTPSB for the detection of any cancer and csPCA. Nevertheless, approximately 1/4 of csPCAs were missed by MR-GPB and were most commonly located on both sides of the urethra.
Asunto(s)
Detección Precoz del Cáncer/estadística & datos numéricos , Biopsia Guiada por Imagen/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Detección Precoz del Cáncer/métodos , Humanos , Biopsia Guiada por Imagen/métodos , Masculino , Persona de Mediana Edad , Perineo/patología , Próstata/diagnóstico por imagen , Próstata/patología , Uretra/patologíaRESUMEN
In the present work, mono-disperse and uniform orthorhombic lutetium fluoride (LuF3) nanocrystals with an average size of about 35 nm have been successfully synthesized by a simple ionothermal method without any template. The infrared (IR) to visible up-conversion (UC) photoluminescence of LuF3 doped with Yb3+, Tm3+, and Ho3+ under 980 nm excitation was systemically studied. The intensity of near infrared (NIR) to visible up-conversion emission of Tm3+ was improved efficiently by adding Yb3+ and Ho3+ in LuF3, especially for the broad NIR emission band located at 812 nm. Meanwhile, compared to the Yb3+ and Tm3+ co-doped LuF3, the ratio of red to green emission in the Yb3+, TmS+, and HoS+ co-doped LuF3 changed greatly, and a bright yellowish-green emission was observed under 980 nm laser excitation. It shows that Yb3+, Tm3+ and Ho3+ co-doped LuF3 nanocrystals provided a potential application in vitro and in vivo bio-imaging, color displays and optical storage.
RESUMEN
A series of liquid-crystalline polysiloxanes synthesized by cholest-5-en-3-ol (3beta)-10-undecenoate and 4'-octanoyloxy-biphenyl-4-yl 4-allyloxy-3-sulfo-benzoate were prepared in a one-step reaction with sulfonic acid group contents ranging between 0 and 2.73 wt %. All the polymers displayed smectic mesophases with a large temperature range for the mesophases. With an increase of sulfonic acid containing mesogens in the polymers, the temperature of the glass transition did not change greatly, while the temperature of the clear point decreased. The hydrogen-bonding mesogen aggregates in the domains disturb the liquid-crystalline molecular mobility and orientation, leading to a decrease in temperature from the mesophase to the isotropic transition. Unlike the polymers containing lower sulfonic acid mesogens, some polymers showed a dendritic texture of the SmB* phase, indicating that the sulfonic mesogens enhanced the rigid moieties of the supermolecular structure of the liquid-crystalline phases. All the polymers displayed sharp and strong peaks at low angles around 2theta approximately 2.6 degrees and broad peaks at wide angles around 2theta approximately 17 degrees in X-ray measurements. The intensity of the strong peak at low angles in the X-ray profiles decreased with an increase of sulfonic acid mesogens in the polymer systems.