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1.
Front Immunol ; 13: 888661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928821

RESUMO

The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases.

2.
Front Immunol ; 13: 811007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222387

RESUMO

Given the complexity and highly heterogeneous nature of the microenvironment and its effects on antitumor immunity and cancer immune evasion, the prognostic value of a single immune marker is limited. Here, we show how the integration of immune checkpoint molecule expression and tumor-associated immune cell distribution patterns can influence prognosis prediction in non-small-cell lung cancer (NSCLC) patients. We analyzed tissue microarray (TMA) data derived from multiplex immunohistochemistry results and measured the densities of tumor-infiltrating CD8+ and FOXP3+ immune cells and tumor cells (PanCK+), as well as the densities of programmed cell death 1 (PD-1)+ and programmed cell death ligand 1 (PD-L1)+ cells in the peritumor and intratumor subregions. We found a higher density of infiltrating CD8+ and FOXP3+ immune cells in the peritumoral compartment than in the intratumoral compartment. In addition, unsupervised hierarchical clustering analysis of these markers revealed that the combination of high CD8/FOXP3 expression, low PD-1 and PD-L1 immune checkpoint expression, and lack of epidermal growth factor receptor (EGFR) mutation could be a favorable predictive marker. On the other hand, based on the clustering analysis, low CD8/FOXP3 and immune checkpoint (PD-1 and PD-L1) expression might be a marker for patients who are likely to respond to strategies targeting regulatory T (Treg) cells. Furthermore, an immune risk score model was established based on multivariate Cox regression, and the risk score was determined to be an independent prognostic factor for NSCLC patients. These results indicate that the immune context is heterogeneous because of the complex interactions of different components and that using multiple factors in combination might be promising for predicting the prognosis of and stratifying NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/patologia , Contagem de Células , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral
3.
Front Genet ; 12: 769699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880906

RESUMO

To investigate refractory hypercholesterolemia, a female patient and relatives were subjected to whole-genome sequencing. The proband was found to have compound heterozygous substitutions p. Arg446Gln and c.1118+3G>T in ABCG5, one of two genes causing sitosterolemia. When tracing these variants in the full pedigree, all maternally related heterozygotes for the intronic ABCG5 variant exhibited large platelets (over 30 fl), which segregated in an autosomal dominant manner, consistent with macrothrombocytopenia, or large platelet syndrome which may be associated with a bleeding tendency. In vitro cell-line and in vivo rat model experiments supported a pathogenic role for the variant and the macrothrombocytopenia was recapitulated in heterozygous rats and human cell lines exhibiting that single variant. Ezetimibe treatment successfully ameliorated all the symptoms of the proband with sitosterolemia and resolved the macrothrombocytopenia of the treated heterozygote relatives. Subsequently, in follow up these observations, platelet size, and size distribution were measured in 1,180 individuals; 30 were found to be clinically abnormal, three of which carried a single known pathogenic ABCG5 variant (p.Arg446Ter) and two individuals carried novel ABCG5 variants of uncertain significance. In this study, we discovered that identification of large platelets and therefore a possible macrothrombocytopenia diagnosis could easily be inadvertently missed in clinical practice due to variable instrument settings. These findings suggest that ABCG5 heterozygosity may cause macrothrombocytopenia, that Ezetimibe treatment may resolve macrothrombocytopenia in such individuals, and that increased attention to platelet size on complete blood counts can aid in the identification of candidates for ABCG5 genetic testing who might benefit from Ezetimibe treatment.

4.
Front Cell Dev Biol ; 9: 673295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124056

RESUMO

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2's correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.

5.
Heliyon ; 6(9): e04533, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32944662

RESUMO

In this article, a novel method to synthesize graphene quantum dots was developed via thermal treatment of crude graphite oxide (GO) in a dry and alkaline condition to cut the crude GO sheets into small graphene quantum dots (named as aGQDs). The aGQDs are nano-scale reduced graphene oxide pieces with the sizes around 5-10 nm. The aGQDs could disperse in water for their richment of oxygen-containing groups. The fluorescence properties were carefully investigated. The aGQDS aqueous solution shows a bright yellow-green fluorescence under the UV illumination. Besides, the uranyl ions show a strong fluorescence quenching effect on the a aGQD aqueous solution even at a low concentration (~10-7 M) compared with other common ions in natural water-body, which makes that these aGQDs could be applied as a chemosensor for detection of uranyl ions with good sensitivity and selectivity.

6.
Phys Chem Chem Phys ; 22(41): 23482-23490, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-32820299

RESUMO

The p-aminothiophenol (PATP) coupling reaction on plasmon substrates such as Ag and Au nanoparticles has received extensive attention since the catalytic effect of the surface plasmon was found. Currently, in situ kinetic studies of this reaction are rare, especially those focusing on the specific role of the hot electron-hole carriers. Here, in situ electrochemical surface-enhanced Raman spectroscopy (SERS) is developed to study the plasmon catalytic reaction of PATP in a controlled aqueous environment involving the factors of O2, electron and hole carriers, and solution pH. Ag nanoparticles supported on graphite serve as a SERS substrate, which could separate hot electron-hole pairs effectively and is beneficial to study the effects of hot carriers on plasmon-driven reactions. In situ electrochemical SERS measurements reveal two reaction paths for the PATP coupling reaction. One is that plasmon-induced hot holes activate the dehydrogenation of PATP and then the radical coupling reaction to form p,p'-dimercaptoazobenzene (DMAB) under O2-free conditions. Another is likely to be that the surface Ag2O/AgOH, which is generated from Ag and 1O2/O2-, catalyzes the oxidation of PATP and then the coupling process under O2-rich conditions. Benefitting from the potential/atmosphere controlled measurements in situ, the intermediate species of PATP(NH)/PATP(N) are observed with vibrational bands at around 1056, 1202, 1253, 1395, 1514 and 1540 cm-1.

7.
ACS Appl Mater Interfaces ; 12(34): 38106-38112, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32799447

RESUMO

Platinum-based single-atom catalysts (SACs) are among the most promising candidates for the practical applications of electrochemical hydrogen evolution reaction (HER), but their catalytic efficiency remains to be further enhanced. Herein, a well-designed nanoarray-structured nitrogen-doped graphite foil (NNGF) substrate is introduced to support Pt SACs in Pt-N4 construction (Pt1/NNGF) for HER. Within NNGF, the constructed nanoarray-structured surficial layer for supporting Pt SACs could enhance the exposure of active sites to the electrolyte and improve the reaction and diffusion kinetics; meanwhile, the retained graphite structures in bulk NNGF provide not only the required electrical conductivity but also the mechanical stability and flexibility. Because of such double-layer structures of NNGF, stable Pt-N4 construction, and binder-free advantages, the Pt1/NNGF electrode exhibits a low overpotential of 0.023 V at 10 mA cm-2 and a small Tafel slope of 29.1 mV dec-1 as well as an excellent long-term durability.

8.
Hypertens Res ; 43(6): 518-524, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31925339

RESUMO

This study evaluated the impact of ventricular rate (VR) in atrial fibrillation (AF) patients with oscillometric BP measurements. This study included 138 patients with AF and 112 patients with sinus rhythm (SR) who underwent coronary angiography. Left arm BP was measured three times with an oscillometric device, and the average was recorded as the final oscillometric value. At the same time, the average of three intra-aortic BP readings was used as invasive values. Delta BP was the difference between intra-aortic and oscillometric BP. Meanwhile, the BP percentage difference (PD-BP) was calculated with the following formula: PD-BP = (delta BP/intra-aortic BP) × 100%. Based on the VR, four subgroups of AF and SR patients, <80, 80-99, 100-120, and >120 bpm, were created, and the mean PD-BP for both systolic blood pressure (SBP) and diastolic blood pressure (DBP) was significantly higher in the AF group than in the SR group. Moreover, the mean PD-SBP values gradually increased as VR increased in both groups. More importantly, the difference in PD-SBP between the AF and SR groups increased as VR increased: when VR was <80 bpm, the levels were similar (-2.0 ± 3.5 vs. -1.4 ± 2.7 mm Hg, NS), but these values in AF patients were significantly higher when VR was 80-99 bpm (-3.7 ± 5.0 vs. -1.8 ± 2.3 mm Hg, p < 0.05), 100-120 bpm (-6.1 ± 4.3 vs. -2.3 ± 1.9 mm Hg, p < 0.05) and >120 bpm (-7.8 ± 4.9 vs. -2.9 ± 1.7 mm Hg, p < 0.05). The accuracy of oscillometric BP measurements are dependent on the ventricular rate in AF patients even after three measurements, and a higher ventricular rate may result in larger underestimations of oscillometric BP.


Assuntos
Fibrilação Atrial/fisiopatologia , Determinação da Pressão Arterial/instrumentação , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Oscilometria , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
9.
Naunyn Schmiedebergs Arch Pharmacol ; 393(11): 2165-2176, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31980857

RESUMO

Hypertension is one of the risk factors for coronary heart disease. The present study investigated the mechanism of contractile dysfunction induced by serotonin (5-HT) in coronary artery in spontaneously hypertensive rats (SHRs). Coronary arteries were isolated form SHRs and Wistar rats. Arterial ring contraction was measured using a multi myograph system. Intracellular calcium concentration was measured with a Ca2+ probe fluo-4/AM in vascular smooth muscle cells (VSMCs) isolated from coronary arteries. Signaling pathway-related proteins were assayed by western blotting. A 5-HT2A receptor blocker, sarpogrelate, completely eliminated coronary artery contraction induced by 5-HT. PLCß inhibitor U73122 also significantly inhibited the response to 5-HT. Compared with the Wistar rats, serotonin (5-HT)- and CaCl2-induced coronary vasoconstriction in the SHRs was significantly reduced. Rho-associated protein kinase inhibitor Y27632, PKC inhibitor rottlerin, and L-type calcium channel blocker nifedipine inhibited the 5-HT-induced coronary artery contraction in a dose-dependent manner in SHRs and Wistar rats. However, the inhibitory effects were reduced in SHRs. In addition, store-operated Ca2+ (SOC) induced an obvious Ca2+ influx in coronary arterial smooth muscle cells, whereas SOC-mediated contraction was very slight in coronary arteries. At the same time, it was found that 5-HT2AR, IP3R, and Cav1.2 protein expression and PKCδ activity were decreased, and STIM1 and Orai1 were increased in VSMCs from coronary arteries of SHRs compared with Wistar rats. These results implicate calcium-handling dysfunction mediated by the 5-HT2A receptor and downstream signaling pathway might lead to a reduction in 5-HT-induced contraction in SHR coronary arteries.


Assuntos
Hipertensão/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Cálcio/metabolismo , Sinalização do Cálcio , Células Cultivadas , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Ratos Endogâmicos SHR , Ratos Wistar , Receptor 5-HT2A de Serotonina/metabolismo
10.
Front Pharmacol ; 11: 592116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33519452

RESUMO

Background and Aims: Aspirin leads to substantial benefits for the secondary prevention of cardiovascular disease (CVD). We aimed to cast more light on aspirin's role for the primary prevention of CVD. Methods: Databases were searched for clinical trials comparing aspirin vs. no aspirin use in this meta-analysis. Efficacy and safety profiles were rigorously investigated. Trial sequential analysis (TSA) was used to determine the robustness of the results. Results: Fourteen studies with 163,840 participants were eligible (mean follow-up 6.2 y). Aspirin intake was found to be associated with 9, 13, and 12% reductions in the risk of cardiovascular events (CV events) (relative risk [RR]: 0.91, 95% confidence intervals [CI]: 0.87-0.96; risk difference (RD): 0.29%; absolute risk percentage (AR%): 7.61%; number needed to treat (NNT): 345), myocardial infarction (RR: 0.87, 95% CI: 0.77-0.97; RD: 0.21%; AR%: 11.11%; NNT: 488) and ischemic stroke (RR: 0.88, 95% CI: 0.80-0.96; RD: 0.21%; AR%: 16.14%; NNT: 476), respectively; aspirin intake was also associated with 40%, 30%, and 57% increases in the risk of major bleeding (RR: 1.40, 95% CI: 1.29-1.53; RD: 0.47%; AR%: 27.85; NNT: 214), intracranial bleeding (RR: 1.30, 95% CI: 1.11-1.52; RD: 0.10%; AR%: 22.99%; NNT: 1,000) and major gastrointestinal bleeding (RR: 1.57, 95% CI: 1.38-1.78; RD: 0.32%; AR%: 36.70%; NNT: 315), respectively. Further, populations with low doses of aspirin intake (≤100 mg), populations <65 y old or populations with body mass index (BMI) ≧ 25 experienced more advantages; high-risk (10-y cardiovascular risk ≧10%) and full diabetic individuals reported hardly clinical benefits. Conclusion: Aspirin intake was associated with a reduced risk of CV events and an increased incidence of bleeding profiles in primary prevention. It is necessary to identify individual's CVD risk using clear examinations or assessments before aspirin intake, and truly realize individualized prescription.

11.
Inorg Chem ; 58(19): 13066-13076, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31556292

RESUMO

Cerium oxides are prevalent catalytic materials, and the lanthanide-doped ceria have attracted special interest since it is easy to tune the concentration of oxygen vacancies (VO) by changing the doping content. The presence of VO is generally believed to favor a catalytic reaction, but the formation of dopant-vacancy associations at a high doping concentration might produce an adverse effect. Herein, evolutions of the structural properties and catalytic performances in Sm-doped ceria (SmxCe1-xO2-δ, x = 0-1) are investigated to explore the doping effect of Sm3+ on the ceria-based nanoctrystals. The SmxCe1-xO2-δ films composed of nanoctrystals are elaborately prepared via electrodeposition under mild conditions to prevent phase separation. A combination of studies, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman, photoluminescence (PL), and methanol electro-oxidation (MEO) reaction, reveals that variation trends for the VO concentration and catalytic property of SmxCe1-xO2-δ are unsynchronized. The lattice structures of SmxCe1-xO2-δ nanoctrystals undergo a smooth and steady transition from F-type (fluorite CeO2) to C-type (cubic Sm2O3) with the increase of Sm3+ contents. The structural transition occurs in the Sm3+ concentration range of 64-84%, within which the VO concentration reaches the maximum as well. However, the optimal MEO performance is obtained at a relatively lower doping concentration of 24%. Above this concentration, significant dopant-vacancy associates are observed by XRD, Raman, and PL characterizations. It is inferred that, for these ceria-based nanocrystals, the dopant-vacancy association induced by high doping would impede the growth of catalytic performance despite all the benefits of VO.

12.
Front Neurol ; 10: 852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447767

RESUMO

Background: The effect of magnesium on stroke has been consistently discussed less, and the results of previous studies have been contradictory. We reviewed the latest literature and quantified robust evidence of the association between magnesium intake and stroke risk. Methods: PubMed, EMBASE, the Cochrane Library, the Web of Science and ClinicalTrials.gov were searched through inception to January 15, 2019 for prospective cohort studies on magnesium intake and the incidence of stroke. Results: Fifteen studies with low bias involving 18 cohorts were entered into this study. The summary relative risk (RR) was significantly reduced by 11% for total stroke (RR: 0.89 [95% CI, 0.83-0.94]; P < 0.001) and by 12% for ischemic stroke (RR: 0.88 [95% CI, 0.81-0.95]; P = 0.001), comparing the highest magnesium intake category to the lowest. After adjusting for calcium intake, the inverse association still existed for total stroke (RR: 0.89 ([95% CI, 0.80-0.99]; P = 0.040). There was an inverse but non-significant association for hemorrhagic stroke, subarachnoid hemorrhage and intracerebral hemorrhage. The quantitative associations for total and ischemic stroke were robust. Importantly, high-risk females who had a body mass index (BMI) ≥25 kg/m2 and who were subjected to a ≥12 y follow-up exhibited a greater decrease in RRs as a result of magnesium intake. For each 100 mg/day increase in magnesium, the risk for total stroke was reduced by 2% and the risk for ischemic stroke was reduced by 2%. Conclusions: Increasing magnesium intake may be a crucial component of stroke prevention that acts in a dose-dependent manner. However, the conclusion is limited by the observational nature of the studies examined, and further randomized controlled trials are still needed.

13.
ChemistryOpen ; 8(7): 1027-1032, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31367510

RESUMO

Developing cost-effective and highly efficient oxygen evolution reaction (OER) electrocatalysts is vital for the production of clean hydrogen by electrocatalytic water splitting. Here, three dimensional nickel-iron layered double hydroxide (NiFe LDH) nanosheet arrays are in-situ fabricated on self-supporting nitrogen doped graphited foam (NGF) via a one-step hydrothermal process under an optimized amount of urea. The as prepared NiFe LDH/NGF electrode exhibits a remarkable activity toward OER with a low onset overpotential of 233 mV and a Tafel slope of 59.4 mV dec-1 as well as a long-term durability. Such good performance is attributed to the synergy among the doping effect, the binder-free characteristic, and the architecture of the nanosheet array.

14.
Mikrochim Acta ; 186(9): 603, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385118

RESUMO

A flexible adhesive tape decorated with SERS-active silver nanorods (AgNRs) in the form of an array nanostructure is described. The tape was constructed by transferring the AgNRs nanostructures from silicon to the transparent tape by a "paste & peel off" procedure. The transparent, sticky, and flexible properties of commercial tapes allow almost any SERS-inactive irregular surface to be detected in-situ by pasting the SERS tape onto the position to be analyzed. Three examples for an analytical application are presented, viz. determination of (a) tetramethylthiuram disulfide and thiabendazole (two pesticides), (b) colorants in the gel of a writing pen, and (c) the fluorophore Rhodamine B. The tetramethylthiuram disulfide on apple surface was rapidly detected with a LOD of 28.8 ng·cm-2. The AgNRs effectively quenched the fluorescence of the matrix and fluorophores, this enabling the colorants and Rhodamine B to be identified. The results demonstrated that the SERS tape can be used for versatile in-situ detection. Conceivably, it may find applications in food analysis, non-invasive identification, environmental monitoring, and in other areas of daily life. Graphic abstract A flexible and adhesive SERS active tape decorated with silver nanorods (AgNRs) arrays was constructed through a "paste & peel off" method. It can be used as a versatile in situ analysis platform for various applications.

15.
ACS Omega ; 4(7): 12319-12324, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31460349

RESUMO

Surface-enhanced Raman spectroscopy (SERS) has been utilized for rapid analysis of uranyl ions (UO2 2+) on account of its fast response and high sensitivity. However, the difficulty of fabricating a suitable SERS substrate for in situ analysis of uranyl ions severely restricts its practical application. Hence, we proposed flexible and adhesive SERS tape decorated with silver nanorod (AgNR) arrays for in situ detection of UO2 2+. The SERS tape was fabricated through a simple "paste & peel off" procedure by transferring the slanted AgNR arrays from silicon to the transparent tape surface. UO2 2+ can be easily in situ detected by placing the AgNR SERS tape into an aqueous solution or pasting it onto the solid matrix surface due to the excellent transparent feature of the tape. The proposed SERS tape with well-distributed AgNRs effectively improved the reproducibility and sensitivity for UO2 2+ analysis. UO2 2+ with concentration as low as 100 nM was easily detected. Besides, UO2 2+ adsorbed on an iron disc and rock surface also can be rapidly in situ detected. With its simplicity and convenience, the AgNR SERS tape-based SERS technique offers a promising approach for environmental monitoring and nuclear accident emergency detection.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30296235

RESUMO

Sufficient training data normally is required to train deeply learned models. However, due to the expensive manual process for labelling large number of images (i.e., annotation), the amount of available training data (i.e., real data) is always limited. To produce more data for training a deep network, Generative Adversarial Network (GAN) can be used to generate artificial sample data (i.e., generated data). However, the generated data usually does not have annotation labels. To solve this problem, in this paper, we propose a virtual label called Multi-pseudo Regularized Label (MpRL) and assign it to the generated data. With MpRL, the generated data will be used as the supplementary of real training data to train a deep neural network in a semi-supervised learning fashion. To build the corresponding relationship between the real data and generated data, MpRL assigns each generated data a proper virtual label which reflects the likelihood of the affiliation of the generated data to predefined training classes in the real data domain. Unlike the traditional label which usually is a single integral number, the virtual label proposed in this work is a set of weight-based values each individual of which is a number in (0,1] called multi-pseudo label and reflects the degree of relation between each generated data to every pre-defined class of real data. A comprehensive evaluation is carried out by adopting two state-of-the-art convolutional neural networks (CNNs) in our experiments to verify the effectiveness of MpRL. Experiments demonstrate that by assigning MpRL to generated data, we can further improve the person re-ID performance on five re-ID datasets, i.e., Market-1501, DukeMTMC-reID, CUHK03, VIPeR, and CUHK01. The proposed method obtains +6.29%, +6.30%, +5.58%, +5.84%, and +3.48% improvements in rank-1 accuracy over a strong CNN baseline on the five datasets respectively, and outperforms state-of-the-art methods.

17.
Am J Cardiol ; 122(4): 592-596, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29958713

RESUMO

Long-term heart rate (HR) control is a management strategy for patients with chronic atrial fibrillation (AF). Nevertheless, the optimal target HR of AF patients is debatable. Our aim was to study HR at rest, during, and after a 6-minute walk test (6MWT) in AF patients, compared with controls with sinus rhythm (SR). Consecutive matched patients with AF (n = 186) or SR (n = 172) were recruited, and 6MWT was performed. HRs at rest, during 6MWT, and recovery periods were recorded. All subjects were divided into 5 subgroups (<80 beats/min, 80 to 89 beats/min, 90 to 99 beats/min, 100 to 109 beats/min, and ≥110 beats/min) according to the HR at rest. No statistical difference was observed in baseline HR at rest, between AF and SR groups (p = 0.30). The exercise HR increase percentage was significantly higher in overall AF patients compared with those in SR (40 ± 15% vs 14 ± 7%, p <0.001). Even with similar mean baseline HRs at rest, the 5 AF subgroups all showed significantly higher mean exercise HR, maximal exercise HR, and maximal exercise HR increase percentage compared with their respective SR subgroups, especially the subgroups with HR at rest >90 beats/min. Unlike the SR patients, the 4 AF subgroups with HR >80 beats/min at the fifth minute after 6MWT did not recover to at rest levels. In conclusion, HR increased excessively during 6MWT and HR recovery was delayed after 6MWT in AF patients, especially when HR at rest is >90 beats/min. The optimal initial HR at rest for AF patients should perhaps be <90 beats/min.


Assuntos
Fibrilação Atrial/fisiopatologia , Função Atrial/fisiologia , Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Recuperação de Função Fisiológica/fisiologia , Teste de Caminhada/métodos , Fibrilação Atrial/diagnóstico , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Biochem Pharmacol ; 154: 183-192, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29746822

RESUMO

Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly isolated from Catharanthus roseus, and a potential drug candidate for treatment of cancer and Alzheimer's disease (AD), however, its anti-inflammatory effect has not been revealed. In this study, we reported that tabersonine ameliorated lipopolysaccharides (LPS)-induced ALI in vivo and inhibited LPS-mediated macrophage activation in vitro. By using murine ALI model, we found that tabersonine significantly attenuated LPS-induced pathological injury in the lung. Tabersonine also inhibited LPS-mediated neutrophil infiltration, elevation of MPO activity and the production of TNF-α, IL-6 and IL-1ß. Furthermore, tabersonine inhibited LPS-induced the production of pro-inflammatory mediators such as iNOS, NO and cytokines by suppressing NF-κB and p38 MAPK/MK2 signaling cascades. Tabersonine reduced the K63-linked polyubiquitination of TRAF6. Taken together, these results suggested that tabersonine has anti-inflammatory activities in vitro and in vivo, and is a potential therapeutic candidate for the treatment of ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Alcaloides Indólicos/uso terapêutico , Lipopolissacarídeos/toxicidade , Quinolinas/uso terapêutico , Fator 6 Associado a Receptor de TNF/antagonistas & inibidores , Ubiquitinação/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Relação Dose-Resposta a Droga , Alcaloides Indólicos/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinolinas/farmacologia , Distribuição Aleatória , Fator 6 Associado a Receptor de TNF/metabolismo , Ubiquitinação/fisiologia
19.
Dev Cell ; 38(5): 453-62, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27569419

RESUMO

Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to formyl peptide receptor 1 (FPR1) and subsequent FPR1 internalization and signaling inhibition. The oxidant sensing-induced termination of neutrophil migration at the site of infection permits a smooth transition to the subsequent microbial killing phase.


Assuntos
Inflamação/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores de Formil Peptídeo/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Movimento Celular/genética , Células HL-60 , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/enzimologia , Camundongos , Neutrófilos/metabolismo , Oxidantes/metabolismo , Peroxidase/metabolismo , Receptores de Formil Peptídeo/genética , Canais de Cátion TRPM/genética
20.
Am J Emerg Med ; 33(8): 1072-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25983270

RESUMO

SUBJECT: The aim of this study was to compare the predictive values of modified shock index (MSI) and shock index (SI) for 7-day outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This retrospective study included 160 consecutive patients with STEMI and emergency percutaneous coronary intervention. The blood pressure (BP) and heart rate (HR) measured at emergency department were used to calculate SI (HR/systolic BP) and MSI (HR/mean artery pressure). The major adverse cardiac events (MACE) included all-cause mortality, life-threatening arrhythmias, cardiogenic shock, and Killip class within 7 days. RESULTS: Forty-nine patients had increased MSI (≥1.4), whereas 72 had increased SI (≥0.7). Except the parameters on BP and HR, other parameters were similar between the normal and increased SI groups. However, the increased MSI group had significantly higher age (69.0 ± 13.0 years vs 63.9 ± 12.9 years, P = .025) than the normal MSI group. The 7-day all-cause mortality was 8.8%, and MACE rate was 24.4% in this study. Both increased SI and increased MSI predicted higher MACE rates. However, the odds ratios of increased MSI for all-cause mortality (6.8 vs 3.4), cardiogenic shock (3.0 vs 1.6), life-threatening arrhythmias (9.1 vs 4.6), and MACE (6.8 vs 3.4) were higher than those of increased SI. Modified shock index and SI were independent factor for MACE, but the odds ratio of MSI was higher than of SI (3.05 vs 1.07). CONCLUSIONS: Both SI and MSI in emergency department could predict the all-cause mortality and MACE rates within 7 days in patients with STEMI, but MSI may be more accurate than SI.


Assuntos
Arritmias Cardíacas/mortalidade , Pressão Arterial/fisiologia , Frequência Cardíaca/fisiologia , Infarto do Miocárdio/mortalidade , Choque Cardiogênico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Pressão Sanguínea/fisiologia , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/fisiopatologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Choque Cardiogênico/etiologia , Choque Cardiogênico/fisiopatologia
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