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1.
J Hazard Mater ; 382: 121041, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470295

RESUMO

The high concentration of chloride (Cl-) ions in leachate often has negative effects in their harmless treatments, and the common treatments containing the ion exchange method consume excessive antichlors due to their large particle sizes and unfavorable morphologies. Herein, the antichlors of the Bi(III) containing oxides with quantum dots (QDs) or two-dimensional (2D) structures are first explored for the removal and recovery of Cl- ions in concentrated leachate. By using the QDs/2D flakes constructed antichlors of Bi2O3 and the magnetite Bi-Ti composite, the maximum Cl- removal rates of 61.8% and 66.1% are respectively achieved under the optimum conditions. The higher removal efficiency of the magnetite Bi-Ti composite is contributed by its less stable crystal phases of Bi25FeO40/Bi12TiO20, which can proceed more deeply in the removal of Cl- ions compared with that of Bi2O3. The recovered terminal magnetite Bi-Ti precipitate with Bi2O3/BiOCl heterostructure exhibits excellent photocatalytic activity in the degradation of the dechlorinated leachate, where a total organic carbon removal rate of 87.2% is achieved under UV-vis-near-infrared irradiation. Therefore, the selection of Bi(III) containing oxides opens a promising and high-value method for the removal and recovery of Cl- ions in leachate and other waste waters.

2.
Talanta ; 207: 120293, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594564

RESUMO

Droplet digital PCR (ddPCR) has attracted much attention in the detection of genetic signatures of cancer present at low levels in circulating tumor DNA (ctDNA) in blood. A growing number of laboratory-developed liquid biopsy tests based on such technology have become commercially available for clinical settings. To obtain consistent and comparable results, an international standard is necessary for validation of the analytical performance. In this study, a novel and SI-traceable "ctDNA" reference material (RM) carrying BRAF V600E was prepared by gravimetrically mixing a 152 bp PCR amplicon and sonicated wild-type genomic DNA. The ddPCR performance was evaluated by analyzing serial "ctDNA" dilutions using a competitive MGB assay. The mutant frequency concordance (k) between ddPCR and the gravimetrical value was 1.03 in the range from 53.9% to 0.1%. The limit of blank (LoB), detection (LoD) and quantification (LoQ) of ddPCR assay were determined to be 0.01%, 0.02% and 0.1%, respectively. Results from the interlaboratory study, using challenging low levels of BRAF V600E ctDNA RMs, demonstrated that the participating laboratories had the appropriate technical competency to perform accurate ddPCR-based low level of ratio measurements. However, a systematic error caused by uncorrected droplet volume in Naica Crystal ddPCR platform was found by using the ctDNA RM. Between-laboratory consistency in copy number measurement was greatly improved when a correct droplet volume was applied for the ddPCR measurement by using the ctDNA RM. This confirms that the "ctDNA" RM is fit for the validation of ddPCR systems for ctDNA quantification. This would also support translation of tests for circulating tumor DNA by ddPCR into routine use.

3.
Med Decis Making ; : 272989X19890296, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795820

RESUMO

Introduction. Enhanced visual effects, like animation, have the potential to improve comprehension of probabilistic risk information, particularly for those with lower health literacy. We tested the effect of presentation format on comprehension of colorectal cancer (CRC) screening probabilities to identify optimal risk communication strategies. Methods. Participants from a community foodbank and a cancer prevention center were randomized to 1 of 3 CRC screening risk presentations. The presentations used identical content but varied in format: 1) video with animated pictographs, 2) video with static pictographs, and 3) audiobooklet with static pictographs. Participants completed pre- and postpresentation surveys. The primary outcome was knowledge of probability/risk information regarding CRC screening, calculated as total, verbatim, and gist scores. Results. In total, 187 participants completed the study and were included in this analysis. Median age was 58 years (interquartile range [IQR]: 14 years), most participants were women (63%), and almost half had a high school education or less (46%). Approximately one-quarter had inadequate health literacy (Short Test of Functional Health Literacy in Adults marginal/inadequate: 28%; Brief Health Literacy Screener low: 18%), and about half had low numeracy (Subjective Numeracy Scale low: 54%; Graphical Literacy Measure low: 50%). We found no significant differences in total, verbatim, or gist knowledge across presentation formats (all P > 0.05). Discussion. Use of an animated pictograph to communicate risk does not appear to augment or impede knowledge of risk information. Regardless of health literacy level, difficulty understanding pictographs presenting numerical information persists. There may be a benefit to teaching or priming individuals on how to interpret numerical information presented in pictographs before communicating risk using visual methods. Trial Registry: NCT02151032.

4.
J Vis Exp ; (153)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31789319

RESUMO

Elevated intraocular pressure (IOP) is a well-documented risk factor for glaucoma. Here we describe a novel, effective method for consistently inducing stable IOP elevation in mice that mimics the post-operative complication of using silicone oil (SO) as a tamponade agent in human vitreoretinal surgery. In this protocol, SO is injected into the anterior chamber of the mouse eye to block the pupil and prevent inflow of aqueous humor. The posterior chamber accumulates aqueous humor and this in turn increases the IOP of the posterior segment. A single SO injection produces reliable, sufficient, and stable IOP elevation, which induces significant glaucomatous neurodegeneration. This model is a true replicate of secondary glaucoma in the eye clinic. To further mimic the clinical setting, SO can be removed from the anterior chamber to reopen the drainage pathway and allow inflow of aqueous humor, which is drained through the trabecular meshwork (TM) at the angle of the anterior chamber. Because IOP quickly returns to normal, the model can be used to test the effect of lowering IOP on glaucomatous retinal ganglion cells. This method is straightforward, does not require special equipment or repeat procedures, closely simulates clinical situations, and may be applicable to diverse animal species. However, minor modifications may be required.

5.
Pancreatology ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31791885

RESUMO

OBJECTIVE: This exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC). METHODS: A retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis. RESULTS: A total of 179 patients' samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAP patients, of which 20 controls, 20 CP, and 58 PDAC patients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64-0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64-0.90) and 0.76 (95% CI 0.67-0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93-1.00) CONCLUSION: This study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.

6.
Cell Signal ; 66: 109483, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760170

RESUMO

BACKGROUND: Chemoresistance is one of the main obstacles in the therapy of human cancers, including colorectal cancer (CRC). Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) has been demonstrated to be associated with CRC. However, the function of HAND2-AS1 in 5-Fluorouracil (5-FU) resistance of CRC remains unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HAND2-AS1, miR-20a and programmed cell death factor 4 (PDCD4) mRNA. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was conducted to evaluate IC50 of 5-FU and cell proliferation. Flow cytometry analysis was used to determine cell apoptosis. Transwell assay was carried out to measure cell migration and invasion. Western blot assay was conducted to examine the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), matrix metalloprotein 2 (MMP2), MMP9 and PDCD4. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were utilized to verify the combination between miR-20a and HAND2-AS1. Dual-luciferase reporter assay was used to analyze the association between miR-20a and PDCD4. Murine xenograft assay was used to confirm the function of HAND2-AS1 in vivo. RESULTS: HAND2-AS1 and PDCD4 were downregulated and miR-20a was upregulated in 5-FU-resistant CRC tissues and cells. HAND2-AS1 suppressed 5-FU resistance, cell proliferation, migration and invasion and promoted cell apoptosis in 5-FU-resistant CRC cells. HAND2-AS1 acted as a sponge of miR-20a to regulate PDCD4 expression. Moreover, HAND2-AS1 suppressed cell progression and 5-FU resistance by upregulating PDCD4 via sponging miR-20a in 5-FU-resistant CRC cells. Besides, HAND2-AS1 inhibited tumor growth in vivo. CONCLUSION: HAND2-AS1/miR-20a/PDCD4 axis inhibited cell progression and 5-FU resistance in 5-FU-resistant CRC cells.

7.
Sensors (Basel) ; 19(21)2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31684132

RESUMO

Bioradar-based noncontact breathing detection technology has been widely studied due to its superior detection performance. In this paper, a breath detection mechanism based on the change in radar cross section (RCS) is proposed by using a forward scatter radar and the deduction of the mathematical model of the received signal. Furthermore, we completed human breathing detection experiments in an anechoic chamber and in an ordinary chamber; we obtained the breathing rate through envelope detection in cases where the human orientation angle was 0, 30, 60, and 90°. The analysis of the measured data shows that the theoretical model fits well with the measured results. Compared with the existing single-base radar detection schemes, the proposed scheme can detect human respiratory rates in different orientations.

8.
Cell Res ; 29(12): 1027-1034, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31729466

RESUMO

Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of the stress response. The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism. Here, we determined the cryo-EM structures of human SMG1 at 3.6 Å resolution and the SMG1-SMG8-SMG9 complex at 3.4 Å resolution, respectively. SMG8 has a C-terminal kinase inhibitory domain (KID), which covers the catalytic pocket and inhibits the kinase activity of SMG1. Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8-SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity. Thus, our structural and biochemical analyses provide a mechanistic understanding of SMG1-SMG8-SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity.

9.
Environ Int ; 134: 105283, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743806

RESUMO

In the last decade, North China (NC) has been one of the most populated and polluted regions in the world. The regional air pollution has had a serious impact on people's health; thus, all levels of government have implemented various pollution prevention measures since 2013. Based on multi-city in situ environmental and meteorological data, as well as the meteorological reanalysis dataset from 2013 to 2017, regional pollution characteristics and meteorological formation mechanisms were analyzed to provide a more comprehensive understanding of the evolution of PM2.5 in NC. The domain-averaged PM2.5 was 79 ±â€¯17 µg m-3 from 2013 to 2017, with a decreasing rate of 10 µg m-3 yr-1. Two automatic computer algorithms were established to identify 6 daily regional pollution types (DRPTs) and 48 persistent regional pollution events (PRPEs) over NC during 2014-2017. The average PM2.5 concentration for the Large-Region-Pollution type (including the Large-Moderate-Region-Pollution and Large-Severe-Region-Pollution types) was 113 ±â€¯40 µg m-3, and more than half of Large-Region-Pollution days and PRPEs occurred in winter. The PRPEs in NC mainly developed from the area south of Hebei. The number of Large-Region-Pollution days decreased notably from 2014 to 2017, the annual number of days varying between 194 and 97 days, whereas a slight decline was observed in winter. In addition, the averaged PM2.5 concentrations and the numbers and durations of the PRPEs decreased. Lamb-Jenkinson weather typing was used to reveal the impact of synoptic circulations on PM2.5 across NC. Generally, the contributions of the variations in circulation to the reduction in PM2.5 levels over NC between 2013 and 2017 were 64% and 45% in summer and winter, respectively. The three most highly polluted weather types were types C, S and E, with an average PM2.5 concentration of 137 ±â€¯40 µg m-3 in winter. Furthermore, three typical circulation dynamics were categorized in the peak stage of the PRPEs, namely, the southerly airflow pattern, the northerly airflow pattern and anticyclone pattern; the averaged relative humidity, recirculation index, wind speed and boundary layer height were 63%, 0.33, 2.0 m s-1 and 493 m, respectively. Our results imply that additional emission reduction measures should be implemented under unfavorable meteorological situations to attain ambient air quality standards in the future.

10.
Zhen Ci Yan Jiu ; 44(11): 858-9, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31777239

RESUMO

In the present paper, we introduce a newly modified device named "transcutaneous electrical auricular concha stimulator (TEACS)" for rats. It concludes a main unit (power and control buttons) with newly designed specific output electrodes. Each of the output electrode is made up of two pieces of iron sheet containing magnet and can be firmly attached to the auricular concha and the corresponding site of dorsal auricle, respectively. The two iron sheets are separately connected to each of the output terminal of the main unit via two pieces of wire. This newly modified output electrode replaces the original wire clip, and solves the problems of easy loosening and easy injury of the original spring clip due to repeated usage, being simple, flexible and convenient in application.


Assuntos
Terapia por Estimulação Elétrica , Estimulação Elétrica Nervosa Transcutânea , Animais , Ratos
11.
Oncol Rep ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746410

RESUMO

MicroRNAs (miRNAs/miRs) in exosomes play crucial roles in the onset, progression and metastasis of cancer by regulating the stability of target mRNAs or by inhibiting translation. In the present study, differentially expressed miRNAs were identified in exosomes of 27 breast cancer patients and 3 healthy controls using RNA sequencing. The differentially expressed microRNAs were selected by bioinformatic analysis. Subjects were followed up for 2 years and exosomal miRNA profiles were compared between patients with and without recurrence of breast cancer. A total of 30 complementary DNA libraries were constructed and sequenced and 1,835 miRNAs were detected. There were no significant differences in the expression of miRNAs between the basal­like, human epidermal growth factor receptor­2+, luminal A, luminal B and healthy control (HC) groups. A total of 54 differentially expressed miRNAs were identified in triple­negative breast cancer (TNBC) patients vs. HCs, including 20 upregulated and 34 downregulated miRNAs. The results of the reverse transcription­quantitative PCR were consistent with this. Receiver operating characteristic curve analyses indicated that miR­150­5p [area under the curve (AUC)=0.705, upregulated], miR­576­3p (AUC=0.691, upregulated), miR­4665­5p (AUC=0.681, upregulated) were able to distinguish breast cancer patients with recurrence from those without recurrence. In conclusion, the present results indicated differences in miRNA expression profiles between patients with TNBC and healthy controls. Certain exosomal miRNAs were indicated to have promising predictive value as biomarkers for distinguishing breast cancer with recurrence from non­recurrence, which may be utilized for preventive strategies.

12.
Int J Oncol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31746425

RESUMO

Epithelial ovarian cancer is aggressive and lacks effective prognostic indicators or therapeutic targets. In the present study, using immunohistochemistry and bioinformatics analysis on ovarian cancer tissue data from The Obstetrics and Gynecology Hospital of Fudan University and The Cancer Genome Atlas database, it was identified that FXYD domain­containing ion transport regulator 5 (FXYD5) expression was upregulated in the SKOV3­IP cell line compared with its parental cell line, SKOV3, and in ovarian cancer tissues compared with in normal tissues. In addition, FXYD5 upregulation was predictive of poor patient survival. Furthermore, through various in vitro (Transwell assay, clonogenic assay and western blot analysis) and in vivo (nude mouse model) experiments, it was demonstrated that FXYD5 promoted the metastasis of ovarian cancer cells. Mechanistically, RNA sequencing, western blot analysis, a luciferase reporter assay and chromatin immunoprecipitation were performed to reveal that FXYD5 dispersed the SMAD7­SMAD specific E3 ubiquitin protein ligase 2­TGF­ß receptor 1 (TßR1) complex, deubiquitinated and stabilized TßR1, and subsequently enhanced transforming growth factor­ß (TGF­ß) signaling and sustained TGF­ß­driven epithelial­mesenchymal transition (EMT). The TGF­ß­activated SMAD3/SMAD4 complex was in turn directly recruited to the FXYD5 promoter region, interacted with specific SMAD­binding elements, and then promoted FXYD5 transcription. In brief, FXYD5 positively regulated TGF­ß/SMADs signaling activities, which in turn induced FXYD5 expression, creating a positive feedback loop to drive EMT in the process of ovarian cancer progression. Collectively, the findings of the present study suggested a mechanism through which FXYD5 serves a critical role in the constitutive activation of the TGF­ß/SMADs signaling pathways in ovarian cancer, and provided a promising therapeutic target for human ovarian cancer.

14.
J Cell Mol Med ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733095

RESUMO

Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up-regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up-regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock-down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR-29a-3p sponge to up-regulate SLC25A15 expression by bioinformatics analysis, dual-luciferase reporter assays and biotinylated RNA pull-down assays. SLC25A15 could reverse the tumour suppressing roles of knock-down circFOXO3 in PCa. Of note, we found that miR-29a-3p was down-regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR-29a-3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up-regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

15.
Eur J Pharmacol ; : 172787, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31712061

RESUMO

Zinc finger E-box binding homeobox 1 (ZEB1) (previously known as TCF8), a transcriptional repressor, is a member of the zinc-finger family of proteins. Numerous studies have demonstrated that abnormal expression of ZEB1 in many types of liver disease including hepatocellular carcinoma (HCC). Liver fibrosis is the basis and central link in the progression of liver disease. Thereby, the function of ZEB1 in liver fibrosis has been investigated. The aim of the present study was to investigate the role of ZEB1 in liver fibrosis and to elucidate the mechanism. In this study, we explored the effect of ZEB1 in hepatic stellate cells (HSCs) activation and the regulatory mechanism of the Wnt/ß-catenin signaling pathway. Additionally, ZEB1 positively regulated the expression levels of α-SMA and Col.I in vivo and in vitro, which were correlated with the activated HSCs. Furthermore, overexpression of ZEB1 could inhibit HSCs apoptosis and promote IL-6 and TNF-α secretion in LX-2 cells. Conversely, ZEB1 silencing led to the promotion of cell proliferation and the reduction of IL-6 and TNF-α secretion in LX-2 cells. Mechanically, canonical Wnt/ß-catenin signaling pathway could be regulated by ZEB1. Collectively, the data suggested that ZEB1 might play a significant role in the activation of LX-2 cells, and Wnt/ß-catenin signaling pathway might participate in this progression.

16.
Front Immunol ; 10: 2394, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681286

RESUMO

Type III interferon-lambda (IFN-λ) plays a critical role against infection, particularly in mucosal infection in the respiratory and gastrointestinal tract. Our study and other previous studies have shown that porcine IFN-λ more efficiently curtails the infection of porcine epidemic diarrhea virus (PEDV) in the intestine epithelia than type I IFN, whereas IFN-λ3 exerts a more potent effect than IFN-λ1. However, the underlying mechanism remains elusive, and in particular, the transcriptional profile induced by IFN-λ3 has not been reported. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In contrast, IFN-α only modified the expression of 134 genes, and 110 of these genes were also observed in the response to IFN-λ3. A transcriptional enrichment analysis indicated that IFN-λ3 or IFN-α regulates multiple cellular processes and that IFN-λ3 activates more robust signaling pathways, particularly the antiviral Jak-STAT signaling pathway, than IFN-α. Furthermore, we verified the RNA-Seq results through an RT-qPCR analysis of IPEC-J2 cells and porcine enteroids. Moreover, transient expression of the porcine rsad2 and mx2 genes among the top 10 genes induced by IFN-λ3 significantly inhibited PEDV infection. Collectively, the data showed that IFN-λ3 induces a unique transcriptional profile that does not completely overlap with that induced by IFN-α and strongly elicits a set of genes responsible for the antiviral activity of IFN-λ3. These findings provide important knowledge regarding the elicited ISGs of type I and III IFNs in restricting porcine intestinal viral infection.

17.
Math Biosci Eng ; 16(6): 7659-7670, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31698632

RESUMO

Objectives: The purpose of this meta-analysis was to evaluate the efficacy and toxicity profile of apatinib for the treatment of advanced non-small cell lung cancer (NSCLC). Methods: We systematically searched databases for randomized clinical trials published as of November 25, 2017, in which apatinib treatment was compared to placebo or chemotherapy in patients with advanced NSCLC. Two investigators independently assessed the articles and extracted their data. The hazard ratios (HRs) for progression-free survival (PFS), relative risks (RRs) for overall response rates (ORRs), disease control rates (DCRs), and odds ratios (ORs) for main toxicity were analyzed using the RevMan 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Results: Our analysis included 413 patients from 5 clinical studies. The pooled HR for PFS was 0.32 (95% confidence interval (CI) 0.21-0.48; P < 0.00001). The pooled RRs for ORR and DCR were 2.03 (95% CI 1.36-3.01; P = 0.0005) and 1.66 (95% CI 1.07-2.57; P = 0.02), respectively. The pooled OR for main toxicity was 1.34 (95% CI, 0.57-3.17; P = 0.5). Conclusions: Apatinib was a viable treatment alternative for advanced NSCLC, as it offered a clinically meaningful and statistically significant improvement in PFS, ORR, and DCR. Moreover, therapy with apatinib did not significantly increase toxicity.

18.
Sensors (Basel) ; 19(22)2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31744139

RESUMO

Wireless mesh networks (WMNs) can provide flexible wireless connections in smart city, Internet of Things (IoT), and device-to-device (D2D) communications. The performance of WMNs can be greatly enhanced by adopting the multi-radio multi-channel (MR-MC) technique, which enables a node to communicate with more nodes simultaneously. However, increasing the number of data flows will result in network congestion and longer end-to-end delays. In this paper, a distributed rate-control and delay-aware (DRDA) scheduling algorithm is proposed based on a multidimensional conflict graph. To satisfy the arrival rate and delay constraints of a flow, two virtual queues are constructed. All the actual and virtual queues are stabilized by the Lyapunov drift optimization method. The scheduling policy of each flow is optimized only based on the local information. The simulation results show that our proposed algorithm can maintain the stability of all the queues and strictly satisfy the arrival rate and delay constraint of each flow in the network as well.

19.
Parasit Vectors ; 12(1): 542, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727141

RESUMO

BACKGROUND: Larvae of Echinococcus granulosus (sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced by E. granulosus (s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear. METHODS: The activation status of peritoneal macrophages (PMs) derived from mice infected with E. granulosus (sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treated in vivo and in vitro with recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected. RESULTS: The expression of AAM-related genes in PMs was preferentially induced after E. granulosus (s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated from E. granulosus (s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained after E. granulosus (s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotype in vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor. CONCLUSIONS: This study demonstrates that E. granulosus (s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part, via the PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31728800

RESUMO

PURPOSE: Protein kinase C alpha (gene: PRKCA) is a key regulator of cardiac contractility. Two genetic variants have recently been discovered to regulate PRKCA expression in failing human heart tissue (rs9909004 [T → C] and rs9303504 [C → G]). The association of those variants with clinical outcomes in patients with heart failure (HF), and their interaction with HF drug efficacy, is unknown. METHODS: Patients with HF in a prospective registry starting in 2007 were genotyped by whole genome array (n = 951). The primary outcome was all-cause mortality. Cox proportional hazards models adjusted for established clinical risk factors and genomic ancestry tested the independent association of rs9909004 or rs9303504 and the variant interactions with cornerstone HF pharmacotherapies (beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) in additive genetic models. RESULTS: The minor allele of rs9909004, but not of rs9303504, was independently associated with a decreased risk for all-cause mortality: adjusted HR = 0.81 (95% CI = 0.67-0.98), p = 0.032. The variants did not significantly interact with mortality benefit associated with cornerstone HF pharmacotherapies (p > 0.1 for all). CONCLUSIONS: A recently discovered cardiac-specific regulatory variant for PRKCA (rs9909004) was independently associated with a decreased risk for all-cause mortality in patients with HF. The variant did not interact with mortality benefit associated with cornerstone HF pharmacotherapies.

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