Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.844
Filtrar
1.
Food Chem ; 306: 125587, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31627084
2.
Waste Manag ; 101: 283-290, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648169

RESUMO

Recycling solid waste not only produces environmental and health benefits, but also generates economic benefit. This paper empirically evaluates the employment impact of Florida county recycling programs from 2000 through 2011, applying a fixed effects regression model. The results indicate that a one percentage point increase of county recycling rate leads to a 0.4% job growth in overall solid waste and recycling industry. However, the impact of recycling programs on green jobs are not uniform across the recycling subsectors: the effect is concentrated in the recycling processing sector while the solid waste collection sector and scrap materials businesses are unlikely to be influenced by county's recycling performance.


Assuntos
Gerenciamento de Resíduos , Emprego , Florida , Reciclagem , Resíduos Sólidos
3.
J Nanosci Nanotechnol ; 20(2): 949-956, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383091

RESUMO

To improve lithium storage performances of Si anode for lithium-ion batteries, Si nanoparticles encapsulated into porous N-doped carbon (Si@PNC) was devised and prepared by metal nitrate accelerated polymer blowing process. The Si@PNC composites have large specific surface area of 221.7 m² g-1 and possess a great deal of mesopores and micropores, which are attributed to the carbonization of PVP and etching metallic nanoparticles. As anode for lithium ion battery, the initial discharge capacity of Si@PNC composites is high to 1626 mA h g-1, and the specific capacity still retains 1030 mA h g-1 after 200 cycles at 200 mA g-1. Meanwhile, remarkably improved rate capability is achieved with an excellent reversible specific capacity of 375 mA h g-1 at 5.0 A g-1. The excellent lithium storage performances benefit from the unique porous core-shell structure of Si@PNC composites, which improve electroconductivity, reduce volume dilatation and accelerate lithium ion transmission.

4.
J Nanosci Nanotechnol ; 20(1): 24-30, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383136

RESUMO

Toxoplasma Gondii is an obligate intracellular protozoan. T. gondii tachyzoites can invade nucleated host cells and inhibit their apoptosis. Therefore, the goal of the present study was to determine whether rhoptry protein 16 (ROP16) secreted by the invading T. gondii can reduce the apoptotic response of the host cell. For this purpose, a vector for in vitro overexpression of T. gondii ROP16 was constructed and used to transfect human 293T cells. Cells transfected with the vector robustly expressed ROP16, as evidenced by Western blotting. Apoptosis of 293T cells was induced by incubation with 0.5 µg/mL actinomycin D (ActD) for 24 h, and its magnitude was measured using Annexin V-FITC/PI and TUNEL assays. Cells transfected by ROP16-expressing vector were characterized by a significantly lower level of apoptosis measured by both techniques.Moreover, caspase-3 activity was also reduced. Thus, ROP16 inhibited ActD-induced apoptosis of human 293T cells, documenting the ability of this rhoptry protein to modulate apoptosis of host cells infected by T. gondii.

5.
Magn Reson Imaging ; 65: 114-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629074

RESUMO

The thalamus serves as the central relay station for the brain. It processes and relays sensory and motor signals between different subcortical regions and the cerebral cortex and it can be divided into several neuronal clusters referred to as nuclei. Each of these can possibly be subdivided into sub-nuclei. Accurate and reliable identification of thalamic nuclei is important for surgical interventions and neuroanatomical studies. This is however a challenging task because the small size of the nuclei and the lack of contrast over the thalamus region in clinically acquired images does not permit the visualization of their boundaries. A number of methods have been developed for thalamus parcellation but the vast majority of these relies on diffusion imaging or functional imaging. The low resolution of these images only permit localizing the largest nuclei. In this work we propose a method to segment smaller nuclei. We first present a protocol to build histological-like atlases from a series of high-field (7 Tesla) MR images acquired with different pulse sequences that each permits to visualize the boundaries of a subset of the nuclei. We use this protocol to scan 9 subjects and we manually delineate 23 thalamic nuclei following the Morel atlas naming convention for each of these subjects. Manual contours for the nuclei are subsequently utilized to create statistical shape models. With these data, we compare four methods for the segmentation of thalamic nuclei in 3 T images we have also acquired for the 9 subjects included in the study: (1) single atlas, (2) multi atlas, (3) statistical shape, and (4) hierarchical statistical shape in which thalamic nuclei are hierarchically fitted to the images, starting from the largest ones. Results of a leave-one-out validation study conducted on the nine image sets we have acquired show that the multi atlas approach improves upon the single atlas approach for most nuclei. Segmentations obtained with the hierarchical statistical shape model yield the highest accuracy, with dice coefficients ranging from 0.53 to 0.90, mean surface errors from 0.27 mm to 0.64 mm, and maximum surface errors from 1.31 mm to 2.52 mm for all nuclei averaged across test cases. This suggests the feasibility of using such approach for localizing thalamic substructures in clinically acquired MR volumes. It may have a direct impact on surgeries such as Deep Brain Stimulation procedures that require the implantation of stimulating electrodes in specific thalamic nuclei.

6.
J Endocrinol ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794423

RESUMO

Mitochondrial quality control (MQC) and function are determinants for cellular energy metabolism and their disorders are reported to play important role in the development of insulin resistance (IR). Salidroside was reported to have beneficial effects on MQC through AMPK pathway, however, it is unknown whether salidroside exerts anti-IR effect with this action. This study sought to investigate effects of salidroside on IR with an exploration of the mechanisms of its action. Experimental IR models were adopted in high-fat diet (HFD) fed mice and palmitate-treated C2C12 myotubes, respectively. Blood levels of glucose and insulin as well as cellular glucose uptake were determined, mitochondrial function and MQC-associated parameters and reactive oxygen species (ROS) production were analyzed based on treatments with activator (AICAR), inhibitors (compound C and EX-527), or specific siRNA of AMPK/SIRT1 and mitochondrial ROS scavenger (mito-TEMPO). Protein expression level was determined by Western-Blot, cellular observation by transmission electron microscope, and ROS production by functional analysis kits. Salidroside reduced IR and activated insulin signaling along with stimulation of AMPK/SIRT1 signaling and downstream regulation of MQC and ROS production. These salidroside effects were comparable to those of AICAR and could be prevented by AMPK/SIRT1 inhibitors or siRNAs, respectively. Salidroside reduces IR and regulates MQC and ROS production through activating AMPK/SIRT1 signaling pathway. Since IR is a critical issue for public health, to explore a potent agent against IR is of high interest. The anti-IR effects of salidroside warrant further experimental and clinical studies.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31799763

RESUMO

It is a challenging but pressing task to design and synthesize novel, efficient, and robust pH-universal hydrogen evolution reaction (HER) electrocatalysts for scalable and sustainable hydrogen production through electrochemical water splitting. Here, we report a facile method to prepare an efficient and robust Ru-M (M=Ni, Mn, Cu) bimetal nanoparticle and carbon quantum dot hybrid (RuM/CQDs) for pH-universal HER. As exemplified by RuNi/CQDs, the catalysts exhibit outstanding HER performance at all pH levels. The unexpected low overpotentials of 13, 58 and 18 mV shown by RuNi/CQDs allow a current density of 10 mA cm-2 in 1 M KOH, 0.5 M H2SO4 and 1 M PBS, respectively, for Ru loading at 5.93 µgRu cm-2. This performance is among the best catalytic activities reported for any platinum-free electrocatalyst. RuMn/CQDs and RuCu/CQDs electrocatalysts also exhibit ideal performance. Theoretical calculations reveal the underlying mechanism, whereby Ni doping results in a moderate weakening of the hydrogen bonding energy of nearby surface Ru atoms, which plays a critical role in improving the HER intrinsic activity. It also improves the interconnective metal skeleton, facilitating electron transfer and leading to the superior HER performance. Thus, this study proposes a promising approach to the development of highly efficient bimetal/carbon hybrid compounds with advanced HER performance.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31787533

RESUMO

The aim of this study was to establish rapid and efficient methods based on a Tri-step infrared spectroscopy (Fourier transform infrared spectroscopy (FT-IR) integrated with second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2DCOS-IR)) and computer vision technology to identify and evaluate the quality of three Chinese dry-cured hams (Jinhua, Xuanwei and Rugao hams). 9 dry-cured hams (3 different quality grades of each geographical origin) had similar IR spectra. Nevertheless, they could be further discriminated visually by SD-IR and 2DCOS-IR spectra. All samples can be separated by the computer vision technology incorporated with Principal Component Analysis (PCA) and Cluster analysis (CA). This study not only preliminarily verified the possibility of using Tri-step infrared spectroscopy and computer vision technology to discriminate the geographical origins and quality grades of Chinese dry-cured hams, but also provided prospects of the application of infrared spectroscopy and computer vision technology to authenticate other meat products.

9.
Sci Total Environ ; : 135599, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31784146

RESUMO

Dust on air conditioning filters can represent the re-suspended particulate matter in indoor air, which may pose potential health risks to humans. However, source identification and influence factors of indoor dust are controversial. The present study investigated the distribution of Cd, Cr, Mn, Ni, Pb, Sb, V, and Zn, as well as stable carbon isotope, in indoor dust from three different functional zones in Hefei to discuss the sources and influence factors of indoor dust. PCA analysis of heavy metals showed that indoor sources (such as cooking and smoking) were the main sources. Negative correlation appeared between family size and heavy metal concentrations. This was because people acted as a sink of pollutants. Concentration analysis of heavy metals revealed that smoking and cooking had weak relevance with heavy metal concentrations. While through the δ13C analysis, cooking had a significant correlation with δ13C of indoor dust, instructing that cooking was a significant source of indoor dust. Besides, smoking also had a certain correlation with δ13C of indoor dust, instructing that smoking was one of the sources of indoor dust.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31791635

RESUMO

BACKGROUND AND AIMS: The prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM. METHODS AND RESULTS: A total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7-47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626-0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64-4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11-2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001). CONCLUSION: The PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment.

11.
Clin Exp Metastasis ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792675

RESUMO

The papillary thyroid carcinoma (PTC) usually shows an excellent prognosis. But some patients suffer recurrence after treatment. Recent progress in RNA sequencing (RNA-Seq) allows us to explore whole-transcriptomic gene expression profiles to develop RNA-seq based predictive model for stratifying the risk of recurrence of PTC. RNA-seq and clinical data from The Cancer Genome Atlas thyroid carcinoma cohort were divided chronologically into a training cohort (before 2011, n = 240) and a validation cohort (after 2011, n = 239). A risk score model was developed in training cohort using univariate Cox analysis followed by stepwise multivariate Cox analysis, and assessed in the validation cohort. Univariate and multivariate analyses identified five independent predictive genes (TOP2A, RP11-180M15.7, RP11-635N19.1, PROSER3, and TMEM139) significantly (p < 0.05) associated with recurrence-free survival of PTC. The proposed risk score model defined by these five genes was able to divide patients into high-risk and low-risk groups with significantly different recurrence risk in both training cohort [hazard ratio (HR) 6.62, 95% confidence interval (CI) 3.16-13.86] and validation cohort [HR 3.40, 95% CI1.29-8.94). Furthermore, the model is independent of clinicopathologic factors and demonstrated better predictive performance than other clinical covariates in PTC patients with no distant metastasis. Our results indicate that TOP2A, RP11-180M15.7, RP11-635N19.1, PROSER3, and TMEM139 are potential independent predictive genes for the recurrence of PTC and the proposed RNA sequencing-based model has significant predictive value and may improve recurrence risk stratification for early-stage PTC patients.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31801694

RESUMO

Target of rapamycin (TOR) is an atypical of Ser/Thr protein kinase that plays an important role in many aspects such as cell growth, reproduction, differentiation, cell cycle regulation, autophagy and apoptosis. However, little information is known about the enzyme in crustaceans. Here, a novel TOR was identified from shrimp Penaeus vannamei (PvTOR) and its biological functions were investigated in response low temperature stress. The PvTOR gene encoded a polypeptide of 2464 amino acids with an estimated molecular mass of 279.4 kD and a predicted isoelectronic point (pI) of 7.30. Phylogenetic analysis revealed that PvTOR shared high similarity with other known species. PvTOR mRNA was detected in all the tested tissues and highest transcription in muscle and hepatopancreas. PvTOR transcriptional level was up-regulated significantly at 1.5 h and 3 h, and down-regulated at 12 h and 24 h after low temperature stress. TEM and autophagy indicator system GFP-PvLC3 suggested that low temperature induced autophagy generation. ROS, Ca2+ concentration and apoptosis rate were increased significantly in TOR-knockdown shrimp after low temperature stress. The autophagy associated gene ATG8II/I, PvBeclin-1, PvATG14, apoptosis gene PvPARP, Pvcasp-3, PvBAX and Pvp53 transcripts, and casp-3/8 activity in hemocyte were increased significantly in TOR-knockdown group shrimp at 3 h after low temperature stress. Additionally, THC counts of TOR-knockdown group were significantly higher than the dsGFP group. In summary, these results suggested that PvTOR plays an important role in the adaptation mechanisms of shrimp at low temperature by regulating autophagy and apoptosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31802624

RESUMO

CONTEXT: Catholic systems control a growing share of health care in the United States. Because patients seeking contraceptives in Catholic facilities face doctrinal restrictions that may affect access to and quality of care, it is important to understand whether and how providers work within and around institutional policies regarding contraception. METHODS: In 2016-2018, in-depth interviews were conducted in Illinois with 28 key informants-including providers (obstetrician-gynecologists, other physicians, nurse-midwives) and nonclinical professionals (ethicists, administrators, chaplains)-who had experience in secular, Protestant or Catholic health care systems. Interviews addressed multiple aspects of reproductive care and hospital and system policy. A thematic content approach was used to identify themes related to participants' experiences with and perspectives on contraceptive care. RESULTS: While respondents working in secular and Protestant systems reported few limitations on contraceptive care, those working in Catholic systems reported multiple barriers. Providers who had worked in Catholic systems described variable institutional policies and enforcement practices, ranging from verbal admonishments to lease agreements prohibiting contraceptive provision in secular clinics on church-owned land. Despite these restrictions, patients' needs motivated many providers to utilize work-arounds; some providers reported having been pressured or directly instructed to document false diagnoses in patients' medical records. Interviewees described how these obstacles burdened patients, especially those with social and financial constraints, and resulted in delayed or lower quality care. CONCLUSIONS: Providers working in Catholic hospitals are limited in their ability to serve women of reproductive age. Work-arounds intended to circumvent restrictions may inadvertently stigmatize contraception and negatively affect patient care.

14.
Mol Med Rep ; 20(5): 4523-4532, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702044

RESUMO

Betatrophin [also known as lipasin, angiopoietin­like 8 (ANGPTL8), refeeding induced in fat and liver (RIFL), or hepatocellular carcinoma­associated gene TD26], a 22­kDa protein in the angiopoietin­like family, is a liver­derived hormone that promotes pancreatic ß­cell proliferation and lipid metabolism. The aim of the present study was to investigate the effect of recombinant betatrophin on ß­cell regeneration in a neonatal streptozotocin (STZ)­induced diabetic rat model. One­day­old Wistar rats were injected with STZ (100 mg/kg), followed by intraperitoneal administration of betatrophin to the STZ­injected rats for 6 days. Plasma glucose and body weight were monitored. On days 4 and 7, expression levels of pancreatic duodenal homeobox gene­1 (PDX­1), the Bax/B­cell lymphoma­2 (Bcl­2) ratio and plasma insulin were assessed, and the ß­cell proliferation rate was determined. Pancreatic islet area and number were determined at 10 weeks. It was found that betatrophin treatment alleviated STZ­induced hyperglycemia, elevated pancreatic expression levels of Bcl­2, PDX­1, plasma insulin levels and the ß­cell proliferation rate on days 4 and 7. Long­term betatrophin treatment improved glucose tolerance, associated with improved plasma insulin levels and ß­cell mass. These results suggest that early administration of betatrophin promotes ß­cell proliferation in STZ­induced diabetic neonates and prevents the development of diabetes in adults.

15.
J Arthroplasty ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31706646

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is an increasing worldwide health problem. However, about 30% of the patients are diagnosed with idiopathic ONFH, which means no underlying etiology is identified. We hypothesized that acetabular anatomical abnormalities might be related to idiopathic ONFH. METHODS: This retrospective, 1:2 matched, case-control study included 101 patients (136 hips) with idiopathic ONFH and 202 control subjects (404 hips) matched for age, gender, and body mass index who had no apparent radiographic hip pathologies. The anteroposterior pelvic X-rays of the patients and control subjects were used to measure the anatomical parameters including the center-edge angle, the sharp angle, the acetabular depth ratio (ADR), and the acetabular head index (AHI). RESULTS: We found that hips with idiopathic osteonecrosis had less acetabular coverage, lower center-edge angle (28.3° vs 32.3°, P < .001), acetabular depth ratio (298.0 vs 306.4, P = .006), and acetabular head index (82.2 vs 85.8, P < .001), and higher sharp angle (39.7° vs 38.0°, P < .001), compared with the control subjects. The incidence of acetabular dysplasia was also higher in the idiopathic ONFH group than the control group. CONCLUSION: Less acetabular coverage was found in hips with idiopathic osteonecrosis than the control subjects. Less acetabular coverage may be associated with the development of ONFH in East Asian population.

16.
Opt Express ; 27(20): A1601-A1614, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684591

RESUMO

Optical polarization characteristics and light extraction behavior of deep-ultraviolet (DUV) light-emitting diode (LED) flip-chip with full-spatial omnidirectional reflector (FSODR) have been investigated. FSODR is fabricated to be simultaneously covered on the whole flip-chip, except the sapphire surface. It is found that the FSODR greatly enhance both transverse-electric (TE) and transverse-magnetic (TM) mode light extraction at every space angle, resulting in total enhancement of 73.1% and 79.8%, respectively. Moreover, the four individual ODR structures separated from FSODR, which are covered on the surface of n-AlGaN, the interface of p-GaN/p-AlGaN, the sidewall of mesa and the sidewall of n-AlGaN/AlN, respectively, show considerably different optical polarization characteristics and extraction behaviors between each other. The achievements of FSODR cannot be obtained by any separated ODR, and all of the individual ODRs can contribute to the FSODR. Especially, the synergy effect of TM extraction behavior obviously exists in FSODR. As a result, the light extraction efficiency (LEE) enhancement of FSODR is approximately 60% at a high current density of 140A/cm2. This study is significant for understanding and modulating the extraction behavior of polarized light to realize high efficiency AlGaN-based DUV LEDs.

17.
J Hazard Mater ; : 121556, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711724

RESUMO

The widespread contamination and high poisonousness have created significant concerns and thus demands for facile, rapid and selective monitoring of trace Hg2+. Inspired from the unique aggregation-induced emission (AIE) feature, in the current study, novel tetraphenylethylene (TPE) derivatives are prepared containing sulfonic groups for water solubility modulation and carboxyl dithioacetals for Hg2+ sensing. The TPE derivatives are grafted on electrospun fiber as test papers to initiate the AIE activities, while the Hg2+-specific cleavage of dithioacetal groups leads to the release of TPE derivatives and fluorescence turn-off. The decrease in the fluorescence intensities of fibrous mats could be fitted with Hg2+ levels for quantitative analysis, and the fibrous mats turn from green to bluish-green and then to blue in the presence of different Hg2+ levels. The limit of detection (LOD) reaches as low as 20 nM Hg2+, satisfying the threshold detection in drinking water, and the Hg2+ sensing indicates negligible interference from other metal ions and pH variations. The detected Hg2+ levels in lake water are consistent with the added amount with a recovery rate of over 98 %. It demonstrates a feasible strategy to integrate Hg2+-cleavable AIE probes on fibrous strips for real-time, highly specific and naked-eye detection of trace Hg2+.

18.
Theor Appl Genet ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31720702

RESUMO

KEY MESSAGE: A total of 12 QTL conferring resistance to tan spot induced by a race 2 isolate, 86-124, were identified in three tetraploid wheat mapping populations. Durum is a tetraploid species of wheat and an important food crop. Tan spot, caused by the necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr), is a major foliar disease of both tetraploid durum wheat and hexaploid bread wheat. Understanding the Ptr-wheat interaction and identifying major QTL can facilitate the development of resistant cultivars and effectively mitigate the negative effect of this disease. Over 100 QTL have already been discovered in hexaploid bread wheat, whereas few mapping studies have been conducted in durum wheat. Utilizing resistant resources and identifying novel resistant loci in tetraploid wheat will be beneficial for the development of tan spot-resistant durum varieties. In this study, we evaluated four interconnected tetraploid wheat populations for their reactions to the race 2 isolate 86-124, which produces Ptr ToxA. Tsn1, the wheat gene that confers sensitivity to Ptr ToxA, was not associated with tan spot severity in any of the four populations. We found a total of 12 tan spot-resistant QTL among the three mapping populations. The QTL located on chromosomes 3A and 5A were detected in multiple populations and co-localized with race-nonspecific QTL identified in other mapping studies. Together, these QTL can confer high levels of resistance and can be used for the improvement in tan spot resistance in both hexaploid bread and durum wheat breeding. Two QTL on chromosomes 1B and 7A, respectively, were found in one population when inoculated with a ToxA knockout strain 86-124ΔToxA only, indicating that their association with tan spot was induced by other unidentified necrotrophic effectors, but under the absence of Ptr ToxA. In addition to removal of the known dominant susceptibility genes, integrating major race-nonspecific resistance loci like the QTL identified on chromosome 3A and 5A in this study could confer high and stable tan spot resistance in durum wheat.

19.
Nat Cell Biol ; 21(11): 1403-1412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31685984

RESUMO

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

20.
J Biomed Nanotechnol ; 15(12): 2393-2400, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748019

RESUMO

Hepatitis B virus (HBV) is closely related to occurrence and development of viral hepatitis. A mutation of 1896nt locus in its pre-C region can promote replication of HBV DNA and improve stability of pre-genome RNA structure, and can even help HBV evade immune clearance. In this study, magnetic beads-probe (MBs@probe) method, combined with single base extension (SBE) technology, was developed for in-situ mutation detection of HBV pre-C region 1896nt locus. Before successfully completing the genotyping of 165 HBV samples, the crucial reaction conditions were first optimized, such as SBE temperature, MBs size and amount, and probe concentration on the surface of MBs. Experimental results showed that these conditions had significant effects on MBs@probe in-situ mutation detection. Comprehensive considerations, such as 58 °C of SBE temperature, high fluorescence intensity and signal-to-noise ratios (SNRs) were obtained when MBs@probe complex was made by 100 µg of 300 nm-MBs and 3.0 µM of probes in the system. Finally, 1896nt locus mutation in pre-C region of 165 HBV samples was successfully genotyped, among which 71 HBV samples were wild types and the remaining 94 samples were mutant types. Meanwhile, 14 randomly chosen samples were taken to further analyze fluorescence intensity and SNRs respectively, and sequencing results for the first two samples were consistent with results from the MBs@probe in-situ mutation detection method. Compared with two-color fluorescence hybridization (TCFH) genotyping technology, this method generally improves the SNRs to more than 10 (which is more than 2-fold), has higher reliability and is more suitable to detect SNPs for known sites.


Assuntos
Vírus da Hepatite B , Herpesvirus Cercopitecino 1 , Polimorfismo de Nucleotídeo Único , DNA Viral , Genótipo , Hepatite B , Humanos , Mutação , Reprodutibilidade dos Testes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA