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1.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576206

RESUMO

Actinobacillus pleuropneumoniae is a pathogen that infects pigs and poses a serious threat to the pig industry. The emergence of quinolone-resistant strains of A.pleuropneumoniae further limits the choice of treatment. However, the mechanisms behind quinolone resistance in A.pleuropneumoniae remain unclear. The genomes of a ciprofloxacin-resistant strain, A. pleuropneumoniae SC1810 and its isogenic drug-sensitive counterpart were sequenced and analyzed using various bioinformatics tools, revealing 559 differentially expressed genes. The biological membrane, plasmid-mediated quinolone resistance genes and quinolone resistance-determining region were detected. Upregulated expression of efflux pump genes led to ciprofloxacin resistance. The expression of two porins, OmpP2B and LamB, was significantly downregulated in the mutant. Three nonsynonymous mutations in the mutant strain disrupted the water-metal ion bridge, subsequently reducing the affinity of the quinolone-enzyme complex for metal ions and leading to cross-resistance to multiple quinolones. The mechanism of quinolone resistance in A. pleuropneumoniae may involve inhibition of expression of the outer membrane protein genes ompP2B and lamB to decrease drug influx, overexpression of AcrB in the efflux pump to enhance its drug-pumping ability, and mutation in the quinolone resistance-determining region to weaken the binding of the remaining drugs. These findings will provide new potential targets for treatment.

2.
Sci Rep ; 11(1): 18407, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526634

RESUMO

The main objective of this study is to analyze the clinical and pathological features and prognosis of patients with Hepatitis B associated membranous nephropathy (HBV-MN) and idiopathic membranous nephropathy (IMN) complicated with hepatitis B virus (HBV) infection. This study will provide more basis for diagnosis and prognosis evaluation. A total of 50 patients with HBV-MN were included in this study. 56 IMN patients complicated with HBV infection diagnosed during the same period formed the control group. Parameters including blood routine, urine routine and plasma levels of albumin (ALB), serum creatinine (SCR), blood urea nitrogen (BUN), urea acid (UA), total cholesterol (T-CHO), triglycerides (TG), complement C3 and C4, glutamic pyruvic transaminase (ALT), glutamic pyruvic transaminase (AST), 24-h urinary protein quantification (24 h-TP), renal phospholipase A2 receptor (PLA2R) and HBV related markers during the hospitalization and outpatient follow-up study period were collected for all the patients. The proportion of male patients was high in both groups. The average age of the HBV-MN group was 37.2 ± 14.187 years old, it was younger compared with the IMN group (P = 0.003). Nephrotic syndrome was the major clinical manifestation among patients. There was no significant difference between the two groups in the levels of anemia, microscopic hematuria, renal dysfunction, liver dysfunction, liver cirrhosis. The level of serum C3 and C4 in the HBV-MN group was lower compared with the IMN group (P = 0.002, P = 0.014). In the HBV-MN group, serum HBV markers were negative in 6 (12%) patients, 4 patients (8%) were positive for PLA2R in serum, and 5 patients (10%) were positive for PLA2R in renal tissue. Stronger IgG1 and C1q and weaker IgG4 staining were found in HBV-MN group renal tissues (P = 0.003, P = 0.025, and P = 0.001, respectively). There were no statistical differences compared with serum and renal PLA2R between HBV-MN and IMN groups (P = 0.098, P = 0.109). During the 1-year follow-up, there was no significant difference in complete remission rate between the two groups (P = 0.7739). Renal biopsy is crucial to diagnose HBV-MN. IgG subtypes in the HBV-MN group were mainly IgG1 deposition, while those in IMN complicated with HBV infection group were mainly IgG4 deposition. When HBV-associated antigen and PLA2R are present in renal tissue, lower level of serum C3 and C4, high intensity of renal C1q and IgG1 is more supportive of HBV-MN. The positive of PLA2R in serum and renal tissue in differentiating HBV from IMN complicated with HBV infection remains to be discussed.

3.
Exp Cell Res ; 407(2): 112806, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34487727

RESUMO

At present, there are still many poorly understood aspects of the mechanisms underlying hepatocellular carcinoma (HCC) invasion and metastasis. Invadopodia are important structures for cancer cell invasion and metastasis. We determined that high T-lymphoma invasion and metastasis 1 (Tiam1) expression is associated with HCC invasion and metastasis and poor patient prognosis after surgery. Gain- and loss-of-function studies confirmed that Tiam1 promotes invadopodia formation in HCC by activating Rac1. A series of biochemical experiments confirmed that this effect is regulated by the PI3K/Akt signaling pathway. We also confirmed that PIP2 facilitates this effect. In summary, these findings reveal that Tiam1 plays an important role in invadopodia formation in HCC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34366329

RESUMO

BACKGROUND: Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. OBJECTIVE: To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. METHODS: Consecutive LT patients who underwent CEUS examinations at 1-4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. RESULTS: Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2-4 (all P <  0.05) and a higher slope of CEUS score progression (0.480 vs -0.044, P <  0.001). The accuracy of CEUS in identifying NAS improved over time after LT, reaching its maximum at week 4, with a sensitivity of 66.7%, a specificity of 87.9%, a positive predictive value (PPV) of 75.9%, a negative predictive value (NPV) of 82.3%, and an accuracy of 80.2%in the full cohort when a CEUS score≥3 was used as the cut-off. Multivariate analysis identified gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT) and the CEUS score at week 4 as independent predictors of NAS. In the task of identifying NAS, an NAS score combining the above 3 variables at week 4 showed areas under the receiver operating characteristic curve of 0.88 (95%CI, 0.78-0.99) in the estimation group (n = 60) and 0.82 (95%CI, 0.69-0.96) in the validation group (n = 56). An NAS score cut-off of 0.396 identified 87.2%of NAS cases in the estimation group, with a PPV of 93.3%; and 75.0%of NAS cases in the validation group, with a PPV of 58.8%. CONCLUSIONS: CEUS examination during the first 4 weeks is useful in assessing the risk of NAS within 1 year after LT. In particular, an NAS score combining the CEUS score, GGT level, and ALT level at week 4 can be used to accurately predict the risk of NAS in LT patients.

5.
Nat Commun ; 12(1): 4849, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381032

RESUMO

Although various artificial protein nanoarchitectures have been constructed, controlling the transformation between different protein assemblies has largely been unexplored. Here, we describe an approach to realize the self-assembly transformation of dimeric building blocks by adjusting their geometric arrangement. Thermotoga maritima ferritin (TmFtn) naturally occurs as a dimer; twelve of these dimers interact with each other in a head-to-side manner to generate 24-meric hollow protein nanocage in the presence of Ca2+ or PEG. By tuning two contiguous dimeric proteins to interact in a fully or partially side-by-side fashion through protein interface redesign, we can render the self-assembly transformation of such dimeric building blocks from the protein nanocage to filament, nanorod and nanoribbon in response to multiple external stimuli. We show similar dimeric protein building blocks can generate three kinds of protein materials in a manner that highly resembles natural pentamer building blocks from viral capsids that form different protein assemblies.


Assuntos
Nanoestruturas/química , Proteínas/química , Cálcio/química , Ferritinas/química , Nanoestruturas/ultraestrutura , Nanotecnologia , Polietilenoglicóis/química , Multimerização Proteica , Thermotoga maritima
6.
Vaccines (Basel) ; 9(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34451943

RESUMO

Pegivirus, HPgV, which was earlier known as Gb virus and hepatitis G virus, is an enveloped, positive-stranded RNA and lymphotropic virus classified into the Flaviviridae family. The transmission routes primarily involve blood products, and infections are worldwide, leading up to 25% of persistent infections. To date, no effective therapeutic means are available to clear Pegivirus infections. Effective vaccine therapeutics is the best alternative to manage this disease and any associated potential pandemic. Thus, whole proteome-based mining of immunogenic peptides, i.e., CTL (cytotoxic T lymphocytes), HTL (helper T lymphocytes), and B cell epitopes, was mapped to design a vaccine ensemble. Our investigation revealed that 29 different epitopes impart a critical role in immune response induction, which was also validated by exploring its physiochemical properties and experimental feasibility. In silico expression and host immune simulation were examined using an agent-based modeling approach and confirmed the induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.

7.
Cancer Med ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418326

RESUMO

FNDC4 is highly homologous to the exercise-associated myokine FNDC5/irisin, which is highly expressed and promotes the invasion and metastasis of HCC cells. However, the function of FNDC4 remains unknown. Here, we report that FNDC4, an extracellular factor, plays important roles in the invasion and metastasis of HCC. We found that high FNDC4 expression is associated with poor survival in HCC patients and FNDC4 promotes the migration and invasion of HCC cells. Mechanistically, we found that FNDC4 is related to the PI3K/Akt signalling pathway to a certain extent. Specifically, the extracellular domain of FNDC4 acts as an extracellular factor to promote Akt phosphorylation levels in this pathway. These findings reveal that FNDC4 promotes the invasion and metastasis of HCC partly via the PI3K/Akt signalling pathway.

8.
Int J Hyperthermia ; 38(1): 1060-1068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265235

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) has been recommended as the treatment for benign thyroid nodules (BTNs) by some guidelines. However, detailed follow-up instructions for thyroid function about the timing and affected populations after RFA are lacked due to insufficient researches. This 12-month prospective study aimed to evaluate the incidence and risk factors of thyroid dysfunction at different time points after RFA, especially within 1 week that previous studies didn't concern. METHODS: Seventy-five euthyroid patients who underwent RFA for symptomatic BTNs were enrolled (ChiCTR-INR-16007884). The incidence of thyroid dysfunction within 1 week, at 1, 6, and 12 months after RFA was evaluated. The risk factors for different types of thyroid dysfunction in the different terms were further analyzed. RESULTS: Within 1 week after RFA, the incidence of thyroid dysfunction was as high as 36.00% unexpectedly, and only overt thyrotoxicosis and subclinical thyrotoxicosis occurred, which were significantly associated with the low-normal baseline thyrotropin (TSH) level (p = 0.001) and high ablation volume ratio (p = 0.008). From 1 to 12 months (the long term), the incidence dropped significantly and remained low (8.00-12.00%); and thyroid dysfunction presented as overt thyrotoxicosis, subclinical thyrotoxicosis, and subclinical hypothyroidism. The long-term thyrotoxicosis group had more cases with diabetes and lower baseline TSH levels. The long-term subclinical hypothyroidism group had more cases with positive thyroid peroxidase antibodies, higher baseline TSH levels, and higher ablation volume ratios. CONCLUSIONS: After the RFA of BTNs, thyroid dysfunction was more likely to occur within 1 week and in populations with risk factors.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Ablação por Cateter/efeitos adversos , Humanos , Estudos Prospectivos , Ablação por Radiofrequência/efeitos adversos , Fatores de Risco , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento
9.
J Clin Ultrasound ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240426

RESUMO

Acute transient swelling (ATS) of the thyroid is a rare complication following fine-needle aspiration (FNA) of thyroid nodules. We present 31 cases with 35 nodules encountered at our institute and reported in the literature, to provide further information. The incidence rate in our institute was 0.46%. Of these nodules, 74.3% (26/35) were solid, 65.7% (23/35) exhibited hypervascularity, and 77.2% (27/35) were benign or follicular neoplasms. Although most cases (87.1%, 27/31) occurred within 2 h after FNA, four patients experienced delayed ATS after 7 h to 2 days. Therefore, awareness of this complication, especially its delayed occurrence, should be raised.

10.
Sensors (Basel) ; 21(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34300400

RESUMO

This study primarily investigates image sensing at low sampling rates with convolutional neural networks (CNN) for specific applications. To improve the image acquisition efficiency in energy-limited systems, this study, inspired by compressed sensing, proposes a fully learnable model for task-driven image-compressed sensing (FLCS). The FLCS, based on Deep Convolution Generative Adversarial Networks (DCGAN) and Variational Auto-encoder (VAE), divides the image-compressed sensing model into three learnable parts, i.e., the Sampler, the Solver and the Rebuilder. To be specific, a measurement matrix suitable for a type of image is obtained by training the Sampler. The Solver calculates the image's low-dimensional representation with the measurements. The Rebuilder learns a mapping from the low-dimensional latent space to the image space. All the mentioned could be trained jointly or individually for a range of application scenarios. The pre-trained FLCS reconstructs images with few iterations for task-driven compressed sensing. As indicated from the experimental results, compared with existing approaches, the proposed method could significantly improve the reconstructed images' quality while decreasing the running time. This study is of great significance for the application of image-compressed sensing at low sampling rates.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Redes Neurais de Computação
11.
World J Surg Oncol ; 19(1): 171, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118947

RESUMO

The purpose of this letter to the Editor is to report some shortcomings in the statistical analysis and variable grouping in the recent publication of the article "Clinical outcomes of chondroblastoma treated using synthetic bone substitute: risk factors for developing radiographic joint degeneration," and to further explore some of the factors that may affect the clinical prognosis of chondroblastoma patients. We also suggest future prospective controlled studies with large samples to improve the limitations encountered by Outani et al. (World J Surg Oncol. 18(1):47, 2020) due to insufficient statistical power of variables and lack of controls.


Assuntos
Neoplasias Ósseas , Substitutos Ósseos , Condroblastoma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , Humanos , Prognóstico , Fatores de Risco
12.
Global Spine J ; : 21925682211005732, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33896211

RESUMO

STUDY DESIGN: Retrospective pooled analysis of individual patient data. OBJECTIVES: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. METHODS: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. RESULTS: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. CONCLUSION: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

13.
Biomed Res Int ; 2021: 8811056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791381

RESUMO

Objectives: To build and validate random forest (RF) models for the classification of bone tumors based on the conventional radiographic features of the lesion and patients' clinical characteristics, and identify the most essential features for the classification of bone tumors. Materials and Methods: In this retrospective study, 796 patients (benign bone tumors: 412 cases, malignant bone tumors: 215 cases, intermediate bone tumors: 169 cases) with pathologically confirmed bone tumors from Nanfang Hospital of Southern Medical University, Foshan Hospital of TCM, and University of Hong Kong-Shenzhen Hospital were enrolled. RF models were built to classify tumors as benign, malignant, or intermediate based on conventional radiographic features and potentially relevant clinical characteristics extracted by three musculoskeletal radiologists with ten years of experience. SHapley Additive exPlanations (SHAP) was used to identify the most essential features for the classification of bone tumors. The diagnostic performance of the RF models was quantified using receiver operating characteristic (ROC) curves. Results: The features extracted by the three radiologists had a satisfactory agreement and the minimum intraclass correlation coefficient (ICC) was 0.761 (CI: 0.686-0.824, P < .001). The binary and tertiary models were built to classify tumors as benign, malignant, or intermediate based on the imaging and clinical features from 627 and 796 patients. The AUC of the binary (19 variables) and tertiary (22 variables) models were 0.97 and 0.94, respectively. The accuracy of binary and tertiary models were 94.71% and 82.77%, respectively. In descending order, the most important features influencing classification in the binary model were margin, cortex involvement, and the pattern of bone destruction, and the most important features in the tertiary model were margin, high-density components, and cortex involvement. Conclusions: This study developed interpretable models to classify bone tumors with great performance. These should allow radiographers to identify imaging features that are important for the classification of bone tumors in the clinical setting.


Assuntos
Neoplasias Ósseas/classificação , Neoplasias Ósseas/diagnóstico por imagem , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Phytomedicine ; 85: 153551, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33827043

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC), lacking targeted therapies currently, is susceptible to ferroptosis, a recently defined form of cell death. PURPOSE: To evaluate the anticancer activity of Shuganning injection (SGNI), a traditional Chinese patent medicine, on TNBC cells; To elucidate the mechanism of SGNI induced ferroptosis. METHODS: The anticancer activity of SGNI was examined via in vitro cell proliferation assays and in vivo xenograft growth assay. Ferroptosis was determined by flow-cytometric analysis of lipid ROS, labile iron pool measurement, and propidium iodide exclusion assay. The dependency on heme oxygenase 1 (HO-1) of SGNI induced ferroptosis was confirmed by genetic knockdown and pharmacological inhibition of the protein. RESULTS: SGNI selectively inhibited the proliferation of TNBC cells compared to non-TNBC breast cancer cells and normal cells. The cell death induced by SGNI in TNBC cells showed distinct morphology from apoptosis and could not be rescued by the pan-caspase inhibitor Z-VAD(OMe)-FMK. On the other hand, SGNI induced cell death was blocked by the lipid ROS scavengers ferrostatin-1 and liproxstatin-1, the acyl-CoA synthetase long chain family member 4 inhibitor rosiglitazone, and the iron chelators 1,10-phenanthroline and deferoxamine. These data indicated that SGNI induced a ferroptotic cell death of TNBC cells. Mechanistically, SGNI induced ferroptosis was dependent on HO-1, which promotes intracellular labile iron pool accumulation, and was alleviated by HO-1 knockdown and inhibition by tin protoporphyrin IX. In line with the in vitro data, SGNI significantly inhibited the xenograft growth of TNBC cell line MD-MB-231 in nude mice. CONCLUSION: Collectively, our study elaborates on a promising regimen for TNBC treatment through induction of ferroptosis by SGNI, a traditional Chinese patent medicine currently available in the clinic, which merits further investigation.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Ferroptose/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Ferro/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Morte Celular , Linhagem Celular Tumoral , Proliferação de Células , China , Cicloexilaminas , Feminino , Humanos , Peroxidação de Lipídeos , Medicina Tradicional Chinesa , Camundongos , Camundongos Nus , Fenilenodiaminas , Quinoxalinas , Compostos de Espiro , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Biochem Biophys Res Commun ; 551: 38-45, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33714758

RESUMO

Isocitrate dehydrogenase 1 (IDH1) mutant R132H, promoting the oncometabolite D-2-hydroxyglutarate (D2HG), is a driver mutation and an emerging therapeutic target in glioma. This study identified a novel mutant IDH1 inhibitor, WM17, by virtual screening and enzymatic confirmation. It could bind to and increase mutant IDH1 protein's thermostability in both endogenous heterozygous cells and exogenous overexpressed cells. Consequently, WM17 reversed the accumulation of D2HG and histone hypermethylation in IDH1 mutated cells. Finally, we concluded that WM17 significantly inhibited cell migration in IDH1 mutated glioma cells, although it has no apparent effect on cell proliferation. Further studies are guaranteed toward the development of WM17 as a therapeutic agent for IDH1 mutated glioma.


Assuntos
Glioma/tratamento farmacológico , Isocitrato Desidrogenase/antagonistas & inibidores , Isocitrato Desidrogenase/genética , Proteínas Mutantes/antagonistas & inibidores , Mutação , Benzenoacetamidas/farmacologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estabilidade Enzimática/efeitos dos fármacos , Glioma/enzimologia , Glioma/genética , Glioma/patologia , Histonas/metabolismo , Humanos , Imidazóis/farmacologia , Metilação/efeitos dos fármacos , Modelos Moleculares , Terapia de Alvo Molecular , Proteínas Mutantes/genética , Ligação Proteica
18.
Biomed Res Int ; 2021: 8840835, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708997

RESUMO

This study established an interpretable machine learning model to predict the severity of coronavirus disease 2019 (COVID-19) and output the most crucial deterioration factors. Clinical information, laboratory tests, and chest computed tomography (CT) scans at admission were collected. Two experienced radiologists reviewed the scans for the patterns, distribution, and CT scores of lung abnormalities. Six machine learning models were established to predict the severity of COVID-19. After parameter tuning and performance comparison, the optimal model was explained using Shapley Additive explanations to output the crucial factors. This study enrolled and classified 198 patients into mild (n = 162; 46.93 ± 14.49 years old) and severe (n = 36; 60.97 ± 15.91 years old) groups. The severe group had a higher temperature (37.42 ± 0.99°C vs. 36.75 ± 0.66°C), CT score at admission, neutrophil count, and neutrophil-to-lymphocyte ratio than the mild group. The XGBoost model ranked first among all models, with an AUC, sensitivity, and specificity of 0.924, 90.91%, and 97.96%, respectively. The early stage of chest CT, total CT score of the percentage of lung involvement, and age were the top three contributors to the prediction of the deterioration of XGBoost. A higher total score on chest CT had a more significant impact on the prediction. In conclusion, the XGBoost model to predict the severity of COVID-19 achieved excellent performance and output the essential factors in the deterioration process, which may help with early clinical intervention, improve prognosis, and reduce mortality.


Assuntos
COVID-19/diagnóstico por imagem , COVID-19/etiologia , Diagnóstico por Computador/métodos , Adulto , Idoso , Contagem de Células Sanguíneas , COVID-19/sangue , Dispneia/virologia , Feminino , Febre/virologia , Humanos , Aprendizado de Máquina , Masculino , Modelos Biológicos , Neutrófilos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
19.
Chem Soc Rev ; 50(6): 3957-3989, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33587075

RESUMO

Compartmentalization is a hallmark of living systems. Through compartmentalization, ubiquitous protein nanocages such as viral capsids, ferritin, small heat shock proteins, and DNA-binding proteins from starved cells fulfill a variety of functions, while their shell-like structures hold great promise for various applications in the field of nanomedicine and nanotechnology. However, the number and structure of natural protein nanocages are limited, and these natural protein nanocages may not be suited for a given application, which might impede their further application as nanovehicles, biotemplates or building blocks. To overcome these shortcomings, different strategies have been developed by scientists to construct artificial protein nanocages, and 1D, 2D and 3D protein arrays with protein nanocages as building blocks through genetic and chemical modification to rival the size and functionality of natural protein nanocages. This review outlines the recent advances in the field of the design and construction of artificial protein nanocages and their assemblies with higher order, summarizes the strategies for creating the assembly of protein nanocages from zero-dimension to three dimensions, and introduces their corresponding applications in the preparation of nanomaterials, electrochemistry, and drug delivery. The review will highlight the roles of both the inter-subunit/intermolecular interactions at the key interface and the protein symmetry in constructing and controlling protein nanocage assemblies with different dimensions.


Assuntos
Nanoestruturas/química , Proteínas/química , Proteínas do Capsídeo/química , Catálise , Complexos de Coordenação/química , Portadores de Fármacos/química , Ferritinas/química , Propriedades de Superfície
20.
Acta Pharmacol Sin ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608672

RESUMO

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 µM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 µM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.

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