Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.782
Filtrar
1.
Adv Sci (Weinh) ; : e2102592, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719864

RESUMO

The accuracy of de novo protein structure prediction has been improved considerably in recent years, mostly due to the introduction of deep learning techniques. In this work, trRosettaX, an improved version of trRosetta for protein structure prediction is presented. The major improvement over trRosetta consists of two folds. The first is the application of a new multi-scale network, i.e., Res2Net, for improved prediction of inter-residue geometries, including distance and orientations. The second is an attention-based module to exploit multiple homologous templates to increase the accuracy further. Compared with trRosetta, trRosettaX improves the contact precision by 6% and 8% on the free modeling targets of CASP13 and CASP14, respectively. A preliminary version of trRosettaX is ranked as one of the top server groups in CASP14's blind test. Additional benchmark test on 161 targets from CAMEO (between Jun and Sep 2020) shows that trRosettaX achieves an average TM-score ≈0.8, outperforming the top groups in CAMEO. These data suggest the effectiveness of using the multi-scale network and the benefit of incorporating homologous templates into the network. The trRosettaX algorithm is incorporated into the trRosetta server since Nov 2020. The web server, the training and inference codes are available at: https://yanglab.nankai.edu.cn/trRosetta/.

2.
Cancers (Basel) ; 13(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34771481

RESUMO

Gold nanoparticles (AuNPs) were fabricated with biocompatible collagen (Col) and then conjugated with berberine (BB), denoted as Au-Col-BB, to investigate the endocytic mechanisms in Her-2 breast cancer cell line and in bovine aortic endothelial cells (BAEC). Owing to the superior biocompatibility, tunable physicochemical properties, and potential functionalization with biomolecules, AuNPs have been well studied as carriers of biomolecules for diseases and cancer therapeutics. Composites of AuNPs with biopolymer, such as fibronectin or Col, have been revealed to increase cell proliferation, migration, and differentiation. BB is a natural compound with impressive health benefits, such as lowering blood sugar and reducing weight. In addition, BB can inhibit cell proliferation by modulating cell cycle progress and autophagy, and induce cell apoptosis in vivo and in vitro. In the current research, BB was conjugated on the Col-AuNP composite ("Au-Col"). The UV-Visible spectroscopy and infrared spectroscopy confirmed the conjugation of BB on Au-Col. The particle size of the Au-Col-BB conjugate was about 227 nm, determined by dynamic light scattering. Furthermore, Au-Col-BB was less cytotoxic to BAEC vs. Her-2 cell line in terms of MTT assay and cell cycle behavior. Au-Col-BB, compared to Au-Col, showed greater cell uptake capacity and potential cellular transportation by BAEC and Her-2 using the fluorescence-conjugated Au-Col-BB. In addition, the clathrin-mediated endocytosis and cell autophagy seemed to be the favorite endocytic mechanism for the internalization of Au-Col-BB by BAEC and Her-2. Au-Col-BB significantly inhibited cell migration in Her-2, but not in BAEC. Moreover, apoptotic cascade proteins, such as Bax and p21, were expressed in Her-2 after the treatment of Au-Col-BB. The tumor suppression was examined in a model of xenograft mice treated with Au-Col-BB nanovehicles. Results demonstrated that the tumor weight was remarkably reduced by the treatment of Au-Col-BB. Altogether, the promising findings of Au-Col-BB nanocarrier on Her-2 breast cancer cell line suggest that Au-Col-BB may be a good candidate of anticancer drug for the treatment of human breast cancer.

3.
World J Gastroenterol ; 27(40): 6908-6926, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34790014

RESUMO

BACKGROUND: Hepatic stellate cells (HSCs) are the key effector cells mediating the occurrence and development of liver fibrosis, while aerobic glycolysis is an important metabolic characteristic of HSC activation. Transforming growth factor-ß1 (TGF-ß1) induces aerobic glycolysis and is a driving factor for metabolic reprogramming. The occurrence of glycolysis depends on a high glucose uptake level. Glucose transporter 1 (GLUT1) is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism, thus affecting cell proliferation and growth. However, little is known about the relationship between TGF-ß1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs. AIM: To investigate the mechanisms of action of GLUT1, TGF-ß1 and aerobic glycolysis in the process of HSC activation during liver fibrosis. METHODS: Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue. A Seahorse extracellular flux (XF) analyzer was used to examine changes in aerobic glycolytic flux, lactate production levels and glucose consumption levels in HSCs upon TGF-ß1 stimulation. The mechanism by which TGF-ß1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-ß1/mothers-against-decapentaplegic-homolog 2/3 (Smad2/3) signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. In addition, GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs. Finally, a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis. RESULTS: GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues. In addition, immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins, indicating that GLUT1 expression was related to the development of liver fibrosis. TGF-ß1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad, p38 MAPK and P13K/AKT signaling pathways. The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression. GLUT1 inhibition eliminated the effect of TGF-ß1 on HSC proliferation and migration. A GLUT1 inhibitor was administered in a mouse model of liver fibrosis, and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis. CONCLUSION: TGF-ß1 induces GLUT1 expression in HSCs, a process related to liver fibrosis progression. In vitro experiments revealed that TGF-ß1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs. In addition, in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.


Assuntos
Células Estreladas do Fígado , Fator de Crescimento Transformador beta1 , Animais , Transportador de Glucose Tipo 1 , Glicólise , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/patologia , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
4.
Front Med (Lausanne) ; 8: 772424, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790684

RESUMO

Vaccination plays an important role during the COVID-19 pandemic. Vaccine-induced thrombotic thrombocytopenia (VITT) is a major adverse effect that could be lethal. For cancer patients, cancer-related thromboembolism is another lethal complication. When cancer patients receive their COVID-19 vaccines, the following thromboembolic events will be more complicated. We presented a case recently diagnosed with pancreatic cancer, who had received the mRNA-1273 (Moderna) vaccination 12 days prior. Ischemic stroke and VITT were also diagnosed. We aggressively treated the patient with steroids, immunoglobulin, and plasma exchange. The titer of anti-platelet factor four and d-dimer level decreased, but the patient ultimately died. The complicated condition of VITT superimposed cancer-related thromboembolism was considered. To our knowledge, only one case of mRNA-1273 related VITT was reported, and this case study was the first to report a cancer patient who was diagnosed with VITT after mRNA-1273 vaccination. Therefore, when the need for vaccination among cancer patients increased under the current COVID-19 pandemic, the possible risk of VITT for cancer patients should be carefully managed. Further studies of the risk evaluation of the COVID-19 vaccine in cancer patients might be required in the future.

5.
Dalton Trans ; 50(44): 16273-16280, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34730150

RESUMO

With the aim of gaining new insight into the underlying apoptosis mechanisms and in vivo efficacy of cyclometalated Ir(III) complexes as metalodrugs, six new cyclometalated Ir(III)-quinoline complexes, [Ir(1a)(2pq)2] (2a), [Ir(1b)(2pq)2] (2b), [Ir(1c)(2pq)2] (2c), [Ir(1d)(2pq)2] (2d), [Ir(1e)(2pq)2] (2e), and [Ir(1f)(2pq)2] (2f) (2pq = 2-phenylisoquinoline), have been synthesized using 5,7-dihalo-8-hydroxylquinoline ligands (1a-1f) and [Ir(2pq)2Cl]2 precursors and characterized. Complexes 2a-2f have shown potent anticancer activity against cisplatin-resistant SK-OV-3/DDP and A549/DDP cells (IC50 = 0.11-1.83 µM), following the order 2e > 2f > 2b > 2c > 2d > 2a. Confocal microscopy images suggest that 2e and 2b could act as red-color probes for specific cell imaging and efficiently initiate apoptosis and autophagy in the mitochondria, cell cytosol, and nucleus. Overexpression of beclin1, caspase-9, cytochrome c, LC3II, and apaf-1; inhibition of p62, cyclin D1, cyclin A2, and CDK2; and a substantial rapid accumulation suggest a paraptotic mode of cell death induced by autophagy, DNA damage, and mitochondrial stress. In addition, the inhibitory rate of 2e on A549/DDP tumor growth was 64.1% at a concentration of 10.0 mg kg-1, which is clearly higher than that of cisplatin. According to the biological assay, the cyclometalated Ir(III)-quinoline complex 2e exhibited a higher anticancer effect than 2b, which may be associated with the electronic effect of the methyl group of the 1e ligand of 2e playing a key role in the mechanism.

6.
Ann Palliat Med ; 10(10): 10467-10474, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763493

RESUMO

BACKGROUND: To investigate the preventive effect of elastic stockings on deep vein thrombosis (DVT) after orthopedic surgery by literature search and meta-analysis. METHODS: PubMed, Embase and Cochrane were selected as the search database platforms to search the literature of randomized controlled trials related to elastic stockings and DVT published from 2008 to date. Revman 5.3.5 software was used for statistical analysis of the data to obtain forest and funnel plots. RESULTS: In this study, 90 studies were initially screened and 7 were finally included, covering a total of 3,116 patients. Meta-analysis showed that the 7 studies had statistical heterogeneity (I2=32%, P=0.18), so a random effect model was used. The obtained statistic was [odds ratio (OR) =0.59, 95% confidence interval (CI): (0.34, 1.03)], the statistical effect size was Z=1.84, P=0.07, and the difference was not statistically significant, so a stepwise sensitivity analysis was performed by the exclusion method. One study was excluded, and the remaining 6 showed homogeneity (I2=0%, P=0.46). They were analyzed by subgroup according to the type of operation: ankle surgery or hip and knee arthroplasty. The internal literatures of each subgroup were homogeneous: ankle surgery subgroup (I2=0%, P=0.43), hip and knee arthroplasty subgroup (I2=0%, P=0.88). Therefore, fixed effect mode analysis was used, and the effect size of elastic stockings after ankle surgery was Z=3.65, P=0.0003, while the effect size of elastic stockings in the hip and knee arthroplasty subgroup was Z=1.23, P=0.22. DISCUSSION: Elastic stockings had an obvious preventive effect on DVT in patients undergoing ankle surgery, but not in patients undergoing lumbar, knee or spinal surgery. It is necessary to combine anticoagulant drugs and other physical therapies to prevent DVT.


Assuntos
Procedimentos Ortopédicos , Trombose , Trombose Venosa , Humanos , Procedimentos Ortopédicos/efeitos adversos , Meias de Compressão , Trombose Venosa/prevenção & controle
7.
Ther Adv Med Oncol ; 13: 17588359211058255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819998

RESUMO

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is currently the standard second-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC) after previous failed gemcitabine-based therapy. This population-based study aimed to evaluate the efficacy and safety of nal-IRI + 5-FU/LV and the association of pre-emptive nal-IRI dosing with treatment outcomes in patients with PDAC. Methods: We retrospectively enrolled a total of 667 consecutive patients with PDAC who received nal-IRI plus 5-FU/LV treatment between August 2018 and November 2020 at 9 medical centers in Taiwan. Patients were allocated into groups according to pre-emptive nal-IRI dosing (⩾75%, 50-74%, <50%) for comparison of treatment efficacy and safety. Results: The median overall survival (OS) and time to treatment failure (TTF) were 5.9 months [95% confidence interval (CI), 5.3-6.5] and 2.8 months (95% CI, 2.6-3.0), respectively. The median OS was 6.5 months (95% CI, 5.7-6.7), 5.0 months (95% CI, 3.4-6.5), and 4.1 months (95% CI, 2.7-5.6), respectively, among the ⩾75%, 50-74%, and <50% pre-emptive nal-IRI dosing groups, whereas the median TTF of the three groups was 3.0 months (95% CI, 2.6-3.4), 2.6 months (95% CI, 2.3-2.9), and 1.9 months (95% CI, 1.6-2.2), respectively. Pre-emptive nal-IRI dosing <50% was an independent negative prognostic factor for OS and TTF in multivariate analyses. The most common severe adverse events were neutropenia (22.9%), anemia (21.1%), and hypokalemia (15.4%). Patients in the <50% pre-emptive nal-IRI dosing group had a significantly lower incidence of neutropenia and non-neutropenic infection than those in the other groups. Conclusion: Our results support the use of nal-IRI + 5-FU/LV as standard clinical practice for treating patients with PDAC based on this large population-based study. Our findings encourage physicians to provide adequate doses of nal-IRI in order to achieve better outcomes without compromising safety profiles.

8.
Opt Express ; 29(23): 38582-38590, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808908

RESUMO

Quantum key distribution (QKD) provides an information-theoretically secure method to share keys between legitimate users. To achieve large-scale deployment of QKD, it should be easily scalable and cost-effective. The infrastructure construction of quantum access network (QAN) expands network capacity and the integration between QKD and classical optical communications reduces the cost of channel. Here, we present a practical downstream QAN over a 10 Gbit/s Ethernet passive optical network (10G-EPON), which can support up to 64 users. In the full coexistence scheme using the single feeder fiber structure, the co-propagation of QAN and 10G-EPON signals with 9 dB attenuation is achieved over 21 km fiber, and the secure key rate for each of 16 users reaches 1.5 kbps. In the partial coexistence scheme using the dual feeder fiber structure, the combination of QAN and full-power 10G-EPON signals is achieved over 11 km with a network capacity of 64-user. The practical QAN over the 10G-EPON in our work implements an important step towards the achievement of large-scale QKD infrastructure.

9.
Laryngoscope ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821388

RESUMO

OBJECTIVES/HYPOTHESIS: To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients. STUDY DESIGN: Retrospective study. METHODS: Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups. RESULTS: The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate. CONCLUSIONS: The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission. LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

10.
Org Lett ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780172

RESUMO

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that promotes a cyclization/allylic alkylation cascade of stable α-diazo-δ-keto-esters has been developed. Highly substituted 3(2H)-furanones with a C2-quaternary center can be obtained efficiently under mild conditions via one-pot synthesis. Remarkably, this binary catalytic system shows high chemo-, regio-, and stereoselectivity and excellent tolerance to various functionalities.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34752382

RESUMO

Low-light image enhancement (LLIE) aims at improving the perception or interpretability of an image captured in an environment with poor illumination. Recent advances in this area are dominated by deep learning-based solutions, where many learning strategies, network structures, loss functions, training data, etc. have been employed. In this paper, we provide a comprehensive survey to cover various aspects ranging from algorithm taxonomy to unsolved open issues. To examine the generalization of existing methods, we propose a low-light image and video dataset, in which the images and videos are taken by different mobile phones' cameras under diverse illumination conditions. Besides, for the first time, we provide a unified online platform that covers many popular LLIE methods, of which the results can be produced through a user-friendly web interface. In addition to qualitative and quantitative evaluation of existing methods on publicly available and our proposed datasets, we also validate their performance in face detection in the dark. This survey together with the proposed dataset and online platform could serve as a reference source for future study and promote the development of this research field. The proposed platform and dataset as well as the collected methods, datasets, and evaluation metrics are publicly available.

12.
Biomedicines ; 9(11)2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34829861

RESUMO

In this study, polyethylene glycol (PEG) with hydroxyapatite (HA), with the incorporation of physical gold nanoparticles (AuNPs), was created and equipped through a surface coating technique in order to form PEG-HA-AuNP nanocomposites. The surface morphology and chemical composition were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), UV-Vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and contact angle assessment. The effects of PEG-HA-AuNP nanocomposites on the biocompatibility and biological activity of MC3T3-E1 osteoblast cells, endothelial cells (EC), macrophages (RAW 264.7), and human mesenchymal stem cells (MSCs), as well as the guiding of osteogenic differentiation, were estimated through the use of an in vitro assay. Moreover, the anti-inflammatory, biocompatibility, and endothelialization capacities were further assessed through in vivo evaluation. The PEG-HA-AuNP nanocomposites showed superior biological properties and biocompatibility capacity for cell behavior in both MC3T3-E1 cells and MSCs. These biological events surrounding the cells could be associated with the activation of adhesion, proliferation, migration, and differentiation processes on the PEG-HA-AuNP nanocomposites. Indeed, the induction of the osteogenic differentiation of MSCs by PEG-HA-AuNP nanocomposites and enhanced mineralization activity were also evidenced in this study. Moreover, from the in vivo assay, we further found that PEG-HA-AuNP nanocomposites not only facilitate the anti-immune response, as well as reducing CD86 expression, but also facilitate the endothelialization ability, as well as promoting CD31 expression, when implanted into rats subcutaneously for a period of 1 month. The current research illustrates the potential of PEG-HA-AuNP nanocomposites when used in combination with MSCs for the regeneration of bone tissue, with their nanotopography being employed as an applicable surface modification approach for the fabrication of biomaterials.

13.
Cells ; 10(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34831077

RESUMO

A nanocomposite composed of polyethylene glycol (PEG) incorporated with various concentrations (~17.4, ~43.5, ~174 ppm) of gold nanoparticles (Au) was created to investigate its biocompatibility and biological performance in vitro and in vivo. First, surface topography and chemical composition was determined through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), free radical scavenging ability, and water contact angle measurement. Additionally, the diameters of the PEG-Au nanocomposites were also evaluated through dynamic light scattering (DLS) assay. According to the results, PEG containing 43.5 ppm of Au demonstrated superior biocompatibility and biological properties for mesenchymal stem cells (MSCs), as well as superior osteogenic differentiation, adipocyte differentiation, and, particularly, neuronal differentiation. Indeed, PEG-Au 43.5 ppm induced better cell adhesion, proliferation and migration in MSCs. The higher expression of the SDF-1α/CXCR4 axis may be associated with MMPs activation and may have also promoted the differentiation capacity of MSCs. Moreover, it also prevented MSCs from apoptosis and inhibited macrophage and platelet activation, as well as reactive oxygen species (ROS) generation. Furthermore, the anti-inflammatory, biocompatibility, and endothelialization capacity of PEG-Au was measured in a rat model. After implanting the nanocomposites into rats subcutaneously for 4 weeks, PEG-Au 43.5 ppm was able to enhance the anti-immune response through inhibiting CD86 expression (M1 polarization), while also reducing leukocyte infiltration (CD45). Moreover, PEG-Au 43.5 ppm facilitated CD31 expression and anti-fibrosis ability. Above all, the PEG-Au nanocomposite was evidenced to strengthen the differentiation of MSCs into various cells, including fat, vessel, and bone tissue and, particularly, nerve cells. This research has elucidated that PEG combined with the appropriate amount of Au nanoparticles could become a potential biomaterial able to cooperate with MSCs for tissue regeneration engineering.

14.
Healthcare (Basel) ; 9(11)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34828522

RESUMO

Occupational accidents and diseases cause the loss of valuable workers and lead to high healthcare expenses. Because occupational accidents and diseases are ascribed to inadequate working conditions and work environments, they can be prevented through a well-established occupational safety and health management system, which can ensure workers' health and reduce the expense of healthcare. The study investigated the shortage of work-related occupational safety and health (OSH) measures in medium-sized manufacturing industries. This study mainly focused on qualitative interviews with 15 labor inspectors and 25 business executives from OSH participating to investigate the problems of occupational safety and health in the manufacturing industries in Taiwan. The results of a qualitative study show that the most important problems with OSH management are employers' negligence and workers' insufficient knowledge about OSH management. The research results revealed the following eighteen significant shortcomings of OSH management: employers care mostly about production profit and do not care much for OSH; OSH data collection and OSH planning are not suitable for the workplace; many managers of OSH affairs are not qualified, in terms of their professional or academic backgrounds; and the repair of workplaces' roofs often results in falling accidents, especially before or after a typhoon, because of workers' failure to use safety belts and/or to follow OSH guidelines. In order to address the shortcomings and bottlenecks, the study also presented recommendations for how to implement and revise the OSH Act and how to research and enhance OSH management. The results of this study will not only supply the Ministry of Labor (Taiwan) with data to plan the strategy of OSH management but also will allow employers and workers to improve OSH management in the workplace in order to prevent the occurrence of occupational accidents.

15.
World J Clin Cases ; 9(25): 7405-7416, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616807

RESUMO

BACKGROUND: Currently, there is a lack of sepsis screening tools that can be widely used worldwide. Pulmonary sepsis can be of sufficient concern to physicians due to their noticeable symptoms, which usually rely less on screening tools. AIM: To investigate the efficiency of the international normalized ratio (INR) for the early rapid recognition of adult nonpulmonary infectious sepsis. METHODS: This is a prospective observational study. A total of 108 sepsis patients and 106 nonsepsis patients were enrolled according to relevant inclusion and exclusion criteria. Commonly used clinical indicators, such as white blood cell, neutrophil count, lymphocyte count, neutrophil-lymphocyte count ratio (NLCR), platelets (PLT), prothrombin time, INR, activated partial thromboplastin time, and quick Sequential "Sepsis-related" Organ Failure Assessment (qSOFA) scores were recorded within 24 h after admission. The diagnostic performances of these clinical indicators were analyzed and compared through multivariate logistic regression analysis, Spearman correlation, and receiver operating characteristic curve analysis. RESULTS: The INR value of the sepsis group was significantly higher than that of the nonsepsis group. INR has superior diagnostic efficacy for sepsis, with an area under the curve value of 0.918, when those preexisting diseases which significantly affect coagulation function were excluded. The diagnostic efficacy of the INR was more significant than that of NLCR, PLT, and qSOFA (P < 0.05). Moreover, INR levels of 1.17, 1.20, and 1.22 could be used to categorize the relative risk of nonpulmonary infections sepsis into three categories: low, medium and high risk, respectively. CONCLUSION: The INR is a promising and easily available biomarker for diagnosis, and it can be used as one of the indicators for early screening of adult nonpulmonary infectious sepsis. When its value is higher than the optimal cutoff value (1.22), high vigilance is required for adult nonpulmonary infectious sepsis.

16.
Med Res Rev ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633088

RESUMO

Bromodomain-containing protein 4 (BRD4), as the most studied member of the bromodomain and extra-terminal (BET) family, is a chromatin reader protein interpreting epigenetic codes through binding to acetylated histones and non-histone proteins, thereby regulating diverse cellular processes including cell cycle, cell differentiation, and cell proliferation. As a promising drug target, BRD4 function is closely related to cancer, inflammation, cardiovascular disease, and liver fibrosis. Currently, clinical resistance to BET inhibitors has limited their applications but synergistic antitumor effects have been observed when used in combination with other tumor inhibitors targeting additional cellular components such as PLK1, HDAC, CDK, and PARP1. Therefore, designing dual-target inhibitors of BET bromodomains is a rational strategy in cancer treatment to increase potency and reduce drug resistance. This review summarizes the protein structures and biological functions of BRD4 and discusses recent advances of dual BET inhibitors from a medicinal chemistry perspective. We also discuss the current design and discovery strategies for dual BET inhibitors, providing insight into potential discovery of additional dual-target BET inhibitors.

17.
Chemistry ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613641

RESUMO

We report the synthesis of two new acyclic sulfated acyclic CB[n]-type receptors (TriM0 and Me4 TetM0) and investigations of their binding properties toward a panel of drugs of abuse (1-13) by a combination of 1 H NMR spectroscopy and isothermal titration calorimetry. TetM0 is the most potent receptor with Ka ≥106  M-1 toward methamphetamine, fentanyl, MDMA and mephedrone. TetM0 is not cytotoxic toward HepG2 and HEK 293 cells below 100 µM according to MTS metabolic and adenylate kinase release assays and is well tolerated in vivo when dosed at 46 mg kg-1 . TetM0 does not inhibit the hERG ion channel and is not mutagenic based on the Ames fluctuation test. Finally, in vivo efficacy studies show that the hyperlocomotion of mice treated with methamphetamine can be greatly reduced by treatment with TetM0 up to 5 minutes later. TetM0 has potential as a broad spectrum in vivo sequestrant for drugs of abuse.

18.
IEEE Trans Image Process ; 30: 8540-8552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618672

RESUMO

Extracting roads from satellite imagery is a promising approach to update the dynamic changes of road networks efficiently and timely. However, it is challenging due to the occlusions caused by other objects and the complex traffic environment, the pixel-based methods often generate fragmented roads and fail to predict topological correctness. In this paper, motivated by the road shapes and connections in the graph network, we propose a connectivity attention network (CoANet) to jointly learn the segmentation and pair-wise dependencies. Since the strip convolution is more aligned with the shape of roads, which are long-span, narrow, and distributed continuously. We develop a strip convolution module (SCM) that leverages four strip convolutions to capture long-range context information from different directions and avoid interference from irrelevant regions. Besides, considering the occlusions in road regions caused by buildings and trees, a connectivity attention module (CoA) is proposed to explore the relationship between neighboring pixels. The CoA module incorporates the graphical information and enables the connectivity of roads are better preserved. Extensive experiments on the popular benchmarks (SpaceNet and DeepGlobe datasets) demonstrate that our proposed CoANet establishes new state-of-the-art results. The source code will be made publicly available at: https://mmcheng.net/coanet/.

19.
Ther Adv Endocrinol Metab ; 12: 20420188211049615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676065

RESUMO

Objective: MicroRNAs (miRNAs) regulate gene expression and are involved in diabetic kidney disease (DKD) pathogenesis. We investigated circulating miRNA-194 levels as a biomarker of DKD prevalence and incidence, and the relationship between miRNA-194 and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). Methods: We recruited 136 type-2 diabetes mellitus (T2DM) patients at the First People's Hospital of Lianyungang and 127 healthy individuals. Circulating miRNA-194 and CHOP levels were measured using quantitative reverse transcription qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Anthropometric and biochemistry measurements were also made. Results: T2DM patients showed higher circulating miRNA-194 (p = 0.029) and lower circulating CHOP (p < 0.001) levels than controls. Circulating miRNA-194 levels were significantly higher in T2DM patients with a microalbumin/creatinine ratio (UmALB/Cr) ⩾ 300 mg/g (p < 0.001). In addition, there were significant intergroup differences in the circulating CHOP concentrations (p = 0.005). Bivariate analysis revealed that circulating miR-194 levels were negatively correlated with alpha-fetoprotein and CHOP levels (r = -0.222, -0.301; p = 0.018, 0.001, respectively), but positively correlated with fasting glucose, UmALB/Cr, Cr, Cystatin C, quantitative insulin check index (QUICKI) (r = 0.193, 0.446, 0.260, 0.339, and 0.250, respectively; p = 0.036, <0.001, 0.005, <0.001, and 0.006, respectively), particularly UmALB/Cr and Cystatin C (p < 0.001). Logistic regression analysis after adjusting for covariates associated with UmALB/Cr identified duration of T2DM, systolic blood pressure, Cr, estimated glomerular filtration rate, and waist circumference as independent factors associated with T2DM patients with UmALB/Cr > 300 (p = 0.030, 0.013, <0.001, <0.001, and 0.031, respectively). Conclusion: Circulating miRNA-194 levels could be a novel biomarker for DKD.

20.
Front Oncol ; 11: 609314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660250

RESUMO

Aim: The aim of our study was to investigate the prognostic value of preoperative advanced lung cancer inflammation index (ALI) and to establish prognostic nomograms for the prediction of survival outcomes in patients with oral cavity squamous cell carcinoma (OSCC). Materials and Methods: A total of 372 patients who received primary curative surgery for OSCC during 2008-2017 at a tertiary referral center were enrolled. We used the receiver operating characteristic curve to determine the optimal cutoff point of ALI. Through a Cox proportional hazards model and Kaplan-Meier analysis, we elucidated the ALI-overall survival (OS) and ALI-disease-free survival (DFS) associations. Prognostic nomograms based on ALI and the results of multivariate analysis were created to predict the OS and DFS. We used the concordance indices (C-indices) and calibration plots to assess the discriminatory and predictive ability. Results: The results revealed that the ALI cutoff was 33.6, and 105 and 267 patients had ALI values of <33.6 and ≥33.6, respectively. ALI < 33.6 significantly indicated lower OS (44.0% vs. 80.1%, p < 0.001) and DFS (33.6% vs. 62.8%; p < 0.001). In multivariate analysis, ALI < 33.6 was independently associated with poor OS and DFS (both p < 0.001). The C-indices of established nomograms were 0.773 and 0.674 for OS and DFS, respectively; moreover, the calibration plots revealed good consistency between nomogram-predicted and actual observed OS and DFS. Conclusion: ALI is a promising prognostic biomarker in patients undergoing primary surgery for OSCC; moreover, ALI-based nomograms may be a useful prognostic tool for individualized OS and DFS estimations.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...