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1.
Lancet Oncol ; 20(11): e619-e626, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31674320

RESUMO

As a result of recent, substantial capacity building, a new landscape for cancer drug trials is emerging in China. However, data on the characteristics of cancer drug trials, and how they have changed over time, are scarce. Based on clinical trials published on the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, we aimed to systematically review changes over time in clinical trials of cancer drugs in mainland China from 2009 to 2018, to provide insight on the effectiveness of the pharmaceutical industry and identify unmet clinical needs of stakeholders. A total of 1493 trials of 751 newly tested cancer drugs were initiated. Increases over time were observed for the annual number of initiated trials, newly tested drugs, and newly added leading clinical trial units, with a sharp increase after 2016. Of the 1385 trials in which cancer types were identified, solid tumours (325 [23%] trials), non-small-cell lung cancer (232 [17%]), and lymphoma (126 [9%]) were the most common. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east China (50 [41%]) and the smallest number located in southwest China (4 [3%]). The growth trends we observed illustrate the progress in and increasing capability of cancer drug research and development achieved in mainland China over the decade from 2009. The low number of clinical trials on tumours with epidemiological characteristics unique to the Chinese population and the unbalanced geographical distribution of leading clinical trial units will provide potential targets for policy makers and other stakeholders. Further research efforts should address cancers uniquely relevant to Chinese populations, globally rare cancers, and the balance between equitable drug access, efficiency, and sustainability of cancer drug research and development in mainland China.

2.
Nucleic Acids Res ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31598693

RESUMO

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. Here, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org). We identified a total of 311 571 RBPs with RBDs (corresponding to 6368 ortholog groups) and 3,651 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures, PPI-network and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for both the communities of RNA biology and cancer biology.

3.
Int J Mol Sci ; 20(20)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614930

RESUMO

The tumor microenvironment, which consists of fibroblasts, smooth muscle cells, endothelial cells, immune cells, epithelial cells, and extracellular matrices, plays a crucial role in tumor progression. Hepatic stellate cells (HSCs), a class of unique liver stromal cells, participate in immunomodulatory activities by inducing the apoptosis of effector T-cells, generation of regulatory T-cells, and development of myeloid-derived suppressor cells (MDSCs) to achieve long-term survival of islet allografts. This study provides in vitro and in vivo evidences that HSCs induce the generation of MDSCs to promote hepatocellular carcinoma (HCC) progression through interleukin (IL)-6 secretion. HSC-induced MDSCs highly expressed inducible nitric oxide synthase (iNOS) and arginase 1 mRNA and presented potent inhibitory T-cell immune responses in the tumor environment. Wild-type HSC-induced MDSCs expressed lower levels of CD40, CD86, and MHC II, and a higher level of B7-H1 surface molecules, as well as increased the production of iNOS and arginase I compared with MDSCs induced by IL-6-deficient HSCs in vitro. A murine-transplanted model of the liver tumor showed that HCCs cotransplanted with HSCs could significantly enhance the tumor area and detect more MDSCs compared with HCCs alone or HCCs cotransplanted with HSCs lacking IL-6. In conclusion, the results indicated that MDSCs are induced mainly by HSCs through IL-6 signaling and produce inhibitory enzymes to reduce T-cell immunity and then promote HCC progression within the tumor microenvironment. Therapies targeting the pathway involved in MDSC production or its immune-modulating pathways can serve as an alternative immunotherapy for HCC.

4.
Cancer Lett ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31644929

RESUMO

Immune checkpoint inhibitors against PD-1/PD-L1 yield improved survival rates of KRAS-mutant NSCLC patients, who conferred a poor prognosis without effective targeted therapy until now. Yet, the underlying association between KRAS mutations and immune responses remains unclear. We performed an integrated analysis of the data from publicly available repositories and from clinical center cohorts to explore the association between KRAS mutation status and tumor immunity-associated features, including PD-L1 expression, CD8+ tumor-infiltrating lymphocytes (TILs) and tumor mutational burden (TMB). Our results revealed that KRAS mutations are correlated with an inflammatory tumor microenvironment and tumor immunogenicity, resulting in superior patient response to PD-1/PD-L1 inhibitors. Meanwhile, three-pool analysis further confirmed that KRAS-mutant NSCLC patients show remarkable clinical benefit from anti-PD-1/PD-L1 immunotherapy. In addition, a KRAS-mutant lung adenocarcinoma mouse model was established to estimate the relative efficacy of anti-PD-L1 monoclonal antibody monotherapy or combination treatment with docetaxel versus docetaxel alone. Most surprisingly, we found that PD-L1 blockade combined with docetaxel did not promote an anti-tumor response. These findings uncover that PD-1/PD-L1 blockade monotherapy may be the optimal therapeutic schedule in NSCLC patients harboring KRAS mutations.

5.
Cancer Commun (Lond) ; 39(1): 54, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578148

RESUMO

BACKGROUND: Cancer cells reprogram metabolism for proliferation. Phosphoglycerate kinase 1 (PGK1), as a glycolytic enzyme and newly identified protein kinase, coordinates glycolysis and mitochondrial metabolism. However, the clinical significance of PGK1 expression and function in cancer progression is unclear. Here, we investigated the relationship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation. METHODS: We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets. Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation, we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types. RESULTS: The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types, respectively. In breast carcinoma, elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis. Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival (OS) in cancers of the breast, liver, lung, stomach, and esophagus and with advanced TNM stage in breast and esophageal cancers. PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver, lung, and stomach cancer. CONCLUSIONS: The elevated expression, promoter hypomethylation, and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer. PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.

6.
PLoS One ; 14(10): e0223973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618244

RESUMO

In order to address the time pattern problems in free-floating car sharing, in this paper, the authors offer a comprehensive time-series method based on deep learning theory. According to car2go booking record data in Seattle area. Firstly, influence of time and location on the free-floating car-sharing usage pattern is analyzed, which reveals an apparent doublet pattern for time and dependence usage amount on population. Then, on the basis of the long-short-term memory recurrent neural network (LSTM-RNN), hourly variation in short-term traffic characteristics including travel demand and travel distance are modeled. The results were also compared with other different statistical models, such as support vector regression (SVR), Autoregressive Integrated Moving Average model (ARIMA), single and second exponential smoothing. It showed that (LSTM-RNN) shows better performance in terms of statistical analysis and tendency precision based on limited data sample.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31522278

RESUMO

PURPOSE: Combined immunotherapy with anti-programmed cell death-ligand 1 (PD-L1) and an inhibitor of cluster of differentiation 47 (CD47) have exhibited preliminary anti-tumor effect. Our study attempted to describe the PD-L1/CD47 expression status in pulmonary sarcomatoid carcinoma (PSC), and explore its survival impact and relevance with cytotoxic T lymphocytes and macrophages infiltration. METHODS: 148 patients with PSC who underwent surgeries were retrospectively reviewed. Tissue microarrays were conducted for immunohistochemistry (IHC) of PD-L1, CD47, CD8 and CD68. RESULTS: 54 (36.5%) and 78 (52.7%) cases were positive for PD-L1 and CD47, respectively, and 36 (24.3%) of them demonstrated PD-L1/CD47 co-expression. There was a significant correlation between PD-L1 and CD47 expression (P = 0.011). The median overall survival (OS) was 22.5 months (range 0.9-102.4 months). The univariate analysis demonstrated a significantly worse OS in cases with CD47 expression (hazard ratio [HR], 1.66; 95% CI, 1.14-2.42, P = 0.008) and PD-L1/CD47 co-expression (HR, 1.75; 95% CI, 1.15-2.67, P = 0.009). The multivariate analysis demonstrated PD-L1/CD47 co-expression (HR, 1.83; 95% CI, 1.17-2.87, P = 0.008), T stage, M stage, completeness of resection and adjuvant therapy were independent prognostic factors for OS. There was a significant relevance between PD-L1 expression and PD-L1/CD47 co-expression with higher densities of CD8-positive T lymphocytes (P = 0.004, 0.012, respectively) and CD68-positive macrophages (P = 0.026, 0.034, respectively). CONCLUSION: We demonstrated the PD-L1/CD47 co-expression status in PSC. PD-L1 expression correlated with CD47 expression, and PD-L1/CD47 co-expression correlated with poorer prognosis and may serve as a predictive biomarker for combined dual-targeting immunotherapy in PSC patients.

8.
J Clin Invest ; 129(10): 4276-4289, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483290

RESUMO

BACKGROUNDAdenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.METHODSAn integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.RESULTSCompared with primary tumors, R/M tumors were enriched for alterations in key Notch (NOTCH1, 26.3% vs. 8.5%; NOTCH2, 4.6% vs. 2.3%; NOTCH3, 5.7% vs. 2.3%; NOTCH4, 3.6% vs. 0.6%) and chromatin-remodeling (KDM6A, 15.2% vs. 3.4%; KMT2C/MLL3, 14.3% vs. 4.0%; ARID1B, 14.1% vs. 4.0%) genes. TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both NOTCH1 mutations (q = 3.3 × 10-4) and MYB/MYBL1 fusions (q = 5.6 × 10-3), suggesting discrete, alternative mechanisms of tumorigenesis. This network of alterations defined 4 distinct ACC subgroups: MYB+NOTCH1+, MYB+/other, MYBWTNOTCH1+, and MYBWTTERT+. Despite low mutational load, we identified numerous samples with marked intratumoral genetic heterogeneity, including branching evolution across multiregion sequencing.CONCLUSIONThese observations collectively redefine the molecular underpinnings of ACC progression and identify further targets for precision therapies.FUNDINGAdenoid Cystic Carcinoma Research Foundation, Pershing Square Sohn Cancer Research grant, the PaineWebber Chair, Stand Up 2 Cancer, NIH R01 CA205426, the STARR Cancer Consortium, NCI R35 CA232097, the Frederick Adler Chair, Cycle for Survival, the Jayme Flowers Fund, The Sebastian Nativo Fund, NIH K08 DE024774 and R01 DE027738, and MSKCC through NIH/NCI Cancer Center Support Grant (P30 CA008748).

9.
Medicine (Baltimore) ; 98(37): e17109, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517844

RESUMO

BACKGROUND: Patients suffering from chemotherapy-induced nausea and vomiting (CINV) might have negative adherence of treatment. Acupoint therapies, including acupuncture, acupressure, acupoints injection, massage, and moxibustion, are safe medical procedures with minimal side effects for CINV, but studies about overall safety and effectiveness of acupoint therapies have not been scientifically and methodically evaluated in recent years. Evaluating the overall safety and effectiveness of acupoint therapies in patients with CINV is the purpose of this review. METHODS AND ANALYSIS: Relevant randomized controlled trials (RCTSs) are being searched in the following electronic databases: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). We will also attempt to obtain the unpublished academic data by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of the acupoint therapies for CINV patients will be searched in the databases from inception to July 2019. The primary outcomes are defined as severity, duration and frequency of nausea or vomiting, or both. The secondary outcomes are defined as any adverse events and quality of life. Performing the meta-analysis by using RevMan version 5 software. Mean difference (MD) or standardized mean difference (SMD) will express the continuous variables, while relative risk (RR) will express the categorical variables. RESULTS: The results of this review will provide a high-quality synthesis to evaluate the effectiveness and safety of acupoint therapies for CINV. CONCLUSION: This review will provide evidence to estimate whether acupoint therapies are effective interventions for CINV. DISSEMINATION: Evidence whether acupoint therapies are effective interventions for CINV will be provided by this systematic review. This knowledge will recommend better acupoint therapies and selections of acupoints which might be helpful in treating CINV. The findings of this systematic review will be disseminated via various forms of presentation and publication of the data in a journal or electronic databases. PROSPERO REGISTRATION NUMBER: CRD42019125538.


Assuntos
Terapia por Acupuntura/normas , Tratamento Farmacológico/métodos , Náusea/etiologia , Vômito/etiologia , Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Humanos , Náusea/prevenção & controle , Náusea/terapia , Vômito/prevenção & controle , Vômito/terapia
10.
Small ; 15(45): e1903410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31517439

RESUMO

Benefiting from metal-organic frameworks (MOFs) unique structural characteristics, their versatility in composition and structure has been well explored in electrochemical oxygen evolution reaction (OER) processes. Here, a ligand/ionic exchange phenomenon of MOFs is reported in alkaline solution due to their poor stability, and the active species and reaction mechanism of MOFs are revealed in the OER process. A series of mixed Ni-MOFs and Fe-MOFs are synthesized by straightforward sonication and then directly used as catalyst candidates for OER in alkaline electrolyte. It can be confirmed via ex situ transmission electron microscopic images and X-ray diffraction patterns analysis, that the bimetallic hydroxide (NiFe-LDH) is generated in 1.0 m KOH in situ and acts as protagonist for oxygen evolution. The optimized catalyst (FN-2) exhibits a lower overpotential (275 mV at a current density of 10 mA cm-2 ) and excellent long-term stability (strong current density for 100 h without fading). The revelation of the real active species of MOF materials may contribute to better understanding of the reaction mechanism.

11.
PLoS One ; 14(9): e0223101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557248

RESUMO

Research has found that preschoolers' imitation demonstrates in-group bias and is guided by behavior efficacy. However, little is known about whether children's sensitivity to behavior efficacy affects their in-group imitation. This study aimed to investigate preschoolers' imitation tendency when group preference and behavior efficacy are in conflict. Participants were 4-year-old (N = 72) and 6-year-old (N = 72) preschoolers in China. They observed two demonstrators (one in-group and one out-group) pressing two different buttons, respectively, to turn on a music box, and were then asked to try it themselves. In the experimental condition, the out-group demonstrator always succeeded, whereas the in-group demonstrator failed half the time. The results showed that more 6-year-old children imitated the less-effective behaviors of the in-group demonstrator, whereas 4-year-old children showed no such inclination. Two control conditions confirmed that children chose to imitate in-group rather than out-group members (Control 1: both in-group and out-group demonstrators succeeded all four times), and could imitate according to efficacy (Control 2: two in-group demonstrators succeeded two and four times, respectively). These results indicated that 6-year-olds faithfully followed the in-group modeled behavior, regardless of behavior efficacy. Results are discussed through the social function of in-group imitative learning.

12.
J Environ Manage ; 248: 109271, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377540

RESUMO

Algal blooms, whether they are harmful or more akin to a nuisance, do pose negative impacts on human well-being. In the province of Quebec, excessive phosphorus that contributes to the problem of cyanobacterial blooms comes mainly from non-point sources. Limited regulation on the management of this nutrient leads to its strong accumulation in soils and, combined to climate change effects, contributes to increasing the magnitude of the effects of algal blooms on humans and the environment. The presence of cyanobacteria in water has impacts on its colour, texture and odour, in addition to posing threats to the health of recreationists, as some cyanobacteria are known to release toxins during blooms. This research focuses on studying the impacts of algal bloom events on recreationists and people living close to affected waterbodies. More specifically, we explore the preferences of individuals for different ecosystem services (ES), mainly cultural ES, provided by waterbodies (i.e., recreational activities, aesthetic aspects, and ecological health). We also estimate the average willingness to pay, financed through an increase in municipal taxation, for mechanisms that would allow the resolution of this issue. To achieve these objectives, we use a choice experiment approach, enclosed in a questionnaire that was carried out in person to 252 people. Conditional logit with and without interactions, and a random parameter logit (mixed logit) are alternatively used. Results show that individuals value first their ability to perform recreational activities, followed by the ecological health of waterbodies, and the aesthetic aspects (i.e., odour and visual aspects). Interestingly, the fact that people reported taking part in fishing activities influenced the way they prioritized ES in the choice modelling exercises. Based on the most robust model, we estimate the average willingness to pay at CA$353/household per year to fund a suite of solutions aimed at improving overall water quality.


Assuntos
Cianobactérias , Ecossistema , Água Doce , Humanos , Quebeque , Água
13.
Biomed Res Int ; 2019: 3469754, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467881

RESUMO

Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.

14.
Biosens Bioelectron ; 142: 111525, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369944

RESUMO

In this work, a metallic composite with strong electrocatalytic property was designed by uniformly decorating Pt and Sn nanoparticles on the surface of TiO2 nanorods (Pt-Sn@TiO2). A detection scheme was then developed based on a dual signal amplification strategy involving the Pt-Sn@TiO2 composite and exonuclease assisted target recycling. The Pt-Sn@TiO2 composite exhibited an enhanced oxygen reduction current owing to the synergistic effect between Pt and Sn, as well as high exposure of Pt (111) crystal face. Initially, a Pt-Sn@TiO2 modified glassy carbon electrode produced an amplified electrochemical signal for the reduction of dissolved oxygen in the analyte solution. Next, a DNA with a complementary sequence to a streptomycin aptamer (cDNA) was immobilised on the Pt-Sn@TiO2 modified electrode, followed by the streptomycin aptamer that hybridised with cDNA. The corresponding oxygen reduction current was diminished by 51% attributable to the hindrance from the biomolecules. After a mixture of streptomycin and RecJf exonuclease was introduced, both the streptomycin-aptamer complex and the cDNA were cleaved from the electrode, making the Pt-Sn and Pt (111) surface available for oxygen reduction. RecJf would also release streptomycin from the streptomycin-aptamer complex, allowing it to complex again with aptamers on the electrode. This has then promoted a cyclic amplification of the oxygen reduction current by 85%, which is quantitatively related to streptomycin. Under optimal conditions, the aptasensor exhibited a linear range of 0.05-1500 nM and a limit of detection of 0.02±0.0045 nM streptomycin. The sensor was then used in the real-life sample detection of streptomycin to demonstrate its potential applications to bioanalysis.

15.
Nanoscale ; 11(32): 15147-15155, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31373342

RESUMO

Janus nanoparticles (NPs) containing two chemically distinct materials in one system are of great significance for catalysis in terms of harnessing catalytic synergies that do not exist in either component. We herein present a novel synthetic method of two Janus-type MnOx-Ag and MnOx-AgI NPs. The synthesis of Janus-type MnOx-AgI NPs is based on the oxidative nucleation and growth of Ag domains on MnO first and the subsequent iodization of Ag. A mild and non-disruptive iodization strategy is developed to yield Janus MnOx-AgI NPs, in which converting Ag to AgI domains with iodomethane (CH3I) is achieved through partial iodization. Simultaneously, Mn2+ species in the primary MnO octahedra are oxidized during the growth of Ag NPs, leading to the formation of amorphous p-type MnOx domains. Therefore, the as-resultant Janus-type MnOx-AgI NPs combining two semiconductors into an integrated nanostructure can be used as an efficient photocatalyst for visible-light-driven water oxidation. Janus MnOx-AgI NPs show an expected photocatalytic activity even in the absence of Ru(bpy)3Cl2 as an electron mediator. This intriguing synthesis may offer a new opportunity to develop asymmetric nanostructures of two semiconductors that will potentially be efficient photocatalysts for solar-driven water splitting.

16.
Eye (Lond) ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455902

RESUMO

OBJECTIVES: The purpose of this study is to assess the accuracy of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) and to explore the feasibility of applying AI-based technique to community hospital for DR screening. METHODS: Nonmydriatic fundus photos were taken for 889 diabetic patients who were screened in community hospital clinic. According to DR international classification standards, ophthalmologists and AI identified and classified these fundus photos. The sensitivity and specificity of AI automatic grading were evaluated according to ophthalmologists' grading. RESULTS: DR was detected by ophthalmologists in 143 (16.1%) participants and by AI in 145 (16.3%) participants. Among them, there were 101 (11.4%) participants diagnosed with referable diabetic retinopathy (RDR) by ophthalmologists and 103 (11.6%) by AI. The sensitivity, specificity and area under the curve (AUC) of AI for detecting DR were 90.79% (95% CI 86.4-94.1), 98.5% (95% CI 97.8-99.0) and 0.946 (95% CI 0.935-0.956), respectively. For detecting RDR, the sensitivity, specificity and AUC of AI were 91.18% (95% CI 86.4-94.7), 98.79% (95% CI 98.1-99.3) and 0.950 (95% CI 0.939-0.960), respectively. CONCLUSION: AI has high sensitivity and specificity in detecting DR and RDR, so it is feasible to carry out AI-based DR screening in outpatient clinic of community hospital.

17.
J Agric Food Chem ; 67(40): 11219-11229, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31408330

RESUMO

Peanut allergy is a major health problem worldwide. Detection of food allergens is a critical aspect of food safety. The VHH domain of single chain antibody from camelids, also known as nanobody (Nb), showed its advantages in the development of biosensors because of its high stability, small molecular size, and ease of production. However, no nanobody specific to peanut allergens has been developed. In this study, we constructed a library with random triplets (NNK) in its CDR regions of a camel nanobody backbone. We screened the library with peanut allergy Ara h 3 and obtained several candidate nanobodies. One of the promising nanobodies, Nb16 was further biochemical characterization by gel filtration, isothermal titration calorimetry (ITC), cocrystallization, and Western blot in terms of its interaction with Ara h 3. Nb16 specifically binds to peanut major allergen Ara h 3 with a dissociation constant of 400 nM. Furthermore, we obtained the Ara h 3-Nb16 complex crystals. Structure analysis shows the packing mode is completely different between the Ara h 3-Nb16 complex crystal and the native Ara h 3 crystal. Structural determination of Ara h 3-Nb16 will provide the necessary information to understand the allergenicity of this important peanut allergen. The nanobody Nb16 may have application in the development of biosensors for peanut allergen detection.


Assuntos
Antígenos de Plantas/imunologia , Arachis/imunologia , Proteínas de Armazenamento de Sementes/imunologia , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/imunologia , Sequência de Aminoácidos , Antígenos de Plantas/química , Antígenos de Plantas/genética , Arachis/química , Arachis/genética , Bacteriófagos/genética , Bacteriófagos/metabolismo , Western Blotting , Técnicas de Visualização da Superfície Celular , Proteínas de Armazenamento de Sementes/química , Proteínas de Armazenamento de Sementes/genética , Anticorpos de Domínio Único/análise
18.
Elife ; 82019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31442201

RESUMO

Gliosis defined as reactive changes of resident glia is the primary response of the central nervous system (CNS) to trauma. The proliferation and fate controls of injury-reactivated glia are essential but remain largely unexplored. In zebrafish optic tectum, we found that stab injury drove a subset of radial glia (RG) into the cell cycle, and surprisingly, proliferative RG responding to sequential injuries of the same site were distinct but overlapping, which was in agreement with stochastic cell-cycle entry. Single-cell RNA sequencing analysis and functional assays further revealed the involvement of Notch/Delta lateral inhibition in this stochastic cell-cycle entry. Furthermore, the long-term clonal analysis showed that proliferative RG were largely gliogenic. Notch inhibition of reactive RG, not dormant and proliferative RG, resulted in an increased production of neurons, which were short-lived. Our findings gain new insights into the proliferation and fate controls of injury-reactivated CNS glia in zebrafish.

19.
Angew Chem Int Ed Engl ; 58(44): 15834-15840, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31468668

RESUMO

The stability of metal nanocatalysts for electrocatalytic CO2 reduction is of key importance for practical application. We report the use of two polymeric N-heterocyclic carbenes (NHC) (polydentate and monodentate) to stabilize metal nanocatalysts (Au and Pd) for efficient CO2 electroreduction. Compared with other conventional ligands including thiols and amines, metal-carbene bonds that are stable under reductive potentials prevent the nanoclustering of nanoparticles. Au nanocatalysts modified by polymeric NHC ligands show an activity retention of 86 % after CO2 reduction at -0.9 V for 11 h, while it is less than 10 % for unmodified Au. We demonstrate that the hydrophobicity of polymer ligands and the enriched surface electron density of metal NPs through σ-donation of NHCs substantially improve the selectivity for CO2 reduction over proton.

20.
Autophagy ; : 1-14, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31462126

RESUMO

Long noncoding RNAs (lncRNAs) are proved to be critical regulators in numerous cellular processes. However, the potential involvement of lncRNAs in macroautophagy/autophagy is largely unknown. Autophagy is a highly regulated cellular degradation system, and its dysregulation is involved in many human diseases, including cancers. Here, we show that the lncRNA ZNNT1 is induced by PP242 and MTORC1 selective inhibitor rapamycin in uveal melanoma (UM) cells. Overexpression of ZNNT1 promotes autophagy by upregulating ATG12 expression, whereas knockdown of ZNNT1 attenuates PP242-induced autophagy. Overexpression of ZNNT1 inhibits tumorigenesis and the migration of UM cells, and knockdown of ATG12 can partially rescue the ZNNT1-induced inhibition of UM tumorigenesis. In summary, our study reveals that ZNNT1 acts as a potential tumor suppressor in UM by inducing autophagy. Abbreviations: ADCD: autophagy dependent cell death; ANXA2R: annexin A2 receptor; ATG12: autophagy- related 12; ATG5: autophagy -related 5; ceRNA: competing endogenous RNAs; CQ: chloroquine; iTRAQ: isobaric tags for relative and absolute quantitation; lncRNA: long noncoding RNA; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR cmplex 2; PP242: Torkinib; RACE: rapid amplification of cDNA ends; SQSTM1/p62: sequestosome 1; UM: uveal melanoma.

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