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1.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801148

RESUMO

Chemotherapeutics are the mainstay treatment for metastatic breast cancers. However, the chemotherapeutic failure caused by multidrug resistance (MDR) remains a pivotal obstacle to effective chemotherapies of breast cancer. Although in vitro evidence suggests that the overexpression of ATP-Binding Cassette (ABC) transporters confers resistance to cytotoxic and molecularly targeted chemotherapies by reducing the intracellular accumulation of active moieties, the clinical trials that target ABCB1 to reverse drug resistance have been disappointing. Nevertheless, studies indicate that ABC transporters may contribute to breast cancer development and metastasis independent of their efflux function. A broader and more clarified understanding of the functions and roles of ABC transporters in breast cancer biology will potentially contribute to stratifying patients for precision regimens and promote the development of novel therapies. Herein, we summarise the current knowledge relating to the mechanisms, functions and regulations of ABC transporters, with a focus on the roles of ABC transporters in breast cancer chemoresistance, progression and metastasis.

2.
Biosens Bioelectron ; 182: 113169, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33799027

RESUMO

Signal amplification is one of the most effective ways to develop the high-performance electrochemical sensors. However, it can be more complicated for ratiometric detections. Herein, a ratiometric electrochemical aptasensor for aflatoxin B1 (AFB1) was proposed by taking advantage of a dual-amplification strategy by coupling of DNA walker (DW) with hybridization chain reaction (HCR). The special binding of AFB1 with ferrocene (Fc)-labelled aptamer triggers DW on hairpin DNA (hDNA) tracks to produce abundant double-stranded DNA (dsDNA). HCR-based strand amplification occurs on these dsDNA to absorb more methylene blue (MB). Then current ratio of MB (IMB) and Fc (IFc) is designed as a yardstick to detect AFB1. Our experiments reveal that the interaction between Fc and MB (i.e., steric hindrance, electron mediator) varies. In addition to steric hindrance, the presence of MB also acts as electron mediator, thereby facilitating the electron transfer between Fc and electrode. Such combined effect consequently depresses the efficiency of dual-amplification strategy to improve the detection. The developed ratiometric electrochemical aptasensor allows the accurate detection of AFB1 in the 0.003-3 pg mL-1 range. Our work has shed light on the amplification strategy for ratiometric sensing, and provided a new route in integrating different amplification strategies.

3.
Med Sci Monit ; 27: e932346, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33820903

RESUMO

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures.Reference:Yong Xiong, Yi-Jia Xiong, Dong-Yang Liu, Rong-Rong Shen: Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest.Med Sci Monit 2019; 25:6015-6022. 10.12659/MSM.916116.

4.
J Integr Neurosci ; 20(1): 67-75, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33834692

RESUMO

Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer's disease. The present paper's goal was to explore the potential mechanisms of geniposide to protect against Alzheimer's disease. We treated the human neuroblastoma SH-SY5Y cell line with Aß1-42 as an Alzheimer's disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer's disease. Further, SH-SY5Y cells damaged by Aß1-42 were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against Aß1-42-induced toxicity. Results showed that Akt and mTOR's geniposide inhibited phosphorylation induced by Aß1-42, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aß1-42. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aß toxicity.

5.
Sci Total Environ ; 782: 146874, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33848858

RESUMO

Low-frequency high-magnitude storms can flush disproportionate amounts of terrigenous dissolved organic carbon (DOC) and particulate organic carbon (POC) into rivers during a short period. However, previous studies focused on the impacts of storms on organic carbon transport in headwater streams that are minimally influenced by human activities and are far from lakes. To better estimate the lake carbon budget and manage lake water environments, we need to understand the transport of storm-induced organic carbon into lakes by eutrophic rivers. Based on daily and hourly time-series monitoring data, this paper systematically studied the influences of storm precipitation on DOC and POC transport in the eutrophic Tiaoxi River entering Lake Taihu, the 3rd largest freshwater lake in China. The results showed that seven storms transported 59% of the annual total organic carbon into Lake Taihu in 2019, and all storms resulted in transport peaks. During the storm period on August 9-16, 2019, DOC was negatively related to the water level (r = -0.44, p < 0.05), but POC responded positively (r = 0.52, p < 0.05); allochthonous organic carbon contents were elevated, but the autochthonous components were diluted. Moreover, the storm-induced input of riverine organic carbon influenced the lake water environment across a large region, and the impacts lasted more than 10 days. These findings have important implications for accurately estimating riverine organic carbon fluxes into lakes and making better-informed decisions about when to pump drinking water from lakes.

6.
Ann Palliat Med ; 10(3): 3343-3353, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849119

RESUMO

BACKGROUND: Symmetrical dimethylarginine (ADMA) endogenously inhibits nitric oxide synthase (NOS) and strongly indicates oxidant stress, whose formation primarily derived from type 1 protein arginine N-methyltransferase (PRMT1) and whose metabolism was governed by type 1 dimethylarginine dimethylaminohydrolase (DDAH1). This study aimed to evaluate participation of the PRMT1-ADMA-DDAH1 metabolism axis in the kidneys of type 2 diabetes model rats and human subjects, and the effect of probucol on this axis and renal function. METHODS: A total of 30 rats were randomly assigned to a normal group (NC, n=10), diabetic group (DM, n=10), and a diabetics under probucol treatment group (PM, n=10). Throughout 8 weeks of probucol treatment, plasma NOS, the malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and catalase (CAT) activity were evaluated by chemical colorimetric approach. ADMA concentration was evaluated with an enzyme-linked immunosorbent assay (ELISA) and analysis of expression of PRMT1 and DDAH1 in kidneys with reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blotting were performed. RESULTS: The expression of DDAH1 in the kidney, and the plasma NOS, NO, SOD, and CAT activities in diabetic group were lower, while MDA and the expression of PRMT1 and ADMA were higher in contrast to the control group. In diabetics rats receiving probucol, the expressions of DDAH1 and ADMA were downregulated, whereas that of PRMT1 was upregulated. Probucol inhibited the indexes of oxidative stress and improved the kidney function in both diabetic rats and humans. CONCLUSIONS: We found that the expression of the PRMT1-ADMA-DDAH1 axis was altered in the kidneys of diabetic rats. Moreover, results indicated that probucol therapy regulates expression at both ends of this axis, which may preserve renal function by reducing oxidant stress. Therefore, probucol may partially restore expression of the PRMT1-ADMA-DDAH1 axis in diabetic kidneys, immigrate oxidant stress, and enhance renal function.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33852023

RESUMO

Biofilms are a form of microbial community that can be beneficial for industrial fermentation because of their remarkable environmental resistance. However, the mechanism of biofilm formation in Saccharomyces cerevisiae remains to be fully explored, and this may enable improved industrial applications for this organism. Although quorum-sensing (QS) molecules are known to be involved in bacteria biofilm formation, few studies have been undertaken with these in fungi. 2-phenylethanol (2-PE) is considered a QS molecule in S. cerevisiae. Here, we found that exogenous 2-PE could stimulate biofilm formation at low cell concentrations. ARO8p and ARO9p are responsible for the synthesis of 2-PE and were crucial to the formation of biofilm. Deletion of the ARO8 and ARO9 genes reduced the content of 2-PE in the early stage of fermentation, reduced ethanol yield and decreased biofilm formation. The expression of FLOp, which is involved in cell adhesion, and the content of extracellular polysaccharides of mutant strains ΔARO8 and ΔARO9 were also significantly reduced. These findings indicate that the production of 2-PE had a positive effect on biofilm formation in S. cerevisiae, thereby providing further key details for studying the formation of biofilm mechanism in the future. KEY POINTS: • Quorum-sensing molecule 2-PE positively affects biofilm formation in S. cerevisiae. • 2-PE synthetic genes ARO8 and ARO9 deletion reduced extracellular polysaccharide. • ARO8 and ARO9 deletion reduced the gene expression of the FLO family.

8.
Indian Pediatr ; 58(3): 280-281, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33713066

RESUMO

We report on 16 children with ingestion of magnetic foreign bodies, who were identified by a medical record review of our hospital data for the time period between January, 2017 and May, 2018. Digestive tract wall was sandwiched in 13 (75%) children and 11 (74%) had gaptic intestinal perforation.

9.
Water Environ Res ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780582

RESUMO

The most effective pretreatment method for the detection of dissolved organic nitrogen (DON) is the nanofiltration (NF) by effectively intercepting DON into the concentrated solution, thus increasing the proportion of DON in solution so that achieving accurate detection of DON. The existing NF pretreatment technology for detection of DON has the problem of low accuracy and unclear separation mechanism of mass transfer upon the NF membranes. Based on the problems of NF membrane, the polyether sulfone (PES) composite NF membrane was modified by mesoporous carbon and the basic performance parameters of the modified PES composite NF membrane were characterized by Static contact angle (SCA), Zeta potential, and X-ray photoelectron spectroscopy (XPS). The results show that the optimum doping amount of mesoporous carbon is in the range of 0.5%-1.0%. Furthermore, the pore size of NF membrane could be controlled effectively by changing doping amount of mesoporous carbon, so as to guide the improvement of membrane pore structure. After the pretreatment of mesoporous material modified PES composite NF membrane, the ratio of dissolved inorganic nitrogen (DIN)/total dissolved nitrogen (TDN) could be reduced to 0.55-0.65 and the pretreatment effect was also affected by screening effect and electrostatic effect. The best retention performance of amino acids is the 1.0%C modified membrane which retention rate of the amino acid is between 32.3% and 94.7%, and the membrane loss of the four amino acids is much smaller than other membranes. The mass transfer process of NF membrane was simulated by steric-hindrance pore (SHP) model, Teorell-Meyer-Sievers (TMS) model, and Electrostatic Steric-hindrance (ES) model respectively. According to the simulation software designed by ourselves, the dominant effects of screening and electrostatic effects are simultaneously affected by the pore structure of membranes and the size of the contaminant molecules. PRACTITIONER POINTS: The feasibility of mesoporous carbon with modified PES composite nanofiltration membrane pretreatment for DON measurement in comparison to pure NF membranes was investigated. The ability of modified PES composite NF membrane with different molecular weight of DON and the relationship between pore radius of membrane and interception pollutant molecular size was discussed. The influence of screening effect and electrostatic effect on the retention of pollutants was discussed by the SHP model, TMS model and ES model; the simulation software interface is designed and the calculation process of the model is simulated by computer.

11.
J Org Chem ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769061

RESUMO

Electrochemistry has been successfully applied in metal catalysis to avoid the usage of chemical redox agents. This strategy proved to be a powerful approach to construct carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. However, most of the developed methods are based on either anodic oxidation or cathodic reduction, in which a sacrificial reaction occurs at the counter electrode. Paired electrolysis merging with metal catalysis is underdeveloped, wherein both anodic and cathodic processes are taking place simultaneously. Herein, we demonstrated that by using esterification of carboxylic acids with aryl halides via paired electrolysis using nickel as the catalyst the respective aryl esters were obtained in good to excellent yields at room temperature in an undivided electrochemical cell.

12.
J Sch Health ; 91(5): 370-375, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33768584

RESUMO

BACKGROUND: In fall 2020, all public K-12 schools reopened in broadly 3 learning models. The hybrid model was considered a mid-risk option compared with remote and in-person learning models. The current study assesses school-based coronavirus disease 2019 (COVID-19) spread in the early fall using a national data set. METHODS: We assess COVID-19 case growth rates from August 10 to October 14, 2020 based on a crowdsourcing data set from the National Education Association. The study follows a retrospective cohort design with the baseline exposures being 3 teaching models: remote learning only, hybrid, and in-person learning. To assess the consistency of our findings, we estimated the overall, as well as region-specific (Northeast, Midwest, South, and West) and poverty-specific (low, mid, and high) COVID-19 case-growth rates. In addition, we validated our study sample using another national sample survey data. RESULTS: The baseline was from 617 school districts in 48 states, where 47% of school districts were in hybrid, 13% were in remote, and 40% were in-person. Controlling for state-level risk and rural-urban difference, the case growth rates for remote and in-person were lower than the hybrid (odds ratio [OR]: 0.963, 95% confidence interval [CI]: 0.960-0.965 and OR: 0.986, 95% CI: 0.984-0.988, respectively). A consistent result was found among school districts in all 4 regions and each poverty level. CONCLUSIONS: Hybrid may not necessarily be the next logical option when transitioning from the remote to in-person learning models due to its consistent higher case growth rates than the other 2 learning models.

13.
ACS Infect Dis ; 7(4): 884-893, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33653026

RESUMO

Antibiotic resistance nowadays is spreading much faster than the introduction of new antibiotics into clinical practice. There is an urgent need for potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi provide a promising source for chemical diversity with antibiotic-like molecules. To identify structurally distinct compounds that effectively eradicate MDR pathogens and to control the development of antibiotic resistance, we have reinvestigated equisetin, a previously reported meroterpenoid isolated from a marine sponge-derived fungus. Equisetin exerted efficient antibacterial activities against either MRSA or VRE without detectable high-level resistance. Meanwhile, equisetin, as an antibiotic adjuvant, restores colistin susceptibility to colistin-resistant bacteria toward diverse Gram-negative pathogens. Intriguingly, the low-level equisetin-resistant Staphylococcus aureus displayed collateral sensitivity to multiple classes of existing antibiotics with decreased capacity to produce biofilm. Lastly, equisetin showed efficacy with MRSA in three infected animal models. This work suggests that equisetin derived from marine natural products is a promising lead to overcome antibiotic resistance, providing new insight in future antibiotic discovery and development.

14.
Life Sci ; 276: 119367, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33775691

RESUMO

BACKGROUNDS: Estrogen and its metabolites often lead to intrahepatic cholestasis in susceptible women with pregnancy, administration of oral contraceptives and postmenopausal hormone replacement therapy. Recently, dysfunction of the gut-liver axis has been suggested to play a pivotal role in the progression of cholestasis, but details about estrogen cholestasis (EC)-induced gut and liver injury are still largely unknown. This study aims to gain insight into EC-induced gut and liver injury and cell signaling implicated. METHODS: Male rats were exposed to 5 and 10 mg/kg of 17α-ethinylestradiol via subcutaneous injection for 5 successive days to simulate human EC. RESULTS: By detection of these estrogen cholestatic rats, we found that EC induced inflammation in the liver but not in the intestine through activating NF-κB signaling pathway. EC strongly induced oxidative stress in both the liver and intestine, and activated the hepatic Nrf2/Gclm/Gclc pathway and the intestinal Nrf2/Ho-1 pathway, respectively, for adaptively regulating oxidative stress. EC increased cell apoptosis in both the liver and intestine. Additionally, EC elevated phosphorylation of Akt, ERK1/2, and p38 in the liver and increased phosphorylation of p38 in the intestine. CONCLUSIONS: EC induces liver inflammation, both gut and liver oxidative stress and apoptosis, involving in activating PI3K/Akt and MAPK signaling pathways. Investigation of EC-induced gut and liver injury contributes to the development of new potential therapeutic strategies.

15.
Am J Chin Med ; 49(3): 677-703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704029

RESUMO

To investigate the therapeutic efficacy of Scutellarin (SCU) on neurite growth and neurological functional recovery in neonatal hypoxic-ischemic (HI) rats. Primary cortical neurons were cultured to detect the effect of SCU on cell viability of neurons under oxygen-glucose deprivation (OGD). Double immunofluorescence staining of Tuj1 and TUNEL then observed the neurite growth and cell apoptosis in vitro,and double immunofluorescence staining of NEUN and TUNEL was performed to examine the neuronal apoptosis and cell apoptosis in brain tissues after HI in vivo. Pharmacological efficacy of SCU was also evaluated in HI rats by neurobehavioral tests, triphenyl tetrazolium chloride staining, Hematoxylin and eosin staining and Nissl staining. Astrocytes and microglia expression in damaged brain tissues were detected by immunostaining of GFAP and Iba1. A quantitative real-time polymerase chain reaction and western blot were applied to investigate the genetic expression changes and the protein levels of autophagy-related proteins in the injured cortex and hippocampus after HI. We found that SCU administration preserved cell viability, promoted neurite outgrowth and suppressed apoptosis of neurons subjected to OGD both in vitroand in vivo. Meanwhile, 20 mg/kg SCU treatment improved neurological functions and decreased the expression of astrocytes and microglia in the cortex and hippocampus of HI rats. Additionally, SCU treatment depressed the elevated levels of autophagy-related proteins and the p75 neurotrophin receptor (p75NTR) in both cortex and hippocampus. This study demonstrated the potential therapeutic efficacy of SCU by enhancing neurogenesis and restoring long-term neurological dysfunctions, which might be associated with p75NTR depletion in HI rats.

16.
Healthc (Amst) ; 9(2): 100530, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33652295

RESUMO

We report the successful implementation of a modified Traffic Control Bundling (TCB) protocol called "Red, Yellow and Green" on the inpatient medical units at St. Paul's Hospital in Vancouver, Canada during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. The modified TCB protocol demonstrates an important example on how hospitals can rapidly reorganize operational and clinical processes to reallocate existing capacity to minimize exposure, improve traffic flow and reduce nosocomial transmissions of COVID-19 to health care workers (HCWs) and other patients. Preliminary evidence demonstrates the benefits on how an existing facility can be redesigned for adjustable ward capacity to provide disease containment under a context of uncertainty of disease transmission and varying patient load. Important lessons in preparation for the evolution of the pandemic fall into categories of risk management, capacity and demand management.

17.
J Integr Plant Biol ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710755

RESUMO

Phosphorus is an essential macronutrient for plant growth and development. Root system architecture (RSA) affects a plant's ability to obtain phosphate, the major form of phosphorus that plants uptake. In this review, I first consider the relationship between RSA and plant phosphorus-acquisition efficiency, describe how external phosphorus conditions both induce and impose changes in the RSA of major crops and of the model plant Arabidopsis, and discuss whether shoot phosphorus status affects RSA and whether there is a universal root developmental response across all plant species. I then summarize the current understanding of the molecular mechanisms governing root developmental responses to phosphorus deficiency. I also explore the possible reasons for the inconsistent results reported by different research groups and comment on the relevance of some studies performed under laboratory conditions to what occurs in natural environments. This article is protected by copyright. All rights reserved.

18.
Aging (Albany NY) ; 132021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744855

RESUMO

The regulation of mTOR and the dimethylation of histone H3 on lysine 9 (H3K9me2) H3K9me2 by Uhrf1 and the mechanism of autophagy regulation in myocardial ischemia-reperfusion injury (MIRI) were studied in vivo and in vitro. An in vitro I/R injury model was established using the primary mouse cardiomyocytes treated with H2O2. Subsequent analysis by qRT-PCR, western blot, and immunofluorescence indicated that overexpression of Uhrf1 significantly inhibited apoptosis of the H2O2-treated cardiomyocytes, reduced expression of apoptosis factors caspase-3 and Bax, and increased expression of apoptosis inhibitory factor Bcl-2. Furthermore, Uhrf1 was found to increase cardiomyocyte proliferation and promote the expression of mTOR, while the four expression peaks of H3K9me2 on the mTOR gene were inhibited by overexpression of Uhrf1. The expression of autophagy factors LC3, Beclin-1, and p-mTOR in Uhrf1-overexpressed cardiomyocytes was dramatically increased, and P62 expression was dramatically decreased. When an H3K9me2 inhibitor was added to the Uhrf1-knockdown cardiomyocytes, the expression of mTOR was increased, the expression of LC3, Beclin-1, and p-mTOR was decreased, and P62 expression was significantly increased. In the present study, Uhrf1 exhibits a protective function in MIRI, reducing the apoptosis of cardiomyocytes while increasing their proliferation and viability.

19.
Opt Express ; 29(3): 4464-4474, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33771024

RESUMO

Simultaneous measurement of lidar and radar signals returned from the same cirrus clouds is a prospective method for retrieving the cloud microphysics, i.e. size and shape of the ice crystals constituting the clouds. In this study, the ratio of the backscattered signals of lidar and radar called the radar-lidar ratio has been calculated for the first time for typical shapes of ice crystals and wide distribution of the crystals over their sizes. It is shown that it is the lidar-radar ratio that is most sensitive to crystal sizes while the lidar depolarization ratio is most sensitive to crystal shapes.

20.
J Biomed Nanotechnol ; 17(2): 242-252, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33785095

RESUMO

Sericin, a silk protein, has a high potential for use as an extracellular matrix in tissue engineering applications. In this study, novel gelatin (GEL) and silk sericin (SS) were incorporated with a polyvinyl alcohol) PVA hydrogel nanocomposite (GEL-SS-PVA) scaffold that can be applied to repair cartilage. Glutaraldehyde was used as a cross-linking agent, with hydrochloric acid acting as an initiator. The microstructure characteristics of the obtained GEL-SS and GEL-SS-PVA scaffolds were also examined using FTIR and XRD spectra and their enhanced thermal stability was assessed by TGA. The blended GEL-SS and GEL-SS-PVA scaffolds were confirmed by SEM analysis to be highly porous with optimum pore sizes of 172 and 58 µm, respectively. Smaller pore sizes and improved uniformity were observed as the concentration of PVA in the GEL-SS-PVA scaffold increased. PVA decreased the tensile strength and elongation of the membranes but increased the modulus. Swelling studies showed high swellability and complete degradation in the presence of phosphate-buffered saline. Cytocompatibility of the GEL-SS-PVA scaffolds showed that these had the highest potential to promote cell proliferation as evaluated with standard microscopy using L929 fibroblasts. The prepared GEL-SS composite scaffold incorporated with the PVA hydrogel was implanted in full-thickness articular cartilage defects in rats. The repair effect of cartilage defects was observed and evaluated among the GEL-SS-PVA, GEL-SS, and control operation groups. The defects were almost completely repaired after 14 weeks in the GEL-SS-PVA group, thereby indicating that the GEL-SS-PVA composite had a favorable effect on articular cartilage defects in rat knee joint repair.


Assuntos
Cartilagem Articular , Nanocompostos , Sericinas , Animais , Gelatina , Hidrogéis , Articulação do Joelho , Álcool de Polivinil , Ratos , Seda , Engenharia Tecidual , Tecidos Suporte
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