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1.
Artigo em Inglês | MEDLINE | ID: mdl-33411171

RESUMO

To measure the seroprevalence of high-exposure populations in brucellosis endemic areas and report the outcome and duration of seropositive asymptomatic subjects, we screened 595 family members of shepherds in Jilin Province, China and then followed up 15 seropositive asymptomatic subjects for 18 months. We found that the seropositive rate of 15.5%. Nearly half of seropositive asymptomatic subjects (7/15) developed into brucellosis in the short term; others were still seropositive asymptomatic or had decreased SAT titer in a longer time.

2.
J Am Chem Soc ; 143(3): 1296-1300, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33433203

RESUMO

Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.

3.
Biomaterials ; 265: 120403, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32980806

RESUMO

Local drug delivery systems, especially hydrogels, show superior strengths in postoperative recurrence prevention. Despite great advances, clinical translation of the hydrogels has been largely restricted as these drug delivery systems generally require chemical modification or additional carrier molecules to form hydrogels, which results in side effects correlative with local inflammation and systemic toxicity. Here, we developed a pure molecular anticancer drug hydrogel that reduced post-surgical tumor recurrence. The macroscopic pure molecular hydrogel was generated via ultrasonication of anticancer drug raltitrexed in aqueous solution, which was facile and environmentally friendly without involving chemical synthesis. Molecular dynamics simulations confirmed that raltitrexed self-assembled into a nanofibrous hydrogel through hydrogen bond and π-π interaction. Delivered as a hydrogel, raltitrexed could effectively decrease tumor recurrence rate and promote the inhibition of tumor growth in vivo. This raltitrexed self-delivery hydrogel has the potential to serve as a powerful auxiliary implement for preventing postoperative local tumor recurrence.

4.
Aging (Albany NY) ; 122020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33281118

RESUMO

As a pentacyclic triterpene in Centella asiatica, asiatic acid (AA) is a powerful antioxidant with many bioactivities. In the present research, we investigated whether AA has the potential to rescue the decrease in porcine oocyte quality that occurs during in vitro aging (IVA). Mature porcine oocytes were collected and then continuously cultured for an additional 24 h or 48 h with or without AA in maturation medium as an IVA model. The results revealed that AA supplementation reduced the percentage of abnormal aged porcine oocytes during IVA. Furthermore, AA supplementation effectively maintained aged porcine oocyte developmental competence, both parthenogenetic activation and in vitro fertilization. The number of sperm that bound to the zona pellucida on aged porcine oocytes was higher in the AA-supplemented group than in the non-supplemented group. Moreover, AA supplementation not only blocked IVA-induced oxidative stress but also maintained intracellular GSH levels and reduced the percentage of early apoptosis aged porcine oocytes. Mitochondrial functions were disordered during the IVA process. The intracellular ATP levels and mitochondrial membrane potential in aged porcine oocytes were dramatically increased by AA supplementation. Therefore, AA has beneficial effects on porcine oocyte quality and developmental potential maintenance during IVA.

5.
Chemosphere ; 265: 129153, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33302207

RESUMO

The abuse of antibiotics has brought out serious bacterial resistance, which threatens the ecological environment and human health. Quorum sensing inhibitors (QSIs), as a new kind of potential antibiotic substitutes that are theoretically difficult to trigger bacterial resistance, are recommended to individually use or jointly use with traditional antibiotics. However, there are few studies on the resistance risk in the use of QSIs. In this study, the influence of QSIs alone or in combination with sulfonamides (SAs) on conjugative transfer and mutation of Escherichia coli (E. coli) was investigated to explore whether QSIs have the potential to induce bacterial resistance. The results show that QSIs may facilitate plasmid RP4 conjugative transfer by binding with SdiA protein to regulate pilus expression, and interact with LsrR protein to increase SOS gene expression, inducing gene mutation. The QSIs-SAs mixtures could promote plasmid RP4 conjugative transfer and mutation in E. coli, and the main joint effects are synergism and antagonism. Furthermore, there is a good correlation among conjugative transfer, mutation, and growth inhibition of QSIs-SAs to E. coli. It could be speculated that bacteria may delay cell division to provide sufficient energy and time for regulating conjugative transfer and mutation under the stress of QSIs and their combined exposure with antibiotics, which is essentially a balance between bacterial resistance and toxicity. This study provides a reference for the resistance risk assessment of QSIs and benefits the clinical application of QSIs.

6.
Ann Palliat Med ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33353350

RESUMO

BACKGROUND: Therapeutic options for patients with second lung tumor (SLT) after previous pneumonectomy for lung cancer are sparsely reported and controversial. This study aims to compare the short- and long-term outcomes of different treatment patterns in patient with resectable postpneumonectomy SLT. METHODS: Patients received previous pneumonectomy and subsequently occurred resectable SLT were extracted from the Surveillance, Epidemiology, and End Results (SEER) database [1998-2016]. Treatment related mortality was compared using the Pearson chi-square test. Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). RESULTS: Ninety-nine patients met the selection criteria with 5-year CSS and OS rates of 60.8% and 53.7%, respectively: 23 patients received no lung resection (nLR) and 76 patients received lung resection (LR). There was no statistically significant difference between nLR group and LR group in both treatment related mortality (0.0% vs. 2.6%, P=0.432), CSS (58.3% vs. 61.7%, P=0.633) and OS (55.3% vs. 53.3%, P=0.635). Patients with subsequent adenocarcinoma (P=0.001) and smaller tumor size of SLT (P<0.001) were more likely to receive LR treatment. In the LR subgroup analysis, patients received sublobar resection (SLR) had better CSS [hazard ratio (HR): 0.381, 95% confidence interval (CI): 0.176-0.827, P=0.030] and OS (HR: 0.562, 95% CI: 0.287-1.100, P=0.051) than those received lobectomy. CONCLUSIONS: SLR or non-surgical resection is reasonable therapeutic option for patients with resectable SLT after previous pneumonectomy to achieve long-term survival, with acceptable treatment related mortality.

7.
Clin Lung Cancer ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33187913

RESUMO

BACKGROUND: Lobectomy with systematic lymph node dissection (SND) remains the standard procedure for resectable non-small-cell lung cancer (NSCLC), whereas lobe-specific lymph node dissection (LSND) was reported to have more advantages in perioperative recovery and complication reduction in treating early-stage diseases. Survival outcomes after LSND remains controversial compared with SND. PATIENTS AND METHODS: From 2014 to 2017, data of 546 patients with clinical stage IA solid-dominant NSCLC and who underwent curative lobectomies with LSND (n = 100) or SND (n = 446) at our institution were collected. Propensity score matching was conducted to eliminate the biases. Five-year disease-free survival and overall survival were compared between the groups. Perioperative parameters and postoperative complications were also analyzed. RESULTS: Lobectomies with LSND or SND were performed in 100 patients and 446 patients, respectively. After matching, there were 100 patients in each group and no significant differences in 5-year overall survival (P = .473) and disease-free survival (P = .789) were found between the groups. Recurrence patterns were also similar (P = .733). Perioperative parameters were similar, whereas the incidence of postoperative complications in the SND group was found to be significantly higher than that in the LSND group (P = .003). CONCLUSIONS: Our study demonstrated that LSND has similar efficiency to SND in terms of survival, recurrence, lymph node dissection, and perioperative recovery of patients with clinical stage IA solid-dominant NSCLC, as well as significant advantages in reducing postoperative complications. Therefore, curative lobectomies with LSND may be more suitable and practical for clinical stage IA solid-dominant patients with NSCLC.

8.
J Neurooncol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128099

RESUMO

PURPOSE: Long noncoding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed lncRNA RP11-84E24.3 regulates the pathogenesis of glioma is not fully understood. Here, we investigate the function of lncRNA RP11-84E24.3 in glioma onset and progression as well as identify a molecular pathway regulated by this lncRNA. METHODS: Differentially expressed lncRNAs related to glioma were identified. The aberrant expression of lncRNA RP11-84E24.3 was verified in samples from patients with glioma as well as glioma cell lines. The role of lncRNA RP11-8424.3 in proliferation, apoptosis, migration, and invasion was assessed using gain- and loss-of function approaches, EdU incorporation, flow cytometry, wound healing and Transwell invasion assays. Western blot analysis was utilized to examine the expression of proteins associated with epithelial-to-mesenchymal transition (EMT). The interaction between lncRNA RP11-84E24.3, TFAP2C and SNAI1 was confirmed using RNA pull-down, ChIP and luciferase reporter assays. RESULTS: LncRNA RP11-84E24.3 was up-regulated in both glioma tissues and cell lines. LncRNA RP11-84E24.3 overexpression enhanced the proliferation, migration and invasion of glioma cells while reducing apoptosis. This was associated with a decrease in E-cadherin expression and an increase in N-cadherin and Vimentin expression. LncRNA RP11-84E24.3 directly targeted TFAP2C protein, resulting in increased SNAI1 expression. Knockdown of TFAP2C or SNAI1 reversed the effects of lncRNA RP11-84E24.3 overexpression, while silencing lncRNA RP11-84E24.3 inhibited tumor formation of glioma cells in vivo. CONCLUSIONS: LncRNA RP11-84E24.3 increased SNAI1 expression by forming a complex with TFAP2C protein, promoting EMT in glioma cells and tumor formation.

9.
Front Microbiol ; 11: 506068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013774

RESUMO

Acinetobacter baumannii (A. baumannii) has emerged as one of the most troublesome pathogens in health care institutions. A. baumannii can cause a wide range of diseases in humans, including pneumonia and septicemia. Phage therapy has drawn great interest from medical researchers as a potential way to control infections by antibiotic-resistant A. baumannii. Using a pandrug-resistant clinical A. baumannii isolate ABZY9 as an indicator, we isolated a lytic phage Abp9 from hospital sewage. Abp9 belongs to myoviridae family and shows a wider host range of 12%. Abp9 contains a linear double-stranded DNA genome of 44,820 bp with a G + C content of 37.69%. The Abp9 genome contains 80 open reading frames, but lacks any known virulence genes or lysogen-formation genes. In a systemic A. baumannii infection mouse models, Abp9 treatment showed good therapeutic effects. We have also observed an excellent lytic activity against A. baumannii in biofilm form of growth in vitro. All of these suggest that Abp9 is a good candidate for the phage therapy against drug-resistant A. baumannii infections.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33043628

RESUMO

Anterolateral thigh (ALT) free flaps are widely used for reconstruction, but poor sensory recovery of the flap tissue can cause unsatisfactory outcomes and poor function. Adipose-derived mesenchymal stem cells (ADSCs) promote neural regeneration, but the clinical use of stem-cell therapy has been limited by lack of regulatory approval. Nanofat is an autologous product that is prepared mechanically from harvested fat. It is enriched in ADSCs and does not contain any exogenous substances. The developmental and adult neurobiology of nerve-growth factor (NGF) are well investigated, and mouse (m)NGF has been used to promote recovery following peripheral nerve injury. We investigated the promotion of nanofat and mNGF as either mono- or combined therapy on the sensory recovery of ALT free flaps. We found that nanofat and mNGF had a synergistic effect on sensory recovery that was associated with stimulation of angiogenesis and neurogenesis. Nanofat combined with mNGF was better at promoting neural regeneration and improving sensory recovery than treatment with either agent alone. The results provide a theoretical rationale for further study of the clinical use of nanofat combined with mNGF to promote the sensory recovery of ALT free flaps.

11.
ACS Appl Mater Interfaces ; 12(41): 45830-45837, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32936615

RESUMO

Herein, we report a novel strategy to enhance the antisense activity and the pharmacokinetics of therapeutic oligonucleotides. Through the DNA hybridization chain reaction, DNA hairpins modified with poly(ethylene glycol) (PEG) form a bottlebrush architecture consisting of a double-stranded DNA backbone, PEG side chains, and antisense overhangs. The assembled structure exhibits high PEG density on the surface, which suppresses unwanted interactions between the DNA and proteins (e.g., enzymatic degradation) while allowing the antisense overhangs to hybridize with the mRNA target and thereby deplete target protein expression. We show that these PEGylated bottlebrushes targeting oncogenic KRAS can achieve much higher antisense efficacy compared with unassembled hairpins with or without PEGylation and can inhibit the proliferation of lung cancer cells bearing the G12C mutant KRAS gene. Meanwhile, these structures exhibit elevated blood retention times in vivo due to the biological stealth properties of PEG and the high molecular weight of the overall assembly. Collectively, this self-assembly approach bears the characteristics of a simple, safe, yet highly translatable strategy to improve the biopharmaceutical properties of therapeutic oligonucleotides.

12.
Transbound Emerg Dis ; 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32696554

RESUMO

Brucellosis is a natural epidemic zoonotic disease. Liaoning province, north-east of China, has been among the top 10 provinces with highest brucellosis incidence. In this study, the spatial and temporal distribution of brucellosis in Liaoning Province from 2006 through 2017 was analysed using the Bayesian theory of space-time modelling. The study found that in Liaoning Province, (a) all regions of the entire study area were stable counties; (b) the risk of brucellosis declined slowly with time without an obvious trend; (c) the declining trend of disease risk in three sub-hot-spot counties was faster than the overall trend, whereas in other counties, the trend was similar to the overall trend. Furthermore, the time and spatial trends of brucellosis incidence in Liaoning Province were calculated and analysed. These results may provide a theoretical and scientific basis for the public health department to develop targeted effective prevention and control measures for the disease.

13.
Chemosphere ; 261: 127669, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32721686

RESUMO

Hormesis, a biphasic dose-response relationship characterized by low-dose stimulation and high-dose inhibition, has been reported to be closely related to energy sources in cultivation systems. However, few studies have clarified how the energy source influences hormesis. In this study, based on the typical diauxic patterns of Escherichia coli (E. coli) growth in mixed cultivation media containing 1.0 g L-1 glucose and Luria-Bertani broth, the hormetic response of sulfonamides (SAs) to E. coli growth was investigated under this diauxic growth condition to thoroughly explain the close relationship between hormesis and energy sources in cultivation systems. The results indicated that SAs trigger time-dependent hormetic effects on E. coli growth over the span of 24 h, in which the biphasic dose-response occurs only during the second lag and the earlier stage of the second log phase of diauxic growth. Mechanistic exploration reveals that SAs can bind with adenylate cyclase at a low dose and dihydropteroate synthase at a high dose, respectively, activating the stimulatory and inhibitory signaling pathway to influence carbon catabolite repression in diauxic growth, which can interfere with the metabolism of tryptone and yeast extract to ultimately trigger hormesis. Moreover, the stimulatory and inhibitory effects of SAs are changed by the variations in metabolic status at different growth phases, resulting in time-dependent hormesis. This study proposes an induced mechanistic explanation of hormesis in mixed cultivation media based on the energy source's metabolism, which may not only reflect the generalizability of hormesis but also further promote its application in production activities.


Assuntos
Hormese/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Escherichia coli , Sulfonamidas/farmacologia
14.
J Thorac Dis ; 12(5): 2137-2145, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32642118

RESUMO

Background: Non-small cell lung cancer (NSCLC) is one of the cancers with the highest morbidity and mortality among the world. Studies have shown that the invasion and metastasis of tumor are biological characteristics of lung cancer, and also the main cause of treatment failure and patient death. In-depth study of lung cancer invasion related genes will help to explore the etiology of lung cancer, molecular typing and individualized treatment of lung cancer. Studies have shown that CD276 molecules are closely related to the prognosis of tumors, but the exact mechanism remains to be unclear. Methods: We used the UALCAN and KM-plotter databases to investigate the expression of CD276 in human NSCLC and adjacent normal tissues, and its correlation with clinicopathology. In addition, we analyzed the function of CD276 in NSCLC cell by suppressing the expression of CD276 in A549 and H460 cells. Results: In this study, we found that CD276 expression was significantly up-regulated in NSCLC tissues, and its expression was positively correlated with tumor stage in NSCLC. Silencing in CD276 inhibited cell invasion and migration by reducing integrin-associated protein expression. Conclusions: Our results indicate functional role of CD276 in the progression of NSCLC.

15.
J Thorac Dis ; 12(5): 2583-2594, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32642166

RESUMO

Background: The aim of this population-based study was to perform competing risk analysis and estimate cancer- and other cause-specific mortality in patients who underwent oesophagectomy with pT1N0M0 oesophageal cancer (EC). A competing risks nomogram was also developed to predict the proportional of death from each specific cause. Methods: A total of 1,144 patients who received oesophagectomy for pT1N0M0 EC between 2010 and 2015 from SEER database were included. The cumulative incidence function was used to evaluate each cause of death, and the significant difference was assessed by the Grey's test. A nomogram was established using the proportional subdistribution hazard analysis to identify predictors for each cause-specific death. Results: The 5-year cumulative incidence of cancer-specific death for surgically resected pT1N0M0 EC was 15.7%, and the incidence was 11.2% for other cause-specific death. Age, tumour length, pT1 substage, grade, history and primary site were identified as predictive factors for EC-specific death, but only age, tumor length and pT1 substage were associated with death from other cause. Our nomograms showed a relative good discriminative ability, with c-index of 0.663 for the EC-specific mortality model and 0.699 for the other cause-specific mortality model. The calibration curves showed a good match between the nomogram-predicted probabilities and the actual probabilities. Conclusions: In patients who underwent curative-intent resection for pT1N0M0 EC, death from other causes was an important competing event. During clinical decision making and patient-clinician communication, our quantifiable nomograms could provide a rapid and precise judgement of the risk of death from each cause.

16.
Stem Cells Int ; 2020: 9054514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612663

RESUMO

Adipose-derived stem cell- (ADSC-) based regenerative medicine has expanded to include the treatment of hair loss. However, stem cell therapy remains a relatively recent technique, and reports of its use for treating alopecia are rare. ADSCs exert biological functions via the paracrine actions of various growth factors and cytokines. Conditioned medium from ADSCs (ADSCs-CM) is a cell-free suspension rich in growth factors and cytokines that has demonstrated a significant role in stimulating hair growth, with encouraging outcomes in terms of hair regeneration and hair growth. Extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) is an ADSC- and adipose native extracellular matrix-enriched product for cytotherapy. In this study, we compared the effects of CM from ECM/SVF-gel (ECM/SVF-CM) and from stem cells (SVF-CM) on hair growth in mice. ECM/SVF-CM stimulated hair growth more than SVF-CM, through promoting the proliferation of dermal papilla cells and cells in the bulge, neovascularization, and anagen induction. ECM/SVF-CM might, thus, provide an effective and improved strategy for promoting hair growth. These data provide a theoretical foundation for the clinical administration of ECM/SVF-CM for the treatment of hair loss.

17.
Environ Sci Technol ; 54(10): 6235-6243, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32352757

RESUMO

Gut microbiota of wildlife are usually exposed to and involved in degrading environmental pollutants, yet their biodegrading capacity remains largely unexplored. Here, we analyzed gut microbial profiles of a marine benthic polychaete, Nereis succinea, and elaborated the capacity of gut microbiota in degrading various organic pollutants, including polycyclic aromatic hydrocarbons, pesticides, phenols, and synthetic musks. High-throughput sequencing analysis revealed that the structures of microbial communities, including bacteria, fungi, and archaea, varied along the gut, manifesting distinct structural features in the fore-, mid-, and hindgut regions. Community-level physiological profiles and the capacity of gut microbiota in degrading the pollutants showed profound gut region and oxygen dependent features. In general, anaerobes were more active in degrading the pollutants, and those in the midgut presented the maximum degrading potential. Degradation capability of the gut microbiota was further quantitatively validated in an in vitro culture system using chlorpyrifos and malathion as representative compounds. Our results demonstrated a potential impact of gut microbiota in wildlife on the fate of organic pollutants in the ecosystem, which calls for further research on the influences of gut microbiota on biotransformation and bioaccumulation of xenobiotics in organisms.


Assuntos
Poluentes Ambientais , Microbioma Gastrointestinal , Microbiota , Poliquetos , Hidrocarbonetos Policíclicos Aromáticos , Animais
18.
J Am Chem Soc ; 142(23): 10297-10301, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32453555

RESUMO

Herein, we report the DNA-mediated self-assembly of bivalent bottlebrush polymers, a process akin to the step-growth polymerization of small molecule monomers. In these "condensation reactions", the polymer serves as a steric guide to limit DNA hybridization in a fixed direction, while the DNA serves as a functional group equivalent, connecting complementary brushes to form well-defined, one-dimensional nanostructures. The polymerization was studied using spectroscopy, microscopy, and scattering techniques and was modeled numerically. The model made predictions of the degree of polymerization and size distribution of the assembled products, and suggested the potential for branching at hybridization junctions, all of which were confirmed experimentally. This study serves as a theoretical basis for the polymer-assembly approach which has the potential to open up new possibilities for suprapolymers with controlled architecture, macromonomer sequence, and end-group functionalities.

19.
Eur J Surg Oncol ; 46(10 Pt A): 1888-1895, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32418755

RESUMO

OBJECTIVE: Tracheobronchial mucoepidermoid carcinoma (TMEC) is an extremely rare salivary gland-type neoplasm. We aimed to explore the clinical characteristics and prognosis of TMEC and to compare them with those of another rare salivary gland-type neoplasm, tracheobronchial adenoid cystic carcinoma (TACC). METHOD: We performed a retrospective review of all patients pathologically diagnosed with TMEC between 1965 and 2017 at our institution. We reviewed the patients' clinical characteristics, treatment methods and outcomes and compared the results of TMEC and TACC patients. RESULTS: A total of 115 consecutive patients, including 107 who underwent surgery and 8 who received nonoperative therapy, were included in our study. The 1-, 2-, and 5-year survival rates were 97.89%, 94.17%, and 90.50%, respectively, in the surgical group and 83.33%, 41.67% and 0.00%, respectively, in the nonoperative group. The multivariate analysis showed that N stage was an independent prognostic factor for overall survival (OS). TMEC patients were younger, had a shorter complaint duration, had fewer symptoms, had more bronchial tumors, and were more likely to undergo surgical treatment and achieve an R0 resection (surgically treated patients) than TACC patients; furthermore, TMEC patients had a significantly better OS than TACC patients (P < 0.050). CONCLUSIONS: TMEC has different characteristics and a better prognosis than TACC, which may reflect the different biological behaviors of these two salivary gland neoplasms. Radical treatment and close follow-up are critical for surgically treated TMEC patients with lymph node metastasis.

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