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1.
Brief Bioinform ; 23(4)2022 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-35656712

RESUMEN

Multiplexed single-cell proteomes (SCPs) quantification by mass spectrometry greatly improves the SCP coverage. However, it still suffers from a low number of protein identifications and there is much room to boost proteins identification by computational methods. In this study, we present a novel framework DeepSCP, utilizing deep learning to boost SCP coverage. DeepSCP constructs a series of features of peptide-spectrum matches (PSMs) by predicting the retention time based on the multiple SCP sample sets and fragment ion intensities based on deep learning, and predicts PSM labels with an optimized-ensemble learning model. Evaluation of DeepSCP on public and in-house SCP datasets showed superior performances compared with other state-of-the-art methods. DeepSCP identified more confident peptides and proteins by controlling q-value at 0.01 using target-decoy competition method. As a convenient and low-cost computing framework, DeepSCP will help boost single-cell proteome identification and facilitate the future development and application of single-cell proteomics.


Asunto(s)
Aprendizaje Profundo , Proteoma , Péptidos/química , Proteoma/metabolismo , Proteómica/métodos , Espectrometría de Masas en Tándem/métodos
2.
Microb Pathog ; 192: 106717, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38806136

RESUMEN

There are no other bovine coronavirus (BCoV) infection models except calves, which makes efficacy evaluation of vaccines and pathogenic mechanism research of BCoV inconvenient owing to their high value and inconvenient operation. This study aimed to establish a mouse model of BCoV infection. BCoV was used to infect 4-week-old male BALB/c mice and the optimal infection conditions were screened, including the following infection routes: gavage, intraperitoneal injection, and tail vein injection at doses of 1 × 108 TCID50, 2 × 108 TCID50 and 4 × 108 TCID50. Using the optimal infection conditions, BALB/c mice were infected with BCoV, and their body weight, blood routine, inflammatory factors, autopsy, virus distribution, and viral load were measured at 1, 3, 5, and 7 days after infection. The results showed that the optimal conditions for infecting BALB/c mice with BCoV HLJ-325 strain were continuous oral gavage for 3 days with a dose of 4 × 108 TCID50. On the 7th day after infection, there was significant extensive consolidation of the lungs and thinning of the colon wall. Significant inflammation was observed in various organs, especially in the colon and alveoli, where a large number of inflammatory cells infiltrate. Both BCoV Ag and nucleic acid are positive in visceral organs. The viral load in the colon and lungs was significantly higher than that in the other organs (p < 0.001). BCoV-infected mice showed a decreasing trend in body weight starting from day 5, and there was a significant difference compared to the control group on days 6 and 7 (p < 0.001). The total number of white blood cells and lymphocytes began to decrease and was significantly lower than that in the control group 24 h after infection (p < 0.001), and gradually returned to the control level. The cytokine TNF-α, IL-1ß, and IL-6 showed an increasing trend, significantly higher than the control group on day 5 and 7 (p < 0.001). These results indicate that the BCoV HLJ-325 strain can infect BALB/c mice and cause inflammatory reactions and tissue lesions. The most significant effect was observed on the seventh day after infection with a dose of 4 × 108 TCID50 and three consecutive gavages. This study established, for the first time, a BALB/c mouse model of BCoV infection, providing a technical means for evaluating the immune efficacy of BCoV vaccines and studying their pathogenic mechanisms.


Asunto(s)
Infecciones por Coronavirus , Coronavirus Bovino , Modelos Animales de Enfermedad , Pulmón , Ratones Endogámicos BALB C , Carga Viral , Animales , Ratones , Masculino , Pulmón/patología , Pulmón/virología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Bovinos , Susceptibilidad a Enfermedades , Colon/patología , Colon/virología , Interleucina-6/sangre , Interleucina-1beta , Factor de Necrosis Tumoral alfa , Citocinas/metabolismo , Citocinas/sangre , Peso Corporal
3.
Pediatr Nephrol ; 39(5): 1447-1457, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38041747

RESUMEN

BACKGROUND: Split kidney function (SKF) is critical for treatment decision in pediatric patients with hydronephrosis and is commonly measured using renal scintigraphy (RS). Non-contrast-enhanced magnetic resonance urography (NCE-MRU) is increasingly used in clinical practice. This study aimed to investigate the feasibility of using NCE-MRU as an alternative to estimate SKF in pediatric patients with hydronephrosis, compared to RS. METHODS: Seventy-five pediatric patients with hydronephrosis were included in this retrospective study. All patients underwent NCE-MRU and RS within 2 weeks. Kidney parenchyma volume (KPV) and texture analysis parameters were obtained from T2-weighted (T2WI) in NCE-MRU. The calculated split KPV (SKPV) percent and texture analysis parameters percent of left kidney were compared with the RS-determined SKF. RESULTS: SKPV showed a significant positive correlation with SKF (r = 0.88, p < 0.001), while inhomogeneity was negatively correlated with SKF (r = - 0.68, p < 0.001). The uncorrected and corrected prediction models of SKF were established using simple and multiple linear regression. Bland-Altman plots demonstrated good agreement of both predictive models. The residual sum of squares of the corrected prediction model was lower than that of the uncorrected model (0.283 vs. 0.314) but not statistically significant (p = 0.662). Subgroup analysis based on different MR machines showed correlation coefficients of 0.85, 0.95, and 0.94 between SKF and SKPV for three different scanners, respectively (p < 0.05 for all). CONCLUSIONS: NCE-MRU can be used as an alternative method for estimating SKF in pediatric patients with hydronephrosis when comparing with RS. Specifically, SKPV proves to be a simple and universally applicable indicator for predicting SKF.


Asunto(s)
Hidronefrosis , Urografía , Niño , Humanos , Estudios Retrospectivos , Urografía/métodos , Hidronefrosis/diagnóstico por imagen , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Cintigrafía , Espectroscopía de Resonancia Magnética
4.
Plant Cell Rep ; 43(4): 100, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38498220

RESUMEN

KEY MESSAGE: The blast resistance allele of OsBsr-d1 does not exist in most japonica rice varieties of Jilin Province in China. The development of Bsr-d1 knockout mutants via CRISPR/Cas9 enhances broad-spectrum resistance to rice blast in Northeast China. Rice blast is a global disease that has a significant negative impact on rice yield and quality. Due to the complexity and variability of the physiological races of rice blast, controlling rice blast is challenging in agricultural production. Bsr-d1, a negative transcription factor that confers broad-spectrum resistance to rice blast, was identified in the indica rice cultivar Digu; however, its biological function in japonica rice varieties is still unclear. In this study, we analyzed the blast resistance allele of Bsr-d1 in a total of 256 japonica rice varieties from Jilin Province in Northeast China and found that this allele was not present in these varieties. Therefore, we generated Bsr-d1 knockout mutants via the CRISPR/Cas9 system using the japonica rice variety Jigeng88 (JG88) as a recipient variety. Compared with those of the wild-type JG88, the homozygous Bsr-d1 mutant lines KO#1 and KO#2 showed enhanced leaf blast resistance at the seedling stage to several Magnaporthe oryzae (M. oryzae) races collected from Jilin Province in Northeast China. Physiological and biochemical indices revealed that the homozygous mutant lines produced more hydrogen peroxide than did JG88 plants when infected with M. oryzae. Comparative RNA-seq revealed that the DEGs were mainly involved in the synthesis of amide compounds, zinc finger proteins, transmembrane transporters, etc. In summary, our results indicate that the development of Bsr-d1 knockout mutants through CRISPR/Cas9 can enhance the broad-spectrum resistance of rice in Northeast China to rice blast. This study not only provides a theoretical basis for disease resistance breeding involving the Bsr-d1 gene in Northeast China, but also provides new germplasm resources for disease-resistance rice breeding.


Asunto(s)
Magnaporthe , Oryza , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sistemas CRISPR-Cas , Fitomejoramiento , Alelos , Factores de Transcripción/genética , Oryza/genética , Oryza/metabolismo , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética
5.
Opt Lett ; 48(15): 3845-3848, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37527064

RESUMEN

A novel high-sensitivity temperature sensor based on a chirped thin-core fiber Bragg grating Fabry-Perot interferometer (CTFBG-FPI) and the Vernier effect is proposed and demonstrated. With femtosecond laser direct writing technology, two CTFBG-FPIs with different interferometric cavity lengths are inscribed inside a thin-core fiber to form a Vernier effect system. The two FPIs consist of two pairs of CTFBGs with a full width at half maximum (FWHM) of 66.5 nm staggered in parallel. The interferometric cavity lengths of the two FPIs were designed to be 2 mm and 1.98 mm as the reference arm and sensing arm of the sensor, respectively. The temperature sensitivity of this sensor was measured to be -1.084 nm/°C in a range of 40-90°C. This sensor is expected to play a crucial role in precision temperature measurement applications.

6.
Int Wound J ; 20(9): 3457-3466, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37269235

RESUMEN

Deep sternal wound infection (DSWI) is a relatively complex wound in wound reconstruction surgery. Because plastic surgeons deal with DSWI patients late. The primary healing (healing by first intention) after reconstruction of DSWI is restricted by many preoperative risk factors. The purpose of this study is to explore and analyse the risk factors of primary healing failure in patients with DSWI treated with platelet-rich plasma (PRP) and negative pressure trauma therapy (NPWT). 115 DSWI patients treated with the PRP and NPWT (PRP + NPWT) modality were retrospectively (2013-2021) analysed. They were divided into two groups according to primary healing results after the first PRP + NPWT treatment. Univariate and multivariate analyses were used to compare the data of the two groups to find out the risk factors and their optimal cut-off values were identified by ROC analysis. The primary healing results, debridement history, wound size, sinus, osteomyelitis, renal function, bacterial culture, albumin (ALB), platelet (PLT) between the two groups were significantly different (P < 0.05). Binary logistic regression showed that osteomyelitis, sinus, ALB and PLT were the risk factors affecting primary healing outcomes (P < 0.05). ROC analysis showed that AUC for ALB in the non-primary healing group was 0.743 (95% CI: 0.650-0.836, P < 0.05) and its optimal cutoff value of 31 g/L was associated with primary healing failure with a sensitivity of 96.9% and specificity of 45.1%. AUC for PLT in the non-primary healing group was 0.670 (95% CI: 0.571 ~ 0.770, P < 0.05) its optimal cutoff value of 293 × 109 /L was associated with primary healing failure with a sensitivity of 72.5% and specificity of 56.3%. In the cases included in this study, the success rate of primary healing of DSWI treated with PRP + NPWT was not affected by the most common preoperative risk factors for wound non-union. It is indirectly confirmed that PRP + NPWT is an ideal treatment. However, it should be noted that it will still be adversely affected by sinus osteomyelitis, ALB and PLT. The patients need to be carefully evaluated and corrected before reconstruction.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Terapia de Presión Negativa para Heridas , Osteomielitis , Plasma Rico en Plaquetas , Humanos , Esternotomía/efectos adversos , Infección de la Herida Quirúrgica/terapia , Infección de la Herida Quirúrgica/etiología , Estudios Retrospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Factores de Riesgo , Osteomielitis/cirugía , Osteomielitis/complicaciones , Terapia de Presión Negativa para Heridas/métodos
7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(9): 1377-1387, 2023.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38044649

RESUMEN

Non-coding RNA (ncRNA) refers to RNA that lack the ability to encode protein. Based on their distinct biological characteristics, ncRNA are mainly classified into microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNA plays a crucial regulatory role in various biological processes. Pregnancy is a highly intricate physiological process that requires successful completion of multiple steps. Embryo implantation, as a key event of pregnancy, which is regulated by numerous factors, including embryo development, endometrial changes, and the maternal-embryo crosstalk. A diverse array of regulatory mechanisms ensures the accomplishment of embryo localization, adhesion, invasion, and ultimately successful implantation. MiRNA, lncRNA, and circRNA are extensively studied ncRNA molecules at present, which play an important role in the physiological and pathological processes associated with embryo implantation through targeting and regulating the expression of multiple cytokine and genes. With advancements in molecular biology technology, it is anticipated that ncRNA will contribute to the prediction and enhancement of clinical pregnancy outcomes from a molecular perspective.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Embarazo , Femenino , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Circular , Implantación del Embrión/genética , ARN no Traducido/genética , MicroARNs/genética , MicroARNs/metabolismo
8.
Molecules ; 27(24)2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36557828

RESUMEN

Pectolinarin and linarin are two major flavone O-glycosides of Cirsium japonicum, which has been used for thousands of years in traditional Chinese medicine. Pharmacological research on pectolinarin and linarin is meaningful and necessary. Here, a process for the purification of pectolinarin and linarin from C. japonicum was established using macroporous resin enrichment followed by prep-HPLC separation. The results show the purity of pectolinarin and linarin reached 97.39% and 96.65%, respectively. The in vitro bioactivities result shows the ORAC values of pectolinarin and linarin are 4543 and 1441 µmol TE/g, respectively, meanwhile their inhibition rate of BSA-MGO-derived AGEs is 63.58% and 19.31% at 2 mg/mL, which is 56.03% and 30.73% in the BSA-fructose system, respectively. The COX-2 inhibition rate at 50 µg/mL of linarin and pectolinarin reached 55.35% and 40.40%, respectively. Furthermore, the in vivo bioassay combining of histopathologic evaluation and biochemical analysis of liver glutamic oxaloacetic transaminase, serum creatinine and TNF-α show pectolinarin can alleviate lipopolysaccharide (LPS)-induced acute liver and kidney injury in mice. Metabolomics analysis shows that pectolinarin attenuates LPS-challenged liver and kidney stress through regulating the arachidonic acid metabolism and glutathione synthesis pathways. Collectively, our work presents a solid process for pectolinarin and linarin purification and has discovered a promising natural therapeutic agent-pectolinarin.


Asunto(s)
Cirsium , Ratones , Animales , Lipopolisacáridos , Glicósidos/farmacología
9.
Nanotechnology ; 30(34): 345604, 2019 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-31067524

RESUMEN

A highly sensitive and uniform three-dimensional (3D) surface-enhanced Raman spectroscopy (SERS) substrate has been fabricated by in situ ultraviolet ozone cleaning and layer-by-layer self-assembly. The SERS properties and the structural changes of the substrates were systematically studied by adjusting the cleaning time upon the in situ and post cleaning strategy. Under the optimal cleaning condition, the cleaning technology could give rise to clean and optimal surfaces for SERS analysis, thus obtaining efficient plasmonic films populated with a large number of homogeneous 'hot-spots'. Then with the optimal monolayer film, the SERS performance derived from plasmon coupling in multilayers of the Au@Ag nanocubes substrates was explored. It demonstrated that the plasmon coupling between layers (out-of-plane) contributed much to the SERS intensity, leading a more superior SERS enhancement from the 3D SERS substrates than that from the conventional two-dimensional SERS substrates. Also the in situ cleaning 3D SERS substrates displayed a nice uniformity and excellent time stability. With this method, the optimized substrates were further used to detect prohibited pigments in drink with an excellent linear relationship between characteristic peak intensity and analytes concentration over wide concentration ranges. Our experimental results clearly show that the in situ cleaning 3D SERS substrates provide an ideal candidate for SERS applications in food safety.

10.
Molecules ; 24(13)2019 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-31277495

RESUMEN

Carbon Bond Mechanism IV (CBM-IV) is a widely used reaction mechanism in which VOCs are grouped according to the molecular structure. In the present study, we applied a sensitivity analysis on the CBM-IV mechanism to clarify the importance of each reaction under two different initial conditions (urban and low-NO scenarios). The reactions that exert minor influence on the reaction system are then screened out from the mechanism, so that a reduced version of the CBM-IV mechanism under specific initial conditions can be obtained. We found that in a typical urban condition, 11 reactions can be removed from the original CBM-IV mechanism, and the deviation is less than 5% between the results using the original CBM-IV mechanism and the reduced mechanism. Moreover, in a low-NO initial condition, two more reactions, both of which are nitrogen-associated reactions, can be screened out from the reaction mechanism, while the accuracy of the simulation is still maintained. It is estimated that the reduction of the CBM-IV mechanism can save 11-14% of the computing time in the calculation of the chemistry in a box model simulation.


Asunto(s)
Carbono/química , Simulación por Computador , Modelos Teóricos , Ozono/análisis
11.
Langmuir ; 34(21): 6077-6084, 2018 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-29747504

RESUMEN

Because of their perfect geometrical symmetry, spherical metal nanoparticles have attracted much attention for various applications, including fundamental studies and construction of plasmonic devices. In this work, monodisperse silver nanospheres (Ag NSs) in aqueous solution were directly prepared by a continuous process of seed-mediated growth followed by oxidative etching. Silver nanocubes (Ag NCs) were synthesized by a seed-mediated growth method and subsequently were transformed to Ag NSs by simple injection of Cu2+ to the freshly prepared Ag NCs solution. Not requiring any centrifugation steps at both growth and etching stages makes this procedure convenient and efficient. The etching process and morphology evolution of silver nanostructure were monitored by UV-vis spectromater, SEM, and XRD. Monodisperse Ag NSs with broadly tunable diameters (from 37 to 68 nm) have been successfully prepared. The optical property of Ag NSs has been studied and the experimental results show fairly good consistency with simulation results. Furthermore, these Ag NSs prepared by our approach could be constructed into ordered superlattice by self-assembly technique based on their high monodispersity and sphericity.

12.
J Sep Sci ; 39(7): 1310-5, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26791136

RESUMEN

A new type of molecularly imprinted ionic liquid magnetic microspheres was synthesized by aqueous suspension polymerization, using 4,4'-dichlorobenzhydrol as a dummy template, and 1-allyl-3-ethylimidazolium hexafluorophosphate and methacrylic acid as co-functional monomers. The results of morphology and magnetic property evaluation of the obtained microspheres demonstrated that it was monodispersed spherical, possessed a rough surface, and an outstanding magnetic properties. Binding experiments revealed that it had a substantial adsorption capacity and strong recognition ability to organochlorine pesticides (OCPs) in aqueous solution. Then the microspheres were applied as an adsorbent of magnetic dispersive solid-phase extraction for the selective recognition and rapid determination of OCPs in environmental water. Under the optimum conditions, good linearity of the three types of OCPs (dicofol, tetradifon, and p,p'-dichlorodiphenyldichloroethane) was achieved in the range of 1.0-100 ng/mL (r ≥ 0.9994). The recoveries at three spiking levels ranged from 82.6 to 100.4% with the RSDs less than 6.9%.

13.
Anal Bioanal Chem ; 406(11): 2669-77, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24573579

RESUMEN

Ionic liquid-modified magnetic polymeric microspheres (ILMPM) were prepared based on Fe3O4 magnetic nanoparticles (MNPs) and ionic liquids (ILs) incorporated into a polymer. The composites were characterized using scanning electron microscopy, Fourier transform infrared analysis, thermogravimetric analysis, X-ray diffraction, and vibrating magnetometer, which indicated that ILMPM had a regularly spherical shape and strong magnetic property. The obtained ILMPM were successfully applied as a special adsorbent of magnetic dispersive solid phase extraction (MDSPE) for the rapid extraction and isolation of sulfamonomethoxine sodium and sulfachloropyrazine sodium in urine. The factors that affected extraction efficiency, such as adsorption conditions, desorption conditions, washing and elution solvents, and pH of the sample solution, were optimized. Under the optimum condition, good linearity in the range of 0.005-2.0 µg g(-1) (r ≥ 0.9996) was obtained for the two sulfonamides (SAs); the average recoveries at three spiked levels ranged from 86.9 to 102.1 %, with relative standard deviations of ≤4.3 %. The presented ILMPM-MDSPE method combined the advantages of ILs, MNPs, and MDSPE and therefore could be potentially applied for rapid screening of SAs in urine.


Asunto(s)
Polímeros/química , Extracción en Fase Sólida/instrumentación , Sulfamonometoxina/aislamiento & purificación , Sulfanilamidas/aislamiento & purificación , Adsorción , Humanos , Líquidos Iónicos/química , Fenómenos Magnéticos , Microesferas , Extracción en Fase Sólida/métodos , Sulfamonometoxina/orina , Sulfanilamidas/orina
14.
Food Chem ; 445: 138738, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38364497

RESUMEN

This study successfully encapsulated the Ag+-doped Au nanoclusters (Ag/AuNCs) within the ZIF-8 framework to construct a novel Ag/AuNCs@ZIF-8 ratiometric fluorescent probe for the antibiotic doxycycline (DOX) detection. The incorporation of Ag+ contributed to the fluorescence enhancement of the nanoclusters through the "silver effect", consequently improving the stability of the developed bimetallic Ag/AuNCs. Furthermore, the encapsulation of bimetallic Ag/AuNCs within the ZIF-8 framework restricted their intramolecular vibrations, resulting in further amplification of fluorescence intensity at 595 nm. The ZIF-8 also sensitized the restoration of DOX green fluorescence at 515 nm. Within the concentration range of 0.001-20 µg mL-1, the ratio of fluorescence intensity (F515/F595) exhibited a favorable linearity for DOX concentration, with a detection limit of 36.8 ng mL-1. This ratiometric fluorescence approach had the promising potential for accurate and efficient quantitative detection of DOX residue in food and served as a valuable reference for rapid monitoring of food contaminants.


Asunto(s)
Nanopartículas del Metal , Nanopartículas del Metal/química , Doxiciclina , Oro/química , Espectrometría de Fluorescencia , Colorantes Fluorescentes/química
15.
Int J Surg ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38573065

RESUMEN

OBJECTIVES: Accurate preoperative prediction of the pathological grade of clear cell renal cell carcinoma (ccRCC) is crucial for optimal treatment planning and patient outcomes. This study aims to develop and validate a deep-learning (DL) algorithm to automatically segment renal tumours, kidneys, and perirenal adipose tissue (PRAT) from computed tomography (CT) images and extract radiomics features to predict the pathological grade of ccRCC. METHODS: In this cross-ethnic retrospective study, a total of 614 patients were divided into a training set (383 patients from the local hospital), an internal validation set (88 patients from the local hospital), and an external validation set (143 patients from the public dataset). A two-dimensional TransUNet-based DL model combined with the train-while-annotation method was trained for automatic volumetric segmentation of renal tumours, kidneys, and visceral adipose tissue (VAT) on images from two groups of datasets. PRAT was extracted using a dilation algorithm by calculating voxels of VAT surrounding the kidneys. Radiomics features were subsequently extracted from three regions of interest of CT images, adopting multiple filtering strategies. The least absolute shrinkage and selection operator (LASSO) regression was used for feature selection, and the support vector machine (SVM) for developing the pathological grading model. Ensemble learning was used for imbalanced data classification. Performance evaluation included the Dice coefficient for segmentation and metrics such as accuracy and area under curve (AUC) for classification. The WHO/International Society of Urological Pathology (ISUP) grading models were finally interpreted and visualized using the SHapley Additive exPlanations (SHAP) method. RESULTS: For automatic segmentation, the mean Dice coefficient achieved 0.836 for renal tumours and 0.967 for VAT on the internal validation dataset. For WHO/ISUP grading, a model built with features of PRAT achieved a moderate AUC of 0.711 (95% CI, 0.604-0.802) in the internal validation set, coupled with a sensitivity of 0.400 and a specificity of 0.781. While model built with combination features of the renal tumour, kidney, and PRAT showed an AUC of 0.814 (95% CI, 0.717-0.889) in the internal validation set, with a sensitivity of 0.800 and a specificity of 0.753, significantly higher than the model built with features solely from tumour lesion (0.760; 95% CI, 0.657-0.845), with a sensitivity of 0.533 and a specificity of 0.767. CONCLUSION: Automated segmentation of kidneys and visceral adipose tissue (VAT) through TransUNet combined with a conventional image morphology processing algorithm offers a standardized approach to extract PRAT with high reproducibility. The radiomics features of PRAT and tumour lesions, along with machine learning, accurately predict the pathological grade of ccRCC and reveal the incremental significance of PRAT in this prediction.

16.
Comput Biol Med ; 173: 108339, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38547658

RESUMEN

The application of Artificial Intelligence (AI) to screen drug molecules with potential therapeutic effects has revolutionized the drug discovery process, with significantly lower economic cost and time consumption than the traditional drug discovery pipeline. With the great power of AI, it is possible to rapidly search the vast chemical space for potential drug-target interactions (DTIs) between candidate drug molecules and disease protein targets. However, only a small proportion of molecules have labelled DTIs, consequently limiting the performance of AI-based drug screening. To solve this problem, a machine learning-based approach with great ability to generalize DTI prediction across molecules is desirable. Many existing machine learning approaches for DTI identification failed to exploit the full information with respect to the topological structures of candidate molecules. To develop a better approach for DTI prediction, we propose GraphormerDTI, which employs the powerful Graph Transformer neural network to model molecular structures. GraphormerDTI embeds molecular graphs into vector-format representations through iterative Transformer-based message passing, which encodes molecules' structural characteristics by node centrality encoding, node spatial encoding and edge encoding. With a strong structural inductive bias, the proposed GraphormerDTI approach can effectively infer informative representations for out-of-sample molecules and as such, it is capable of predicting DTIs across molecules with an exceptional performance. GraphormerDTI integrates the Graph Transformer neural network with a 1-dimensional Convolutional Neural Network (1D-CNN) to extract the drugs' and target proteins' representations and leverages an attention mechanism to model the interactions between them. To examine GraphormerDTI's performance for DTI prediction, we conduct experiments on three benchmark datasets, where GraphormerDTI achieves a superior performance than five state-of-the-art baselines for out-of-molecule DTI prediction, including GNN-CPI, GNN-PT, DeepEmbedding-DTI, MolTrans and HyperAttentionDTI, and is on a par with the best baseline for transductive DTI prediction. The source codes and datasets are publicly accessible at https://github.com/mengmeng34/GraphormerDTI.


Asunto(s)
Inteligencia Artificial , Descubrimiento de Drogas , Evaluación Preclínica de Medicamentos , Redes Neurales de la Computación , Benchmarking
17.
Nat Commun ; 15(1): 44, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168070

RESUMEN

Tubulin-based microtubule is a core component of flagella axoneme and essential for sperm motility and male fertility. Structural components of the axoneme have been well explored. However, how tubulin folding is regulated in sperm flagella formation is still largely unknown. Here, we report a germ cell-specific co-factor of CCT complex, STYXL1. Deletion of Styxl1 results in male infertility and microtubule defects of sperm flagella. Proteomic analysis of Styxl1-/- sperm reveals abnormal downregulation of flagella-related proteins including tubulins. The N-terminal rhodanese-like domain of STYXL1 is important for its interactions with CCT complex subunits, CCT1, CCT6 and CCT7. Styxl1 deletion leads to defects in CCT complex assembly and tubulin polymerization. Collectively, our findings reveal the vital roles of germ cell-specific STYXL1 in CCT-facilitated tubulin folding and sperm flagella development.


Asunto(s)
Proteómica , Tubulina (Proteína) , Masculino , Humanos , Tubulina (Proteína)/metabolismo , Motilidad Espermática/genética , Semen/metabolismo , Espermatozoides/metabolismo , Flagelos/metabolismo , Axonema/metabolismo
18.
Animals (Basel) ; 13(20)2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37893907

RESUMEN

Weaning is an important period that affects the performance of piglets. However, the regulation of dietary amino acid levels is considered to be an effective way to alleviate the weaning stress of piglets. N-carbamylglutamate (NCG) plays an important role in improving the growth performance and antioxidant capacity of animals. A total of 36 weaned piglets were randomly assigned to two treatment groups, a control group (CON) and a 500 mg/kg NCG group (NCG), and the experiment lasted for 28 days. The results show that the NCG treatment group showed an increased 0-28 days average weight gain and average daily feed intake, and also increased contents of GLU and HDL, and lower SUN in serum, and an upregulation of the expression of the amino acid transporters SNAT2, EAAC1, SLC3A1, and SLC3A2 mRNA in the jejunum (p < 0.05), as well as an increased villus length and VH:CD ratio, and claudin-1, occludin, and ZO-1 mRNA expression in the jejunum (p < 0.05). The NCG treatment group showed an increased content of GSH-Px in serum and T-AOC and SOD in the jejunum, and a lower content of MDA (p < 0.05); and the upregulation of the mRNA expression related to antioxidant enzymes (CAT, SOD1, Gpx4, GCLC, GCLM and Nrf2, AhR, CYP1A1) in the jejunal mucosa (p < 0.05). In addition, compared with the control group, the NCG treatment group saw an upregulation in the mRNA expression of IL-10 and a decrease in the expression of IL-1ß and IL-4 in the jejunal mucosa (p < 0.05). In summary, the results of this study suggest that NCG improved growth performance and jejunal morphology, improved the jejunal transport of amino acids related to the ornithine cycle, and improved the antioxidant capacity in weaned pigs.

19.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 4): m503, 2012 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-22589856

RESUMEN

Copper nitrate in methanol solution cleaves the N-C(methanol) bond when reacted with 3-methyl-5-phenyl-pyrazole-1-methanol to yield the centrosymmetric dinuclear title compound, [Cu(2)(CH(3)O)(2)(NO(3))(2)(C(10)H(10)N(2))(4)], in which the Cu(II) atom is linked to a nitrate ion, two methano-late ions and two pyrazole ligands in a distorted square-pyramidal environment. The O atom of the nitrate anion occupies the apical site. The crystal structure features intra-molecular N-H⋯O hydrogen bonds.

20.
Anal Methods ; 14(42): 4245-4251, 2022 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-36250613

RESUMEN

Two kinds of copper-based metal fluorescent nanoclusters were successfully prepared by the chemical reduction method; one of them (CuNCs) was synthesized by direct reduction of copper sulfate, and the other (CuAuNCs) was synthesized by the stepwise addition of copper salt and chloroauric acid. CuNCs were used to establish the fluorescence resonance energy transfer (FRET) system with neutral red (NR) due to the supramolecular effect of ß-cyclodextrin (ß-CD) modified on the surface of CuNCs. NR could enter the hydrophobic cavity of ß-CD and narrow the distance between CuNCs and NR, which could lead to FRET. Fluorescence was transferred from CuNCs to NR, resulting in amplification of the NR fluorescence signal, which could be used to detect vanillin. In addition, CuAuNCs with strong fluorescence were used as fluorescent probes to detect vanillin through the quenching mechanism. By comparison, the simplicity of CuNC synthesis and the high selectivity of ß-CD made the FRET method more practical, which may provide a new strategy for assaying vanillin.


Asunto(s)
Cobre , Transferencia Resonante de Energía de Fluorescencia , Cobre/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Espectrometría de Fluorescencia/métodos , Benzaldehídos
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