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1.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2151-2157, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495565

RESUMO

To investigate the inhibitory effects of two xanthone compounds, 1-hydroxy-2,3,4,8-4 methoxy xanthone(here in after referred to as Fr15) and 1-hydroxy-2,3,4,6-4 methoxy xanthone(here in after referred to as Fr17), on the proliferation of hepatocellular carcinoma cells HepG2, and to further investigate their mechanism in combination with transcriptomics. Cell counting was used to detect the effects of two kinds of xanthone compounds Fr15 and Fr17(0, 0.03, 0.15, 0.3 mmoL·L~(-1)) on the proliferation of HepG2 cells; the effects of the two compounds Fr15 and Fr17 on HepG2 cell cycle were detected by flow cytometry; the changes of autophagosomes count in cells were observed under fluorescence microscope; the expression of autophagy marker proteins autophagy marker proteins SQSTM 1(p62) and microtubule associated protein 1 light chain 3 Ⅰ/Ⅱ(LC3 Ⅰ/Ⅱ) in the cells was detected by Western blot; the differentially expressed genes between the control group and the experimental group were analyzed by RNA-seq transcriptome sequencing; qRT-PCR was used to verify the differentially expressed genes in sequencing. The results showed that compounds Fr15 and Fr17 inhibited the proliferation of HepG2 cells with the increase of drug concentration and time. Flow cytometry showed that compounds Fr15 and Fr17 had little effect on HepG2 cell cycle. Fluorescence microscopy results showed that the number of autophagosomes in cells increased with the increase of drug concentration. Western blot showed that the expression of p62 protein was decreased and the expression of LC3-Ⅱ protein was significantly increased after drug addition. The results of RNA sequencing showed that 26 102 and 52 351 differentially expressed genes were obtained in Fr15 and Fr17 respectively. Analysis of KEGG showed that drug treatment had a great effect on autophagy pathway. qRT-PCR verified that 6 up-regulated genes were related to autophagy, and their trend was consis-tent with sequencing results, where all 6 genes showed an up-regulated trend. Two xanthone compounds Fr15 and Fr17 may inhibit proliferation of HepG2 cells by inducing autophagy.

2.
Inorg Chem ; 59(13): 9177-9187, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32447953

RESUMO

By taking advantage of the efficient Förster resonance energy transfer (FRET) between near-infrared (NIR)-responsive lanthanide-doped upconversion nanoparticles (UCNPs) and Fenton reagent ferrocenyl compounds (Fc), a series of Fc-UCNPs was designed by functionalizing NaYF4:Yb,Tm nanoparticles with Fc1-Fc5 via surface-coordination chemistry. Fc-UCNP-Lipo nanosystems were then constructed by encapsulating Fc-UCNP inside liposomes for efficient delivery. Fc-UCNP can effectively release ·OH via a NIR-promoted Fenton-like reaction. In vitro and in vivo studies of Fc1-UCNP-Lipo confirmed the preferential accumulation in a tumor site followed by an enhanced uptake of cancer cells. After cellular internalization, the released Fc1-UCNP can effectively promote ·OH generation for tumor growth suppression. Such a Fc1-UCNP-Lipo nanosystem exhibits advantages such as easy fabrication, low drug dosage, and no ferrous ion release.

3.
Molecules ; 25(9)2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357459

RESUMO

A short self-assembly peptide A6K (H2N-AAAAAAK-OH) with unmodified N- and C-terminus was designed, and the charge distribution model of this short peptide at different pH was established by computer simulation. The pH of the solution was adjusted according to the model and the corresponding self-assembled structure was observed using a transmission electron microscope (TEM). As the pH changes, the peptide will assemble into blocks or nanoribbons, which indicates that the A6K peptide is a pH-responsive peptide. Circular dichroism (CD) and molecular dynamics (MD) simulation showed that the block structure was formed by random coils, while the increase in ß-turn content contributes to the formation of intact nanoribbons. A reasonable explanation of the self-assembling structure was made according to the electrostatic distribution model and the effect of electrostatic interaction on self-assembly was investigated. This study laid the foundation for further design of nanomaterials based on pH-responsive peptides.

4.
Environ Toxicol ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32270919

RESUMO

Long noncoding RNA (lncRNA) AC026904.1 has been confirmed to be necessary for breast cancer metastasis. This work aims to investigate the effects of lncRNA AC026904.1 on lung cancer metastasis. We found that lncRNA AC026904.1 displayed a higher level in metastatic lung cancer tissues than adjacent tissues and nonmetastatic lung cancer tissues, and lung cancer cells treated with TGF-ß. The expression of AC026904.1 was increased by the non-canonical TGF-ß signaling. Additionally, AC026904.1 acts as an enhancer of the key metastatic factor Slug in the nucleus. This AC026904.1/Slug axis is necessary for TGF-ß-mediated migration and epithelial-mesenchymal transition in lung cancer cells. This work firstly uncovers that AC026904.1 increases Slug expression at transcriptional level and subsequently plays critical effects in lung cancer metastasis, providing novel evidences that AC026904.1 holds great potential to be used as a marker for metastatic lung cancer.

5.
J Ethnopharmacol ; 254: 112737, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32147480

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tongnao Decoction (TND) is a Chinese decoction approved and used in Jiangsu Province Hospital for the treatment of ischemic stroke. It shows conclusive efficiency in the improvement of neurologic impairment and activities of daily living of the patients. AIM OF THE STUDY: Recently, angiogenesis has been recognized as a potential therapeutic strategy for treating cerebral ischemia. This study was aimed to provide comprehensive evidence for the pro-angiogenic effect of TND and characterize the underlying mechanism. MATERIALS AND METHODS: We firstly established the chemical fingerprinting of TND. Then, the in vitro pro-angiogenic activities of TND were tested on human umbilical vein endothelial cells (HUVECs) through cell viability, wound healing and tube formation assays. The in vivo pro-angiogenic effects were evaluated on transgenic zebrafish embryos [Tg (fli-1: EGFP)] through the formation of intersegmental vessels (ISVs), subintestinal vessels (SIVs) and central arteries (CtAs). Lastly, the potential mechanisms of TND were analyzed by a blocking assay with eight pathways-specific kinase inhibitors. RESULTS: TND promoted the proliferation, migration and tube formation of HUVECs. TND also rescued the impairment of ISVs, SIVs and CtAs caused by VRI in a dose-dependent manner in zebrafish embryos. TND could activate vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) and Raf - mitogen-activated protein kinase1/2 (MEK1/2) - extracellular regulated kinase 1/2 (ERK1/2) signaling pathways. CONCLUSION: Our study firstly demonstrated the pro-angiogenic activities of TND. Our work provided evidences for the clinical usage of TND in restoring neurovascular function through promoting angiogenesis in the ischemic cerebral microvascular.

6.
Environ Res ; 184: 109368, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32192990

RESUMO

Large areas of mainland China have been suffering frequently from heavy haze pollution during the past years, which feature high concentrations of fine particulate matter (PM2.5, particulate matters with aerodynamic diameters less than 2.5 µm) and low visibility. Moreover, these areas manifested strong regional complex pollution characteristics, particularly in North China including Beijing and the five surrounding provinces (BSFP). In this study, by using the localized comprehensive emission inventory of BSFP region in 2012 as an input, the Comprehensive Air Quality Model with Extensions-Particulate Matter Source Apportionment Technology (CAMx/PSAT) was used to assess the seasonal variations and source apportionment of PM2.5 in the highly polluted BSFP region, with a specific focus on the sectoral and sub-regional contributions to PM2.5 in Beijing during winter and summer. Results showed that the PM2.5 concentrations of BSFP region was higher in winter than that in summer. And the heavily polluted area in BSFP region shrinked noticeably in summer, compared with winter. As for source apportionment of PM2.5, residential and remaining industrial sectors constituted the top two sources of PM2.5 mass concentrations in Beijing. In addition, agricultural source represented a major contributor to ammonium, whereas transportation and power sectors constituted major sources to nitrates. In terms of contributions from sub-regions, the local sources ranked as the dominant contributors to PM2.5 in Beijing, while the main external contributions originated from the surrounding areas, such as Hebei and Shandong. Results of daily source apportionment to PM2.5 in Beijing showed that sub-regional long-distance transport became stronger when haze pollution was severe, in which contribution from remaining industrial sector would be higher than that of other periods. The results will allow for an improved understanding of the causes and origins of heavy regional PM2.5 pollution, and thus will benefit the development of effective joint control policies and identification of key polluting emission categories in North China and ultimately serve as references for other highly polluted megacities in the world.

7.
Sci Total Environ ; 720: 137541, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32145625

RESUMO

Farmland soil contamination of heavy metal(loid)s (HM) derived from smelting activities is a global concern, owing to its potential threat for human health through food chain. This study aims to evaluate total contents and bioavailability of HMs (Pb, Zn, Tl, Cd, Cu, As, Ag, Co, Cr and Ni) in farmland soils distributed over ten different villages from a former artisanal zinc smelting area in the northwest Guizhou province, China. The results showed that most of the studied soils still exhibited exceptionally high enrichment of Pb, Zn, Cd and As. High levels of bioavailable HMs were also observed in some samples, which may enter the human food chain through agricultural activities. Further analyses by Scanning Transmission Electron Microscopy - Energy Dispersive Spectroscopy (STEM-EDS), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) showed the presence of Zn smelting by-products such as Fe oxides, ZnO and PbSO4 even in nanoscale particles retained by the soils. Elemental mapping by EDS confirmed a close association of the studied HMs with the smelting waste particles. All these results signify that high levels of HM-contamination from historical artisanal zinc smelting activities still persist and threaten the health of local residents, despite the fact that the major industrial-derived-contamination period ended >15 years ago. Our findings highlight pivotal concerns in similar artisanal-smelting-affected farmland soils of suspected contamination, due to less-expected toxic elements such as Tl, which may cause high ecological health risks.

8.
Phys Rev Lett ; 124(1): 017002, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31976681

RESUMO

We show that a random interacting model exhibits solvable non-Fermi-liquid behavior and exotic pairing behavior. This model, dubbed as the Yukawa-SYK model, describes the random Yukawa coupling between M quantum dots each hosting N flavors of fermions and N^{2} bosons that self-tune to criticality at low energies. The diagrammatic expansion is controlled by 1/MN, and the results become exact in a large-M, large-N limit. We find that pairing only develops within a region of the (M,N) plane-even though the pairing interaction is strongly attractive, the incoherence of the fermions can spoil the forming of Cooper pairs, rendering the system a non-Fermi liquid down to zero temperature. By solving the Eliashberg equation and the renormalization group equation, we show that the transition into the pairing phase exhibits Kosterlitz-Thouless quantum-critical behavior.

9.
Chemosphere ; 239: 124775, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31521931

RESUMO

Enriched levels of thallium (Tl) in the environment are not only derived from anthropogenic sources but also have potential natural origins owing to Tl-rich sulphide mineralization. However, little is known regarding the geochemical fractionations of Tl in contaminated soils from geogenic sources. This study aims to reveal the Tl geochemical fractionations in different types of soils from a large-scale independent Tl mine in southwestern China, via a modified Institute for Reference Materials and Measurement (IRMM) sequential extraction (four-step) scheme. The results revealed that a large percentage of Tl was related to the labile portions (including reducible, weak-acid-exchangeable, and oxidizable fraction) of the soils (68.8-367 mg kg-1). Further analyses by Scanning Transmission Electron Microscopy-Energy Dispersive X-ray Spectrometer (STEM-EDS) found that Tl mainly existed in the Fe-containing minerals (such as jarosite and hematite) with fine particles (∼1 µm). These results highlight that, apart from the anthropogenically induced Tl pollution, the naturally occurring Tl contamination in soils may also pose significant risks to human health and ecological safety. Owing to the relatively high mobility and bioavailability of Tl in the labile fractions, it is important to understand geochemical fractionations of this element for alleviating Tl pollution and effective management of naturally occurring Tl contaminated soils.


Assuntos
Poluentes do Solo/química , Tálio/química , Fracionamento Químico , China , Monitoramento Ambiental/métodos , Compostos Férricos/química , Humanos , Mercúrio/análise , Microscopia Eletrônica de Transmissão e Varredura , Solo/química , Poluentes do Solo/análise , Espectrometria por Raios X , Sulfatos/química , Sulfetos/análise , Tálio/análise
10.
Arch Oral Biol ; 109: 104570, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568992

RESUMO

OBJECTIVE: The aim of this study is to investigate the effects of 17ß-Estradiol (E2) at different concentrations combined with cyclical compressive stress on the proliferation and differentiation of mandibular condylar chondrocytes (MCCs). DESIGN: MCCs, isolated from female Sprague-Dawley rats, were exposed to E2 at different concentration, cyclical compressive stress or the combination, effects of which on MCCs proliferation and differentiation were detected. RESULTS: E2 at physiological concentration (10-9 mol/L) has lower proliferative effects on MCCs, compared with non-physiological concentration (10-12 mol/L or 10-6 mol/L). For MCCs differentiation, effects of E2 at different concentration are totally opposite: E2 at 10-9 mol/L promotes MCCs differentiation, but at 10-12 mol/L or 10-6 mol/L, it inhibits MCCs differentiation. When combined with E2 at 10-9 mol/L, cyclical compressive stress shows synergistic effect on proliferation and differentiation. However, when combined with E2 at 10-12 mol/L or 10-6 mol/L cyclical compressive stress reverses the inhibition in MCCs differentiation provoked by E2 at 10-12 mol/L or 10-6 mol/L. CONCLUSION: Effects of E2 combined with cyclical compressive stress on MCCs proliferation and differentiation are different, which suggests that orthodontist should take fully consideration of the levels of E2 and adopt comprehensive strategies, so as to achieve better orthodontic effect.


Assuntos
Condrócitos/citologia , Estradiol/farmacologia , Côndilo Mandibular/citologia , Pressão , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Ratos , Ratos Sprague-Dawley
11.
Am J Clin Pathol ; 153(1): 126-130, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585003

RESUMO

OBJECTIVES: Tuberculosis meningitis (TBM) is one of the most severe forms of tuberculosis. However, TBM diagnosis is quite challenging due to nonspecific clinical presentation and the paucity of the pathogen in cerebrospinal fluid (CSF) samples. In this study, we report a new method for detecting cell-free Mycobacterium tuberculosis DNA (cf-TB) in CSF and evaluate its clinical value for TBM diagnosis. METHODS: Of 68 patients prospectively recruited, 46 were diagnosed as having TBM and 22 as non-TBM. We compared the cf-TB method with CSF smear microscopy, mycobacterial culture, and the Xpert MTB/RIF assay (Xpert) using the consensus case definition for TBM proposed in 2009 as a reference standard. RESULTS: The sensitivity of the cf-TB test was 56.5% (26/46) in patients with TBM, and it was significantly higher than other methods: microscopy (2.2%, 1/46; P < .001), mycobacterial culture (13.0%, 6/46; P < .001), and Xpert (23.9%, 11/46; P = .001). For specificity, none of the four methods reported false-positive results in the non-TBM group. CONCLUSIONS: The new method detecting cell-free M tuberculosis DNA in CSF is rapid and accurate for diagnosis of TBM and easily incorporated into regular laboratory tests.


Assuntos
Ácidos Nucleicos Livres/líquido cefalorraquidiano , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/diagnóstico , Adolescente , Adulto , DNA Bacteriano/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/microbiologia , Tuberculose Meníngea/patologia , Adulto Jovem
12.
Nano Lett ; 19(12): 8461-8468, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31671267

RESUMO

Electroreduction of CO2 represents a promising solution for addressing the global challenges in energy and sustainability. This reaction is highly sensitive to the surface structure of electrocatalysts and the local electrochemical environment. We have investigated the effect of Cu nanoparticle shape on the electrocatalysis of CO2 reduction by using gas-diffusion electrodes (GDEs) and flowing alkaline catholytes. Cu nanocubes of ∼70 nm in edge length are synthesized with {100} facets preferentially exposed on the surface. They are demonstrated to possess substantially enhanced catalytic activity and selectivity for CO2 reduction, compared to Cu nanospheres of similar particle sizes. The electrocatalytic performance was further found to be dependent on the concentration of electrolyte (KOH). The Cu nanocubes reach a Faradaic efficiency of 60% and a partial current density of 144 mA/cm2 toward ethylene (C2H4) production, with the catalytic enhancement being attributable to a combination of surface structure and electrolyte alkalinity effects.

13.
Nano Lett ; 19(12): 9154-9159, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31738851

RESUMO

The local structure and geometry of catalytic interfaces can influence the selectivity of chemical reactions. Selectivity is often critical for the practical realization of reactions such as the electroreduction of carbon dioxide (CO2). Previously developed strategies to manipulate the structure and geometry of catalysts for electroreduction of CO2 involve complex processes or fail to efficiently alter the selectivity. Here, using a prestrained polymer, we uniaxially and biaxially compress a 60 nm gold film to form a nano-folded electrocatalyst for CO2 reduction. We observe two kinds of folds and can tune the ratio of loose to tight folds by varying the extent of prestrain in the polymer. We characterize the nano-folded catalysts using X-ray diffraction, scanning, and transmission electron microscopy. We observe grain reorientation and coarsening in the nano-folded gold catalysts. We measure an enhancement of Faradaic efficiency for carbon monoxide formation with the biaxially compressed nano-folded catalyst by a factor of about nine as compared to the flat catalyst (up to 87.4%). We rationalize this observation by noting that an increase of the local pH in the tight folds of the catalyst outweighs the effects of alterations in grain characteristics. Together, our studies demonstrate that nano-folded geometries can significantly alter grain characteristics, mass transport, and catalytic performance.

14.
Front Genet ; 10: 869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620171

RESUMO

Introduction: Leukocyte immunoglobulin-like receptor A3 (LILRA3) belongs to the LILR family with unique feature of a 6.7-kb deletion variation among individuals. Frequencies of the 6.7-kb deletion vary widely across populations, but so far it has not been carefully investigated among Han Chinese subpopulations. Furthermore, we previously identified the non-deleted (functional) LILRA3 as a novel genetic risk for multiple autoimmune diseases. The current study aimed to investigate (i) whether frequencies of the LILRA3 6.7-kb deletion differ within Han Chinese subpopulations and (ii) whether the functional LILRA3 is a novel genetic risk for ankylosing spondylitis (AS). Methods: The LILRA3 6.7-kb deletion was genotyped in two independent cohorts, including 1,567 subjects from Shenzhen Hospital and 2,507 subjects from People's Hospital of Peking University. Frequencies of the 6.7-kb deletion were first investigated in combined healthy cohort according to the Chinese administrative district divisions. Association analyses were performed on whole dataset and subsets according to the geographic regions. Impact of the functional LILRA3 on AS disease activity was evaluated. Results: Frequencies of LILRA3 6.7-kb deletion were highly differentiated within Han Chinese subpopulations, being gradually decreased from Northeast (80.6%) to South (47.4%). Functional LILRA3 seemed to be a strong genetic risk in susceptibility to AS under almost all the alternative genetic models, if the study subjects were not geographically stratified. However, stratification analysis revealed that the functional LILRA3 was consistently associated with AS susceptibility mainly in Northern Han subgroup under the alternative genetic models, but not in Central and Southern Hans. Functional LILRA3 conferred an increased disease activity in AS patients (P < 0.0001 both for CRP and ESR, and P = 0.003 for BASDAI). Conclusions: The present study is the first to report that the frequencies of LILRA3 6.7-kb deletion vary among Chinese Hans across geographic regions. The functional LILRA3 is associated with AS susceptibility mainly in Northern Han, but not in Central and Southern Han subgroups. Our finding provides new evidence that LILRA3 is a common genetic risk for multiple autoimmune diseases and highlights the genetic differentiation among different ethnicities, even within the subpopulations of an ethnic group.

15.
JAMA Oncol ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31621801

RESUMO

Importance: Adjuvant chemotherapy in patients with stage III colon cancer prevents recurrence by eradicating minimal residual disease. However, which patients remain at high risk of recurrence after completing standard adjuvant treatment cannot currently be determined. Postsurgical circulating tumor DNA (ctDNA) analysis can detect minimal residual disease and is associated with recurrence in colorectal cancers. Objective: To determine whether serial postsurgical and postchemotherapy ctDNA analysis could provide a real-time indication of adjuvant therapy efficacy in stage III colon cancer. Design, Setting, and Participants: This multicenter, Australian, population-based cohort biomarker study recruited 100 consecutive patients with newly diagnosed stage III colon cancer planned for 24 weeks of adjuvant chemotherapy from November 1, 2014, through May 31, 2017. Patients with another malignant neoplasm diagnosed within the last 3 years were excluded. Median duration of follow-up was 28.9 months (range, 11.6-46.4 months). Physicians were blinded to ctDNA results. Data were analyzed from December 10, 2018, through June 23, 2019. Exposures: Serial plasma samples were collected after surgery and after chemotherapy. Somatic mutations in individual patients' tumors were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. Personalized assays were designed to quantify ctDNA. Main Outcomes and Measures: Detection of ctDNA and recurrence-free interval (RFI). Results: After 4 exclusions, 96 eligible patients were eligible; median patient age was 64 years (range, 26-82 years); 49 (51%) were men. At least 1 somatic mutation was identified in the tumor tissue of all 96 evaluable patients. Circulating tumor DNA was detectable in 20 of 96 (21%) postsurgical samples and was associated with inferior recurrence-free survival (hazard ratio [HR], 3.8; 95% CI, 2.4-21.0; P < .001). Circulating tumor DNA was detectable in 15 of 88 (17%) postchemotherapy samples. The estimated 3-year RFI was 30% when ctDNA was detectable after chemotherapy and 77% when ctDNA was undetectable (HR, 6.8; 95% CI, 11.0-157.0; P < .001). Postsurgical ctDNA status remained independently associated with RFI after adjusting for known clinicopathologic risk factors (HR, 7.5; 95% CI, 3.5-16.1; P < .001). Conclusions and Relevance: Results suggest that ctDNA analysis after surgery is a promising prognostic marker in stage III colon cancer. Postchemotherapy ctDNA analysis may define a patient subset that remains at high risk of recurrence despite completing standard adjuvant treatment. This high-risk population presents a unique opportunity to explore additional therapeutic approaches.

16.
Sensors (Basel) ; 19(20)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658684

RESUMO

As one of the information industry's future development directions, the Internet of Things (IoT) has been widely used. In order to reduce the pressure on the network caused by the long distance between the processing platform and the terminal, edge computing provides a new paradigm for IoT applications. In many scenarios, the IoT devices are distributed in remote areas or extreme terrain and cannot be accessed directly through the terrestrial network, and data transmission can only be achieved via satellite. However, traditional satellites are highly customized, and on-board resources are designed for specific applications rather than universal computing. Therefore, we propose to transform the traditional satellite into a space edge computing node. It can dynamically load software in orbit, flexibly share on-board resources, and provide services coordinated with the cloud. The corresponding hardware structure and software architecture of the satellite is presented. Through the modeling analysis and simulation experiments of the application scenarios, the results show that the space edge computing system takes less time and consumes less energy than the traditional satellite constellation. The quality of service is mainly related to the number of satellites, satellite performance, and task offloading strategy.

17.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640203

RESUMO

The blockade of the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a critical role in cancer immunotherapy by reducing the immune escape. Five monoclonal antibodies that antagonized PD-1/PD-L1 interaction have been approved by the Food and Drug Administration (FDA) and marketed as immunotherapy for cancer treatment. However, some weaknesses of antibodies, such as high cost, low stability, poor amenability for oral administration, and immunogenicity, should not be overlooked. To overcome these disadvantages, small-molecule inhibitors targeting PD-L1 were developed. In the present work, we applied in silico and in vitro approaches to develop short peptides targeting PD-1 as chemical probes for the inhibition of PD-1-PD-L1 interaction. We first predicted the potential binding pocket on PD-1/PD-L1 protein-protein interface (PPI). Sequentially, we carried out virtual screening against our in-house peptide library to identify potential ligands. WANG-003, WANG-004, and WANG-005, three of our in-house peptides, were predicted to bind to PD-1 with promising docking scores. Next, we conducted molecular docking and molecular dynamics (MD) simulation for the further analysis of interactions between our peptides and PD-1. Finally, we evaluated the affinity between peptides and PD-1 by surface plasmon resonance (SPR) binding technology. The present study provides a new perspective for the development of PD-1 inhibitors that disrupt PD-1-PD-L1 interactions. These promising peptides have the potential to be utilized as a novel chemical probe for further studies, as well as providing a foundation for further designs of potent small-molecule inhibitors targeting PD-1.


Assuntos
Receptor de Morte Celular Programada 1/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/síntese química , Simulação por Computador , Humanos , Conformação Molecular , Simulação de Dinâmica Molecular , Receptor de Morte Celular Programada 1/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Ressonância de Plasmônio de Superfície
19.
J Am Chem Soc ; 141(42): 16635-16642, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31509393

RESUMO

Alloying is an important strategy for the design of catalytic materials beyond pure metals. The conventional alloy catalysts however lack precise control over the local atomic structures of active sites. Here we report on an investigation of the active-site ensemble effect in bimetallic Pd-Au electrocatalysts for CO2 reduction. A series of Pd@Au electrocatalysts are synthesized by decorating Au nanoparticles with Pd of controlled doses, giving rise to bimetallic surfaces containing Pd ensembles of various sizes. Their catalytic activity for electroreduction of CO2 to CO exhibits a nonlinear behavior in dependence of the Pd content, which is attributed to the variation of Pd ensemble size and the corresponding tuning of adsorption properties. Density functional theory calculations reveal that the Pd@Au electrocatalysts with atomically dispersed Pd sites possess lower energy barriers for activation of CO2 than pure Au and are also less poisoned by strongly binding *CO intermediates than pure Pd, with an intermediate ensemble size of active sites, such as Pd dimers, giving rise to the balance between these two rate-limiting factors and achieving the highest activity for CO2 reduction.

20.
Int J Health Plann Manage ; 34(4): e1800-e1809, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429111

RESUMO

BACKGROUND: As an important means through which to promote Chinese health care reform, the family doctor policy has attracted attention from various fields. This study aimed to explore the factors influencing residents' decision to sign with family doctors, with a view to informing the changes necessary to encourage additional residents to do so, thereby enhancing the efficacy of primary health care system reform. METHODS: The residents of five communities in Xianning, Hubei Province, were selected, by convenience sampling, to participate in the study. We developed and administered a questionnaire to collect data, from which we obtained 725 valid response sets. Socio-demographic characteristics were summarized using descriptive statistics; and Pearson chi-squared test and binary logistic regression were performed to identify the factors influencing residents' decision to sign with family doctors. RESULTS: We found that the factors influencing residents' decision to sign include their education level, medical insurance, chronic diseases, medical treatment habits, awareness of the family doctor policy, perception of the medical skills of family doctors, and attitudes towards family doctors' signing services (P < .05). CONCLUSION: To encourage more residents to sign with family doctors, we recommend the implementation of the following: increasing publicity for the family doctor policy, promoting the reasonable distribution of high-quality resources, augmenting the standard of general medical education, and improving the skills and competencies of family doctors.


Assuntos
Escolha da Profissão , Reforma dos Serviços de Saúde , Internato e Residência/estatística & dados numéricos , Médicos de Família/organização & administração , Adulto , Idoso , China , Feminino , Reforma dos Serviços de Saúde/organização & administração , Reforma dos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Médicos de Família/estatística & dados numéricos , Atenção Primária à Saúde/organização & administração , Atenção Primária à Saúde/estatística & dados numéricos , Inquéritos e Questionários
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