Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 538
Filtrar
1.
Brain Res ; : 148956, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657888

RESUMO

Recent advancements in neuroimaging have illustrated that anterior cruciate ligament (ACL) injuries could impact the central nervous system (CNS), causing neuroplastic changes in the brain beyond the traditionally understood biomechanical consequences. While most of previous functional magnetic resonance imaging (fMRI) studies have focused on localized cortical activity changes post-injury, emerging research has suggested disruptions in functional connectivity across the brain. However, these prior investigations, albeit pioneering, have been constrained by two limitations: a reliance on small-sample participant cohorts, often limited to two to three patients, potentially limiting the generalizability of findings, and an adherence to region of interest based analysis, which may overlook broader network interactions. To address these limitations, our study employed resting-state fMRI to assess whole-brain functional connectivity in 15 ACL-injured patients, comparing them to matched controls using two distinct network analysis methods. Using Network-Based Statistics, we identified widespread reductions in connectivity that spanned across multiple brain regions. Further modular connectivity analysis showed significant decreases in inter-modular connectivity between the sensorimotor and cerebellar modules, and intra-modular connectivity within the default-mode network in ACL-injured patients. Our results thus highlight a shift from localized disruptions to network-wide dysfunctions, suggesting that ACL injuries induce widespread CNS changes. This enhanced understanding has the potential to stimulate the development of strategies aiming to restore functional connectivity and improve recovery outcomes.

2.
Methods Mol Biol ; 2790: 213-226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38649573

RESUMO

Canopy photosynthesis (Ac), rather than leaf photosynthesis, is critical to gaining higher biomass production in the field because the daily or seasonal integrals of Ac correlate with the daily or seasonal integrals of biomass production. The canopy photosynthesis and transpiration measurement system (CAPTS) was developed to enable measurement of canopy photosynthetic CO2 uptake, transpiration, and respiration rates. CAPTS continuously records the CO2 concentration, water vapor concentration, air temperature, air pressure, air relative humidity, and photosynthetic photon flux density (PPFD) inside the chamber, which can be used to derive CO2 and H2O fluxes of a canopy covered by the chamber. This system can also be used to measure the fluxes of greenhouse gases when integrating with CH4 and N2O analyzers. Here, we describe the protocol for using CAPTS to perform experiments on rice (Oryza sativa L.) in paddy field, wheat (Triticum aestivum L.) in upland field, and tobacco (Nicotiana tabacum L.) in pots.

3.
J Sci Food Agric ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597282

RESUMO

BACKGROUND: Peach gum (PG) is an exudate of the peach tree (Prunus persica of the Rosaceae family), which consists primarily of polysaccharides with a large molecular weight and branching structure. Consequently, PG can only swell in water and not dissolve directly, which severely limits its application. Current conventional extraction methods for PG polysaccharide (PGPS) are time-consuming and inefficient. This study investigated the impact of ultrasonic-assisted extraction (UAE) on PGPS structure and conformation, as well as their relationship to hypoglycemic activity in vitro. RESULTS: Compared to conventional aqueous extraction, UAE enhanced PGPS yield from 28.07%-32.83% to 80.37%-84.90% (w/w) in 2 h. It drastically decreased the molecular size and conformational parameters of PGPS, including Mw, Mn, Rg, Rh and [η] values. PGPS conformation converted from extended molecules to flexible random coil chains or compact spheres with no obvious primary structure alteration. Furthermore, UAE altered the flow behaviour of PGPS solution from non-Newtonian fluid to Newtonian fluid. As a result, PGPS treated with ultrasonic displayed weaker inhibitory activity than those untreated, mostly because UAE weakens the binding strength of PGPS to α-glucosidase. However, this negative effect of UAE on PGPS activity was compensated by the increased solubility of polysaccharide. This enabled PGPS to achieve a wider range of doses. CONCLUSION: UAE is capable of degrading PGPS efficiently while preserving its primary structure, resulting in a Newtonian fluid solution. The degraded PGPS conformation display a consistent correlation with their inhibitory effect on α-glucosidase activity. This article is protected by copyright. All rights reserved.

4.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612598

RESUMO

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.


Assuntos
Doenças Mitocondriais , Pancreatite , Quercetina/análogos & derivados , Animais , Camundongos , Pancreatite/tratamento farmacológico , Doença Aguda , Simulação de Acoplamento Molecular , Mitocôndrias , Transdução de Sinais
6.
Bioorg Chem ; 146: 107286, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537336

RESUMO

Pulmonary fibrosis (PF) poses a significant challenge with limited treatment options and a high mortality rate of approximately 45 %. Qingkailing Granule (QKL), derived from the Angong Niuhuang Pill, shows promise in addressing pulmonary conditions. Using a comprehensive approach, combining network pharmacology analysis with experimental validation, this study explores the therapeutic effects and mechanisms of QKL against PF for the first time. In vivo, QKL reduced collagen deposition and suppressed proinflammatory cytokines in a bleomycin-induced PF mouse model. In vitro studies demonstrated QKL's efficacy in protecting cells from bleomycin-induced injury and reducing collagen accumulation and cell migration in TGF-ß1-induced pulmonary fibrosis cell models. Network pharmacology analysis revealed potential mechanisms, confirmed by western blotting, involving the modulation of PI3K/AKT and SRC/STAT3 signaling pathways. Molecular docking simulations highlighted interactions between QKL's active compounds and key proteins, showing inhibitory effects on epithelial damage and fibrosis. Collectively, these findings underscore the therapeutic potential of QKL in alleviating pulmonary inflammation and fibrosis through the downregulation of PI3K/AKT and SRC/STAT3 signaling pathways, with a pivotal role attributed to its active compounds.


Assuntos
Medicamentos de Ervas Chinesas , Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Transdução de Sinais , Colágeno/metabolismo , Colágeno/farmacologia , Colágeno/uso terapêutico , Fibrose , Bleomicina/efeitos adversos
7.
Pak J Med Sci ; 40(3Part-II): 467-472, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356806

RESUMO

Objective: To explore the changes of serum-related indexes at different time points, so as to identify the critical time of converting from simple premature thelarche (PT) to idiopathic central precocious puberty (ICPP). Methods: This is a retrospective study. The subjects of the study were 50 girls with PT who were admitted to the Children's Hospital of Hebei Province from January 2019 to September 2020. The enrolled 50 children were divided into the conversion group(n=12) and the non-conversion group(n=38) according to whether PT was converted into ICPP during follow-up. Furthermore, the levels of serum-related indexes and uterine and ovarian volumes were compared after the diagnosis of PT. Results: The IGF-1 and IGFBP-3 levels of children in the conversion group began to change significantly from six months after the diagnosis, with statistically significant differences when compared with the levels of children at the initial diagnosis, three months and those of the non-conversion group at the same time points (p<0.05). The levels of vitamin-D, DHEA and leptin began to change significantly at nine months after the diagnosis (p<0.05). Besides, uterine and ovarian volumes in the conversion group began to increase significantly six months after the diagnosis, with statistically significant differences when compared with those in the non-conversion group (p<0.05). Conclusion: Findings in our study suggest that regular monitoring of vitamin-D, IGF-1, IGFBP-3, DHEA and leptin levels, and uterine and ovarian volumes can predict the conversion from PT to ICPP at an early stage.

8.
Toxicol Appl Pharmacol ; 484: 116871, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423217

RESUMO

Salvia miltiorrhiza Bunge. (DS), as an important traditional Chinese medicine (TCM), has a long history of usage for promoting blood circulation and removing blood stasis. Modern studies have shown that the chemical components of DS have many biological activities such as cardiovascular protection, anti-arrhythmia, anti-atherosclerosis, improvement of microcirculation, protection of myocardium, inhibition and removal of platelet aggregation. Nevertheless, the action mechanism of DS as well its active compounds on platelet activation has not been fully uncovered. This study aimed to find out the potential targets and mechanisms of DS in the modulation of platelet activation and thrombosis, using network pharmacology and biological experimental. These compounds with anti-thrombotic activity in DS, cryptotanshinone (CPT), isoeugenol (ISO) and tanshinone IIA (TSA), together with the corresponding targets being Src, Akt and RhoA are screened by network pharmacology. We confirmed that ISO, CPT and TSA dose-dependently inhibited platelet activation in vitro, mainly by inhibiting agonist-induced clot retraction, aggregation and P-selectin and ATP release. The western blot findings indicated that ISO, CPT, and TSA led to reduced levels of p-Akt and p-ERK in activated platelets. Additionally, ISO and TSA were observed to decrease p-cSrc expression while increasing RhoA expression. ISO, CPT, and TSA demonstrated a potential to restrict the advancement of carotid arterial thrombosis in vivo. We confirm that ISO, CPT and TSA are the key anti-thrombotic active compounds in DS. These active compounds exhibit unique inhibitory effects on platelet activation and thrombus formation by modulating the Akt/ERK and cSrc/RhoA signaling pathways.


Assuntos
Salvia miltiorrhiza , Trombose , Salvia miltiorrhiza/química , Farmacologia em Rede , Proteínas Proto-Oncogênicas c-akt/farmacologia , Ativação Plaquetária , Trombose/tratamento farmacológico
10.
Plant Physiol ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377473

RESUMO

As a complex trait, C4 photosynthesis has multiple independent origins in evolution. Phylogenetic evidence and theoretical analysis suggest that C2 photosynthesis, which is driven by glycine decarboxylation in the bundle sheath cell, may function as a bridge from C3 towards C4 photosynthesis. However, the exact molecular mechanism underlying the transition between C2 photosynthesis towards C4 photosynthesis remains elusive. Here, we provide evidence suggesting a role of higher α-ketoglutarate (AKG) concentration during this transition. Metabolomic data of 12 Flaveria species, including multiple photosynthetic types, show that AKG concentration initially increased in the C3-C4 intermediate with a further increase in C4 species. Petiole feeding of AKG increases the concentrations of C4 related metabolites in C3-C4 and C4 species but not the activity of C4 related enzymes. Sequence analysis shows that glutamate synthase (Fd-GOGAT), which catalyzes the generation of glutamate using AKG, was under strong positive selection during the evolution of C4 photosynthesis. Simulations with a constraint-based model for C3-C4 intermediate further show that decreasing the activity of Fd-GOGAT facilitated the transition from a C2-dominant to a C4-dominant CO2 concentrating mechanism. All these results provide insight into the mechanistic switch from C3-C4 intermediate to C4 photosynthesis.

11.
Plant Physiol ; 194(4): 2400-2421, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38180123

RESUMO

Light-induced de-etiolation is an important aspect of seedling photomorphogenesis. GOLDEN2 LIKE (GLK) transcriptional regulators are involved in chloroplast development, but to what extent they participate in photomorphogenesis is not clear. Here, we show that ELONGATED HYPOCOTYL5 (HY5) binds to GLK promoters to activate their expression, and also interacts with GLK proteins in Arabidopsis (Arabidopsis thaliana). The chlorophyll content in the de-etiolating Arabidopsis seedlings of the hy5 glk2 double mutants was lower than that in the hy5 single mutant. GLKs inhibited hypocotyl elongation, and the phenotype could superimpose on the hy5 phenotype. Correspondingly, GLK2 regulated the expression of photosynthesis and cell elongation genes partially independent of HY5. Before exposure to light, DE-ETIOLATED 1 (DET1) affected accumulation of GLK proteins. The enhanced etioplast development and photosystem gene expression observed in the det1 mutant were attenuated in the det1 glk2 double mutant. Our study reveals that GLKs act downstream of HY5, or additive to HY5, and are likely quantitatively adjusted by DET1, to orchestrate multiple developmental traits during the light-induced skotomorphogenesis-to-photomorphogenesis transition in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação da Expressão Gênica de Plantas , Hipocótilo , Luz , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Plântula/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
Food Chem ; 438: 137993, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37992603

RESUMO

Aroma is one of the decisive factors affecting the quality and consumer acceptance of edible mushrooms. This review summarized the key components and formation pathways of edible mushroom aroma. It also elaborated on the affecting factors and emerging analytical strategies of edible mushroom aroma. A total of 1308 volatile organic compounds identified in edible mushrooms, 61 were key components. The formation of these compounds is closely related to fatty acid metabolism, amino acid metabolism, lentinic acid metabolism, and terpenoid metabolism. The aroma profiles of edible mushrooms were affected by genetic background, preharvest factors, and preservation methods. Molecular sensory science and omics techniques are emerging analytical strategies to reveal aroma information of edible mushrooms. This review would provide valuable data and insights for future research on edible mushroom aroma.


Assuntos
Agaricales , Compostos Orgânicos Voláteis , Agaricales/química , Odorantes , Vias Biossintéticas , Compostos Orgânicos Voláteis/química , Metabolismo dos Lipídeos
13.
World Neurosurg ; 181: e75-e83, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37532021

RESUMO

BACKGROUND: Treatment modalities of ependymoma in infants remain controversial. Postoperative adjuvant radiotherapy could prolong overall survival but has the potential to affect nervous system development in infants. The role of adjuvant chemotherapy in prolonging overall survival for infants with ependymoma is still unclear. Therefore we designed this study to explore the effect of treatment modalities on survival time of infants with ependymoma. METHODS: We studied 72 infants with ependymoma from the Surveillance, Epidemiology, and End Results database in this retrospective analysis. Univariate and multivariate Cox proportional hazard models were adopted to determine hazard ratios and compare overall survival. RESULTS: Among 72 infants with ependymoma, 35 were male (48.6%) and 37 were female (51.4%). The 5-year overall survival of all patients was 67%. Forty-six infants (63.9%) received gross total resection, 20 (27.8%) received subtotal resection, and 6 (8.3%) did not receive surgical resection or only autopsy. Twenty-one infants (29.2%) received radiotherapy, and 45 (62.5%) received chemotherapy. Multivariate analysis revealed that patients accepted surgical resection (No vs. gross total resection, P < 0.001; No vs. subtotal resection, P = 0.026) and chemotherapy (No vs. Yes, P = 0.024) are the independent prognostic factors for overall survival. CONCLUSIONS: Treatment modality is associated with survival time in infants with ependymoma. The extent of resection and chemotherapy were independent prognostic factors for infants with ependymoma.


Assuntos
Neoplasias Encefálicas , Ependimoma , Lactente , Humanos , Masculino , Feminino , Estudos Retrospectivos , Radioterapia Adjuvante/métodos , Terapia Combinada , Quimioterapia Adjuvante , Resultado do Tratamento , Neoplasias Encefálicas/terapia
14.
Semin Cell Dev Biol ; 155(Pt A): 3-9, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36858897

RESUMO

Maintaining proper metabolite levels in a complex metabolic network is crucial for maintaining a high flux through the network. In this paper, we discuss major regulatory mechanisms over the Calvin Benson Cycle (CBC) with regard to their roles in conferring homeostasis of metabolite levels in CBC. These include: 1) Redox regulation of enzymes in the CBC on one hand ensures that metabolite levels stay above certain lower bounds under low light while on the other hand increases the flux through the CBC under high light. 2) Metabolite regulations, especially allosteric regulations of major regulatory enzymes, ensure the rapid up-regulation of fluxes to ensure sufficient amount of triose phosphate is available for end product synthesis and concurrently avoid phosphate limitation. 3) A balanced activities of enzymes in the CBC help maintain balanced flux through CBC; some innate product feedback mechanisms, in particular the ADP feedback regulation of GAPDH and F6P feedback regulation of FBPase, exist in CBC to achieve such a balanced enzyme activities and hence flux distribution in the CBC for greater photosynthetic efficiency. Transcriptional regulation and natural variations of enzymes controlling CBC metabolite homeostasis should be further explored to maximize the potential of engineering CBC for greater efficiency.


Assuntos
Fosfatos , Fotossíntese , Fotossíntese/fisiologia
15.
Food Res Int ; 175: 113790, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38129010

RESUMO

To increase the anti-digestion ability of extruded rice starch (ERS), the influence of rice glutelin (RG) on digestive and structural characteristics of ERS were investigated. The resistant starch content increased from 4.49 % to 18.08 % as the RG content increased, while the digestion rate and digestion velocity constant were reduced by the incorporation of RG. Morphological observations showed that ERS was adhered and encapsulated by RG, and the specific area of starch granules were decreased after the addition of RG. The results of XRD and FTIR suggested that the long-range and short-range orders of ERS were improved due to the complexation with RG. The thickness of crystalline of ERS was increased while its amorphous region thickness was reduced by the supplementation with RG. The 1H NMR and 13C NMR data revealed that the branching degree and double helix content of ERS was increased by 46.24 % and 52.67 % when RG content reached to 12 %. Additionally, the addition of RG altered the molecular weight and chain length distribution of ERS. The α-amylase activity and glucoamylase activity was inhibited by RG. These results could provide a valuable basis for the application of RG in extruded rice starchy foods with lower glycemic index.


Assuntos
Oryza , Amido , Amido/química , Oryza/química , Glutens/metabolismo , Digestão , Índice Glicêmico
16.
New Phytol ; 241(1): 82-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872738

RESUMO

C4 plants typically operate a CO2 concentration mechanism from mesophyll (M) cells into bundle sheath (BS) cells. NADH dehydrogenase-like (NDH) complex is enriched in the BS cells of many NADP-malic enzyme (ME) type C4 plants and is more abundant in C4 than in C3 plants, but to what extent it is involved in the CO2 concentration mechanism remains to be experimentally investigated. We created maize and rice mutants deficient in NDH function and then used a combination of transcriptomic, proteomic, and metabolomic approaches for comparative analysis. Considerable decreases in growth, photosynthetic activities, and levels of key photosynthetic proteins were observed in maize but not rice mutants. However, transcript abundance for many cyclic electron transport (CET) and Calvin-Benson cycle components, as well as BS-specific C4 enzymes, was increased in maize mutants. Metabolite analysis of the maize ndh mutants revealed an increased NADPH : NADP ratio, as well as malate, ribulose 1,5-bisphosphate (RuBP), fructose 1,6-bisphosphate (FBP), and photorespiration intermediates. We suggest that by optimizing NADPH and malate levels and adjusting NADP-ME activity, NDH functions to balance metabolic and redox states in the BS cells of maize (in addition to ATP supply), coordinating photosynthetic transcript abundance and protein content, thus directly regulating the carbon flow in the two-celled C4 system of maize.


Assuntos
Carbono , NADH Desidrogenase , Carbono/metabolismo , NADH Desidrogenase/metabolismo , Zea mays/genética , Zea mays/metabolismo , Malatos/metabolismo , NADP/metabolismo , Dióxido de Carbono/metabolismo , Proteômica , Fotossíntese , Oxirredução , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Folhas de Planta/metabolismo
17.
Plant Direct ; 7(12): e549, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38054113

RESUMO

The mesophyll cells of grass leaves, such as rice, are traditionally viewed as displaying a relatively uniform pattern, in contrast to the clear distinctions of palisade and spongy layers in typical eudicot leaves. This quantitative analysis of mesophyll cell size and shape in rice leaves reveals that there is an inherent pattern in which cells in the middle layer of the mesophyll are larger and less circular and have a distinct orientation of their long axis compared to mesophyll cells in other layers. Moreover, this pattern was observed in a range of rice cultivars and species. The significance of this pattern with relation to potential photosynthetic function and the implication of the widespread use of middle layer mesophyll cells as typical of the rice leaf have been investigated and discussed.

19.
Mayo Clin Proc ; 98(11): 1660-1669, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37923523

RESUMO

OBJECTIVE: To evaluate whether abdominal compression significantly increased the total enteroscopy rate in single-balloon enteroscopy (SBE). METHODS: Consecutive patients who underwent SBE at 2 hospitals were prospectively included between June 1, 2020, and September 30, 2021. They were randomly divided into an abdominal compression group and a non-abdominal compression group with use of sealed envelopes generated by a computer. Total enteroscopy rates were compared between the groups. RESULTS: The study included 200 patients. The total enteroscopy rates were 73% and 16% in the abdominal compression and non-abdominal compression groups, respectively (relative risk, 13.55; 95% CI, 6.79 to 27.00; P<.001). The total enteroscopy rate was higher in the 70 patients who were identified to have undergone no previous abdominal surgery or small intestinal stenosis than in the 32 patients who had undergone such procedures in the abdominal compression group (84% vs 47%; relative risk, 6.08; 95% CI, 2.36 to 15.67; P<.001). Relevant positive findings were not significantly different between the groups (58% vs 45%; P=.07). Binary logistic regression analysis found abdominal compression to be associated with a better total enteroscopy rate (odds ratio, 16.68; 95% CI, 7.92 to 35.15; P<.001), and the presence of previous abdominal surgery or small intestinal stenosis was associated with difficulty in completing the total enteroscopy procedure (odds ratio, 0.26; 95% CI, 0.12 to 0.58; P<.01). CONCLUSION: Abdominal compression significantly increased the total enteroscopy rate in SBE. Complete total enteroscopy may be challenging in patients with a history of abdominal surgery or small intestinal stenosis.


Assuntos
Enteropatias , Enteroscopia de Balão Único , Humanos , Constrição Patológica , Endoscopia Gastrointestinal/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...