Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.721
Filtrar
1.
IEEE Trans Vis Comput Graph ; 26(1): 343-352, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31443019

RESUMO

Think-aloud protocols are widely used by user experience (UX) practitioners in usability testing to uncover issues in user interface design. It is often arduous to analyze large amounts of recorded think-aloud sessions and few UX practitioners have an opportunity to get a second perspective during their analysis due to time and resource constraints. Inspired by the recent research that shows subtle verbalization and speech patterns tend to occur when users encounter usability problems, we take the first step to design and evaluate an intelligent visual analytics tool that leverages such patterns to identify usability problem encounters and present them to UX practitioners to assist their analysis. We first conducted and recorded think-aloud sessions, and then extracted textual and acoustic features from the recordings and trained machine learning (ML) models to detect problem encounters. Next, we iteratively designed and developed a visual analytics tool, VisTA, which enables dynamic investigation of think-aloud sessions with a timeline visualization of ML predictions and input features. We conducted a between-subjects laboratory study to compare three conditions, i.e., VisTA, VisTASimple (no visualization of the ML's input features), and Baseline (no ML information at all), with 30 UX professionals. The findings show that UX professionals identified more problem encounters when using VisTA than Baseline by leveraging the problem visualization as an overview, anticipations, and anchors as well as the feature visualization as a means to understand what ML considers and omits. Our findings also provide insights into how they treated ML, dealt with (dis)agreement with ML, and reviewed the videos (i.e., play, pause, and rewind).

2.
J Hazard Mater ; 383: 121224, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31546214

RESUMO

Toxicities of microplastics (MPs) on aquatic organisms have been widely investigated often by using white or transparent MPs. However, various colored MPs scatter in the real aquatic environment. Here we investigated four colored MPs' effects on Scenedesmus obliquus algal growth first. Under the light condition, algal growth increased initially due to hormesis stimulation and then decreased gradually at higher MP concentrations. Green colored MPs exhibited the lowest inhibition effect, probably due to their resemblance to algae; white MPs inhibited the algal growth significantly, which was attributed to the presence of ethanol. Turbulence condition seemed to diminish algal growth differences among groups, but it led to slight oxidative stress. Furthermore, we also tested MP effects on Daphnia magna feeding ability. Results indicated that daphnids were probably not able to distinguish colored MPs from algae. But their algae ingestion amounts increased when MPs reached to 40% of algal cells, probably because daphnids could widen their filtering gapes when food quality decreases. However, this phenomenon did not last until the 3rd day, as the agglomeration of MPs and algae made them settle down. Overall, our results highlighted the color may alter some MP effects and is necessary to be considered in (eco)toxicological studies.

3.
Cancer Res Treat ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671936

RESUMO

Purpose: To investigate the prognostic impact of EBV-miR-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. Materials and Methods: Quantitative reverse transcription-PCR (qRT-PCR) and western blotting (WB) were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. Results: p53 aberration was associated with higher expression level of Epstein-Barr virus (EBV)-microRNA (miRNA, miR)-BHRF1-1 (p<0.001) which was also an independent prognostic marker for overall survival (OS) (p=0.028; HR 5.335 [1.193, 23.846]) in 97 newly-diagnosed CLL patients after adjusted with CLL-international prognostic index (CLL-IPI). We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3' untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. Conclusion: This study supported a role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31672275

RESUMO

Previous studies showed that miR-124 had a protective role by reducing oxidant stress and preventing cell apoptosis and autophagy. However, its role in doxorubicin-induced cardiomyopathy was less known. In our study, we confirmed increased ROS and decreased expression of miR-124 in doxorubicin-treated heart tissues and primary cardiomyocytes. The oxidative stress and cell apoptosis were alleviated by overexpressing miR-124, characterized by decreased activity of MDA and increased activity of SOD. While inhibiting miR-124 generated opposed effects. Mechanistically, our bioinformatic prediction and luciferase assay confirmed that miR-124 inhibited the expression of p66Shc, a proapoptotic signaling pathway. Our results suggested that miR-124 was hopeful to become a therapeutic target in doxorubicin-related cardiomyopathy.

5.
Int J Infect Dis ; 90: 151-160, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672657

RESUMO

BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China.

6.
Stem Cell Res ; 41: 101611, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31707209

RESUMO

We established an induced pluripotent stem cell (iPSC) line (SDQLCHi010-A) from peripheral blood mononuclear cells isolated from a 4-year-old boy with optic nerve malformation and intellectual disability carrying a heterozygous mutation (c.220A>G (p.S74G)) in PAX6 gene. Non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC were used for reprogramming. The established iPSC line showed normal karyotype, expressed pluripotency markers, exhibited differentiation potential in vitro and kept PAX6 gene mutation.

7.
Stem Cell Res ; 41: 101635, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31707215

RESUMO

Autism spectrum disorder (ASD) is a childhood-onset neurodevelopmental disorder challenged in social reciprocity and restrictive repetitive behaviors. Here, we generated an induced pluripotent stem cell (iPSC) line SDQLCHi014-A from a patient with ASD and hyperactivity, carrying a 303 kb de novo deletion at chr3p26.1 implicating GRM7 gene by reprogramming urine cells with non-integrating vectors. SDQLCHi014-A have shown full pluripotency, differentiation capacity and genetic stability. This iPSC line provides a valuable resource to study the molecular mechanisms underlying ASD.

8.
Mol Ther Nucleic Acids ; 18: 954-965, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31770672

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is due to the excessive lipid accumulation within hepatocytes. Metabolic nuclear receptors (MNRs) play great roles in lipid homeostasis. We have identified a novel long noncoding RNA (lncRNA), lnc-HC, which regulates hepatocytic cholesterol metabolism through reducing Cyp7a1 and Abca1 expression. Here, we further elucidate its roles in hepatic fatty acid and triglyceride (TG) metabolism through a novel lncRNA regulatory mechanism. The most prominent target of lnc-HC identified by in vitro study is PPARγ. Further studies revealed that lnc-HC negatively regulates PPARγ at both the mRNA and protein levels and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPARγ expression depends on modulating miR-130b-3p expression from the transcriptional to the post-transcriptional level, not through lncRNA's critical modulating patterns. In vivo, the reduction of lnc-HC expression significantly decreases miR-130b-3p expression, induces PPARγ expression, and increases TG concentration in rat livers with hyperlipidemia. These findings further help in understanding the regulatory pattern of lnc-HC in hepatic lipid metabolism and might present a possible therapeutic target for improving lipid homeostasis.

9.
Food Chem ; : 125897, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31771914

RESUMO

Paraquat (PQ) poisoning is a serious threat to human health that leads to pulmonary toxicity, neurotoxicity, and inflammation. Protecting humans from PQ exposure requires the development of rapid analytical methods for on-site detection. Here, two monoclonal antibodies against PQ were generated and an immunochromatographic assay (ICA) was exploited to determine PQ concentrations in water samples. The results showed that the monoclonal antibody 1D6 exhibited higher affinity and sensitivity, with an affinity constant of 5.4 × 108 mol/L and a limit of detection as low as 0.02 ng/mL. Without sample pretreatment, the developed ICA method provided visible limits of detection ranging from 0.25 to 1 ng/mL, and cut-off limits ranging from 1 to 5 ng/mL, where average recoveries were between 83.15% ± 1.9% and 94.49% ± 2.45% with a coefficient of variation ranging from 1.40% to 7.37%. Importantly, these observations were consistent with liquid chromatography tandem mass spectrometry. These data and results suggested that the ICA method was a reliable, portable, and high-throughput method for determining PQ residues in water samples.

10.
Oxid Med Cell Longev ; 2019: 7902874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772709

RESUMO

Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.

11.
Mucosal Immunol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776431

RESUMO

Parasitic helminths cause significant damage as they migrate through host tissues to complete their life cycle. While chronic helminth infections are characterized by a well-described Type 2 immune response, the early, tissue-invasive stages are not well understood. Here we investigate the immune pathways activated during the early stages of Heligmosomoides polygyrus bakeri (Hpb), a natural parasitic roundworm of mice. In contrast to the Type 2 immune response present at later stages of infection, a robust Type 1 immune signature including IFNg production was dominant at the time of parasite invasion and granuloma formation. This early response was associated with an accumulation of activated Natural Killer (NK) cells, with no increase of other innate lymphoid cell populations. Parabiosis and confocal microscopy studies indicated that NK cells were recruited from circulation to the small intestine, where they surrounded parasitic larvae. NK cell recruitment required IFNγ receptor signaling, but was independent of CXCR3 expression. The depletion of tissue-infiltrating NK cells altered neither worm burden nor parasite fitness, but increased vascular injury, suggesting a role for NK cells in mediating tissue protection. Together, these data identify an unexpected role for NK cells in promoting disease tolerance during the invasive stage of an enteric helminth infection.

12.
Acta Pharmacol Sin ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776449

RESUMO

Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized ß = 0.185, P < 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816-0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31776907

RESUMO

In view of the increasing attention on antibiotic contamination and their scarce data in the inland river (especially for the sediment), the occurrence of 28 antibiotics in sediments from the Xiangjiang River was comprehensively analyzed, and 22 antibiotics were detected with a total concentration ranging from 4.07 to 2090 ng g-1. The residue was almost at a moderate or higher level in the aquatic environment around the world. Fluoroquinolones and tetracyclines were the dominant detected antibiotics, and the maximum total concentration could reach to 2085 ng g-1, though that in surface water was just 33.4 ng L-1. Oxytetracycline and chlortetracycline could be detected with high concentration in areas with lower population density. Usage profile of each antibiotic may be responsible for the spatial variation. Principal component analysis-multiple linear regression model indicated that direct discharge of domestic wastewater and livestock or aquaculture sewage could contribute 94.2% of the pollution. Redundancy analysis was used to screen out the environment variables, which were closely related to the pseudo-partitioning coefficients (Kd) of antibiotics in sediment and surface water for the first time, and showed that the Kd was correlated with sediment pH negatively and organic carbon, total phosphorus, and conductivity of the sediments positively. High sedimentary organic carbon was considered to promote the higher Kd in this river. This study would deepen the understanding of the occurrence of antibiotics in sediments from the inland rivers and provide scientific support for controlling the antibiotic contamination.

14.
J Endocrinol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770098

RESUMO

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance, metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism are not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed a decreased blood glucose and serum insulin, and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the additional of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway. Which may offer novel opportunities for treatment of obesity and diabetes.

15.
ACS Synth Biol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774653

RESUMO

The 4-O-ß-D-glucopyranoside of DMEP ((-)-4-desmethylepipodophyllotoxin) (GDMEP), a natural product from Podophyllum hexandrum, is the direct precursor to the topoisomerase inhibitor etoposide, used in dozens of chemotherapy regimens for various malignancies. The biosynthesis pathway for DMEP has been completed, while the enzyme for biosynthesizing GDMEP is still unclear. Here, we report the enzymatic O-glycosylation of DMEP with 53% conversion by exploring the substrate promiscuity and entrances of glycosyltransferases. Notably, we found 6 essential amino acid residues surrounding the putative substrate entrances exposed to the protein surface in UGT78D2, CsUGT78D2 and CsUGT78D2-like, and these residues may determine substrate specificity and high O-glycosylation activity towards DMEP. Our results provide an effective route for one-step synthesis of GDMEP. Identification of the key residues and entrances of glycosyltransferases will promote precise identification of glycosyltransferase biocatalysts for novel substrates and provide a rational basis for glycosyltransferase engineering.

16.
Stem Cell Res ; 41: 101585, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31775088

RESUMO

The human induced pluripotent stem cell (iPSC) line SDQLCHi013-A was generated from peripheral blood mononuclear cells of a 7-day-old infant, who was diagnosed with maple syrup urine disease and carried compound heterozygote mutations (c.1280_1282 delTGG and c.632C>T) in BCKDHA gene. Non-integrating episomal vectors coding OCT4, SOX2, KLF4, BCL-XL and MYC were used for reprogramming. The established iPSC line contained the same mutations found in the patient, possessed a normal karyotype, could differentiate into cells of three germ layers in vitro and expressed pluripotency markers.

17.
Neuropeptides ; : 101996, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31776011

RESUMO

Stress-induced hyperalgesia is a problematic condition that lacks an effective therapeutic measure, and hence impairs health-related quality of life. The regulation of stress by oxytocin (OT) has overlapping effects on pain. OT can alleviate pain directly mainly at the spinal level and the peripheral tissues. Additionally, OT plays an analgesic role by dealing with stress and fear learning. When OT relieves stress by targeting the prefrontal brain regions and the hypothalamic-pituitary-adrenal axis, the body's sensitivity to pain is attenuated. Meanwhile, OT facilitates fear learning and may, in turn, enhance the anticipatory actions to painful stimulation. The unique therapeutic value of OT in patients suffering from stress and stress-related hyperalgesia conditions is worth considering. We reviewed recent advances in animal and human studies involving the effects of OT on stress and pain, and discussed the possible targets of OT within the descending and ascending pathways in the central nervous system. This review provides an overview of the evidence on the role of OT in alleviating stress-induced hyperalgesia.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31740121

RESUMO

This study describes the preparation of a novel multilayer sensor based on molecularly imprinted polymers (MIPs) for the detection of trace-level chlorophenols by surface-enhanced Raman scattering (SERS). Composites of SiO2/reduced graphene oxide/gold (SiO2/rGO/Au, SGA) are chosen as the SERS substrates. The fabricated composites are able to enhance the SERS sensitivity, and the addition of MIPs improves the selectivity of traditional SERS substrates. Furthermore, the sensor's detection sensitivity and selectivity are improved by including two functional monomers, namely methacrylic acid (MAA) and acrylamide (AM) containing different functional groups. Finally, in to more effectively balance the selectivity of MIPs shell and the sensitivity of SERS detection, the prepared substrates are surface-modified with polydopamine (pDA) and prepared by atom transfer radical polymerization (ATRP). It is confirmed that the prepared SGA-MIPs exhibits relatively good sensitivity and selectivity in the detection of chlorophenols. Importantly, all the investigations are conducted in environmentally friendly aqueous solution, which enables scaling-up without causing pollution.

19.
Emerg Infect Dis ; 25(12): 2205-2214, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742507

RESUMO

According to the government of China, reported cases of pertussis have increased remarkably and are still increasing. To determine the genetic relatedness of Bordetella pertussis strains, we compared multilocus variable-number tandem-repeat analysis (MLVA) results for isolates from China with those from Western countries. Among 335 isolates from China, the most common virulence-associated genotype was ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3A/tcfA2, which was more frequent among isolates from northern than southern China. Isolates of this genotype were highly resistant to erythromycin. We identified 36 ptxP3 strains mainly harboring ptxA1 and prn2 (35/36); ptxP3 strains were sensitive to erythromycin and were less frequently from northern China. For all isolates, the sulfamethoxazole/trimethoprim MIC was low, indicating that this drug should be recommended for patients infected with erythromycin-resistant B. pertussis. MLVA of 150 clinical isolates identified 13 MLVA types, including 3 predominant types. Our results show that isolates circulating in China differ from those in Western countries.

20.
Int J Neurosci ; : 1-13, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31744348

RESUMO

Background and Purpose-Hyperhomocysteinemia (Hhcy) is a risk factor for stroke. Several studies have demonstrated that Hhcy was more closely linked to small vessel occlusive disease and white matter hyperintensities (WMH) in general and elderly population. Studies on WMH and homocysteine in elderly subjects are rare, and the results were inconsistent. Our study aimed to investigate the relationship between the serum homocysteine (HCY) and the severity of WMH in elderly lacunar stroke patients.Methods-Consecutive elderly (≥60 years old) lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to periventricular WMH (PVWMH) and deep WMH (DWMH) Fazekas scores. Patients with a Fazekas score (PVWMH or DWMH) of 0, 1, 2 were in mild-moderate group and 3 were in severe group. Vascular risk factors and clinical features were compared between these two groups. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors.Results-A total of 587 participants aged 60-95 years were enrolled. Patients with severe PVWMH (n = 178) had higher age (P = 0.030) and higher incidence of stroke history (P<0.001) than those in mild-moderate group. The level of serum HCY was significantly higher in patients with severe PVWMH (P=0.002). Patients with severe DWMH (n = 142) had higher age (P<0.001) and often had a history of stroke (P<0.001). The level of HCY was higher in patients with severe degree of DWMH, but had no significance (P=0.153). Multivariable logistic regression analyses showed Hhcy were independently associated with severe PVWMH after adjusted for age and vascular risk factors (P=0.014).Conclusions-Hhcy was independently associated with severe PVWMH of elderly lacunar stroke patients, but not DWMH.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA