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1.
Bioact Mater ; 19: 666-677, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35600979

RESUMO

An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.

2.
Chem Sci ; 13(32): 9265-9270, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36092999

RESUMO

We uncovered an asymmetric higher-order [10 + 2] cycloaddition reaction between diverse activated alkenes and a new type of π-allylpalladium complex-containing dipole-type 10π-cycloaddend, which was generated in situ from 2-methylene-1-indanols via a dehydrative insertion and deprotonation strategy under double activation of Pd(0) and phosphoric acid. A similar strategy was applied to an asymmetric higher-order [10 + 8] cycloaddition reaction or [10 + 4] cycloaddition reaction by using a heptafulvene derivative or a cyclic enone, respectively, as the acceptor. A variety of polycyclic frameworks imbedding an indene core were generally furnished in moderate to excellent yields with high levels of enantioselectivity by employing a newly designed chiral phosphoramidite ligand.

3.
BMC Med Imaging ; 22(1): 157, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057576

RESUMO

OBJECTIVES: We aimed to investigate the value of performing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) radiomics for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) based on multiple sequences. METHODS: We randomly allocated 165 patients with HCC who underwent partial hepatectomy to training and validation sets. Stepwise regression and the least absolute shrinkage and selection operator algorithm were used to select significant variables. A clinicoradiological model, radiomics model, and combined model were constructed using multivariate logistic regression. The performance of the models was evaluated, and a nomogram risk-prediction model was built based on the combined model. A concordance index and calibration curve were used to evaluate the discrimination and calibration of the nomogram model. RESULTS: The tumour margin, peritumoural hypointensity, and seven radiomics features were selected to build the combined model. The combined model outperformed the radiomics model and the clinicoradiological model and had the highest sensitivity (90.89%) in the validation set. The areas under the receiver operating characteristic curve were 0.826, 0.755, and 0.708 for the combined, radiomics, and clinicoradiological models, respectively. The nomogram model based on the combined model exhibited good discrimination (concordance index = 0.79) and calibration. CONCLUSIONS: The combined model based on radiomics features of Gd-EOB-DTPA enhanced MRI, tumour margin, and peritumoural hypointensity was valuable for predicting HCC microvascular invasion. The nomogram based on the combined model can intuitively show the probabilities of MVI.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos
5.
J Colloid Interface Sci ; 629(Pt A): 1-10, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36049324

RESUMO

HYPOTHESIS: Self-assembly of peptides is influenced by both molecular structure and external conditions, which dictate the delicate balance of different non-covalent interactions that driving the self-assembling process. The shifting of terminal charge residue is expected to influence the non-covalent interactions and their interplay, thereby affecting the morphologies of self-assemblies. Therefore, the morphology transition can be realized by shifting the position of the terminal charge residue. EXPERIMENTS: The structure transition from thin nanofibers to giant nanotubes is realized by simply shifting the C-terminal lysine of ultrashort Ac-I3K-NH2 to its N-terminus. The morphologies and detailed structure information of the self-assemblies formed by these two peptides are investigated systemically by a combination of different experimental techniques. The effect of terminal residue on the morphologies of the self-assemblies is well presented and the underlying mechanism is revealed. FINDINGS: Giant nanotubes with a bilayer shell structure can be self-assembled by the ultrashort peptide Ac-KI3-NH2 with the lysine residue close to the N-terminal. The Ac-KI3-NH2 dimerization through intermolecular C-terminal H-bonding promotes the formation of a bola-form geometry, which is responsible for the wide nanotube assembly formation. The evolution process of Ac-KI3-NH2 nanotubes follows the "growing width" model. Such a morphological transformation with the terminal lysine shift is applicable to other analogues and thus provides a facile approach for the self-assembly of wide peptide nanotubes, which can expand the library of good template structures for the prediction of peptide nanostructures.

6.
Chemistry ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36082763

RESUMO

In this study, a novel La(III)-based two-dimensional (2-D) metal-organic framework, [La 2/3 (qptca) 1/2 ] (referred to as SLX-2), from LaCl 3 and 1,1':4',1'':4'',1''':4''',1''''-quinquephenyl]-2,2'',2'''',5''-tetracarboxylic acid (H 4 qptca) was synthesized by conventional solvothermal method and thoroughly characterized using X-ray single crystal diffraction, powder X-ray diffraction, and thermogravimetric analyses. The 2-D SLX-2 features a unique lanthanum center exposed to the skeleton and then was used as an efficient Lewis acid catalyst for the Friedel-Crafts alkylation of indole and pyrrole with ß-nitrostyrene along with a wide substrate scope, giving the desired products in good to high yields under the optimal reaction conditions. Furthermore, the catalyst was used for twenty cycles, with nearly no effect on its activity, and the reaction was heterogeneous in nature. Moreover, compared to the previous hydrogen-bond-donating MOF catalysts for such alkylation reactions, SLX-2 showed an excellent stability toward harsh acidic and basic environment, and gave comparable catalytic activities.

7.
Cell Rep ; 40(12): 111361, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36130501

RESUMO

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.


Assuntos
Células da Medula Óssea , Medula Óssea , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Receptores de Serotonina/metabolismo , Fosfolipases Tipo C/metabolismo
8.
Biomaterials ; 289: 121801, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36137416

RESUMO

Iodine-125 (125I) brachytherapy has become one of the most effective palliative treatment options for advanced esophageal cancer. However, resistance toward 125I brachytherapy caused by pre-existing tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) signaling pathway activation represents a significant limitation in esophageal cancer treatment. To circumvent these problems, herein, we proposed an innovative strategy to alleviate radioresistance of brachytherapy by co-encapsulating catalase (CAT) and HIF-1 inhibitor-acriflavine (ACF) into the hydrophilic cavities of liposome, termed as "ACF-CAT@Lipo". Under overexpressed H2O2 stimulation in the tumor region, the fabricated ACF-CAT@Lipo can generate an amount of O2 and alleviate tumor hypoxia in vitro and in vivo. Furthermore, cooperating with ACF, the expression of hypoxia-related protein (e.g. HIF-1α, VEGF, MMP-2) are obviously decreased. Importantly, the copious oxygenation and the significant inhibition expression of HIF-1α can further improve the radiosensitivity of 125I brachytherapy and finally realize the eradication of esophageal cancer in vivo. The oxygen enrichment and HIF-1 inhibition function of ACF-CAT@Lipo provides a new strategy to overcome the brachytherapy resistance of esophageal cancer therapy.

9.
Nat Commun ; 13(1): 5128, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050300

RESUMO

The decline of CD8+ T cell functions contributes to deteriorating health with aging, but the mechanisms that underlie this phenomenon are not well understood. We use single-cell RNA sequencing with both cross-sectional and longitudinal samples to assess how human CD8+ T cell heterogeneity and transcriptomes change over nine decades of life. Eleven subpopulations of CD8+ T cells and their dynamic changes with age are identified. Age-related changes in gene expression result from changes in the percentage of cells expressing a given transcript, quantitative changes in the transcript level, or a combination of these two. We develop a machine learning model capable of predicting the age of individual cells based on their transcriptomic features, which are closely associated with their differentiation and mutation burden. Finally, we validate this model in two separate contexts of CD8+ T cell aging: HIV infection and CAR T cell expansion in vivo.


Assuntos
Linfócitos T CD8-Positivos , Infecções por HIV , Envelhecimento/genética , Linfócitos T CD8-Positivos/metabolismo , Estudos Transversais , Infecções por HIV/genética , Infecções por HIV/metabolismo , Humanos , Transcriptoma
10.
Nat Commun ; 13(1): 5540, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130959

RESUMO

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC.


Assuntos
Extinção Psicológica , Medo , Animais , Extinção Psicológica/fisiologia , Medo/fisiologia , Masculino , Camundongos , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia
11.
J Fungi (Basel) ; 8(9)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36135640

RESUMO

Purine nucleotides are indispensable compounds for many organisms and participate in basic vital activities such as heredity, development, and growth. Blocking of purine nucleotide biosynthesis may inhibit proliferation and development and is commonly used in cancer therapy. However, the function of the purine nucleotide biosynthesis pathway in the pathogenic fungus Magnaporthe oryzae is not clear. In this study, we focused on the de novo purine biosynthesis (DNPB) pathway and characterized MoAde8, a phosphoribosylglycinamide formyltransferase, catalyzing the third step of the DNPB pathway in M. oryzae. MoAde8 was knocked out, and the mutant (∆Moade8) exhibited purine auxotroph, defects in aerial hyphal growth, conidiation, and pathogenicity, and was more sensitive to hyperosmotic stress and oxidative stress. Moreover, ∆Moade8 caused decreased activity of MoTor kinase due to blocked purine nucleotide synthesis. The autophagy level was also impaired in ∆Moade8. Additionally, MoAde5, 7, 6, and 12, which are involved in de novo purine nucleotide biosynthesis, were also analyzed, and the mutants showed defects similar to the defects of ∆Moade8. In summary, de novo purine nucleotide biosynthesis is essential for conidiation, development, and pathogenicity in M. oryzae.

12.
Front Med (Lausanne) ; 9: 960847, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059832

RESUMO

Background: Early recognition of patients with community-acquired pneumonia (CAP) at risk of poor outcomes is crucial. However, there is no effective assessment tool for predicting the development of respiratory failure in patients with CAP. Diaphragmatic ultrasonography (DUS) is a novel technique developed for evaluating diaphragmatic function via measurements of the diaphragm thickening fraction (DTF) and diaphragm excursion (DE). This study evaluated the accuracy of DUS in predicting the development of respiratory failure in patients with CAP, as well as the feasibility of its use in the emergency department (ED) setting. Materials and methods: This was a single-center prospective cohort study. We invited all patients with ED aged ≥ 20 years who were diagnosed with CAP of pneumonia severity index (PSI) SIe diagnosed with CAP of pneumonia severe with respiratory failure or septic shock were excluded. Two emergency physicians performed DUS to obtain DTF and DE measurements. Data were collected to calculate PSI, CURB-65 score, and Infectious Diseases Society of America/American Thoracic Society severity criteria. Study endpoints were taken at the development of respiratory failure or 30 days post-ED presentation. Continuous variables were analyzed using T-tests, while categorical variables were analyzed using chi-square tests. Further logistic regression and receiver operating characteristic curve analyses were performed to examine the ability to predict the development of respiratory failure. Intra- and inter-rater reliability was examined with intraclass correlation coefficients (ICCs). Results: In this study, 13 of 50 patients with CAP enrolled developed respiratory failure. DTF was found to be an independent predictor (OR: 0.939, p = 0.0416). At the optimal cut-off point of 23.95%, DTF had 69.23% of sensitivity, 83.78% of specificity, 88.57% of negative predictive value, and 80% of accuracy. Intra- and inter-rater analysis demonstrated good consistency (intra-rater ICC 0.817, 0.789; inter-rater ICC 0.774, 0.781). Conclusion: DUS assessment of DTF may reliably predict the development of respiratory failure in patients with CAP presenting to the ED. Patients with DTF > 23.95% may be considered for outpatient management.

13.
Research (Wash D C) ; 2022: 9873203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082209

RESUMO

Hygroelectricity generators (HEGs) utilize the latent heat stored in environmental moisture for electricity generation, but nevertheless are showing relatively low power densities due to their weak energy harvesting capacities. Inspired by epiphytes that absorb ambient moisture and concurrently capture sunlight for dynamic photosynthesis, we propose herein a scenario of all-biobased hydrovoltaic-photovoltaic electricity generators (HPEGs) that integrate photosystem II (PSII) with Geobacter sulfurreducens (G.s) for simultaneous energy harvesting from both moisture and sunlight. This proof of concept illustrates that the all-biobased HPEG generates steady hygroelectricity induced by moisture absorption and meanwhile creates a photovoltaic electric field which further strengthens electricity generation under sunlight. Under environmental conditions, the synergic hydrovoltaic-photovoltaic effect in HPEGs has resulted in a continuous output power with a high density of 1.24 W/m2, surpassing all HEGs reported hitherto. This work thus provides a feasible strategy for boosting electricity generation via simultaneous energy harvesting from ambient moisture and sunlight.

14.
Phys Rev Lett ; 129(6): 063902, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-36018645

RESUMO

High-order topological phases, such as those with nontrivial quadrupole moments [1,2], protect edge states that are themselves topological insulators in lower dimensions. So far, most quadrupole phases of light are explored in linear optical systems, which are protected by spatial symmetries [3] or synthetic symmetries [1,2,4-7]. Here we present Floquet quadrupole phases in driven nonlinear photonic crystals that are protected by space-time screw symmetries [8]. We start by illustrating space-time symmetries by tracking the trajectory of instantaneous optical axes of the driven media. Our Floquet quadrupole phase is then confirmed in two independent ways: symmetry indices at high-symmetry momentum points and calculations of the nested Wannier bands. Our Letter presents a general framework to analyze symmetries in driven optical materials and paves the way to further exploring symmetry-protected topological phases in Floquet systems and their optoelectronic applications.

15.
Pharmaceutics ; 14(8)2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36015267

RESUMO

Chemotherapy has an essential role not only in advanced solid tumor therapy intervention but also in society's health at large. Chemoresistance, however, seriously restricts the efficiency and sensitivity of chemotherapeutic agents, representing a significant threat to patients' quality of life and life expectancy. How to reverse chemoresistance, improve efficacy sensitization response, and reduce adverse side effects need to be tackled urgently. Recently, studies on the effect of ultrasonic microbubble cavitation on enhanced tissue permeability and retention (EPR) have attracted the attention of researchers. Compared with the traditional targeted drug delivery regimen, the microbubble cavitation effect, which can be used to enhance the EPR effect, has the advantages of less trauma, low cost, and good sensitization effect, and has significant application prospects. This article reviews the research progress of ultrasound-mediated microbubble cavitation in the treatment of solid tumors and discusses its mechanism of action to provide new ideas for better treatment strategies.

16.
Plants (Basel) ; 11(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36015451

RESUMO

Recent technological advances allow us to resolve molecular processes in living cells with high spatial and temporal resolution. Based on these technological advances, membraneless intracellular condensates formed by reversible functional aggregation and phase separation have been identified as important regulatory modules in diverse biological processes. Here, we present bioinformatic and cellular studies highlighting the possibility of the involvement of the central activator of ethylene responses EIN2 in such cellular condensates and phase separation processes. Our work provides insight into the molecular type (identity) of the observed EIN2 condensates and on potential intrinsic elements and sequence motifs in EIN2-C that may regulate condensate formation and dynamics.

17.
Appl Bionics Biomech ; 2022: 4658709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032048

RESUMO

Methods: A retrospective study was conducted on the clinical records of 148 children diagnosed with severe beta thalassemia who were admitted to our hospital between October 2018 and September 2021. The patients were separated into two groups, a control group and an intervention group, with 74 cases in each group, according to the various care approaches. The basic treatment regimen was given to all of the children: deferoxamine mesylate combined with deferiprone. During treatment, the control group received routine care, and the intervention group adopted the FCC model based on a mobile app. The quality of life scale for children and adolescents (QLSCA) score, the family assessment device (FAD) score, the exercise of self-care agency scale (ESCA) score, and the medication compliance scale score were compared between the two groups. Results: The QLSCA score, ESCA score, and medication compliance scale score of the intervention group were significantly higher than those of the control group and showed a significant difference (intergroup effect: F = 198.400, 259.200, and 129.800, all P < 0.001). Scores in both groups increased over time (time effect: F = 19.350, 40.830, and 12.130, all P < 0.001), and there was an interaction effect between grouping and time (interaction effect: F = 3.937, 12.020, and 5.028). The P values were 0.020, <0.001, and 0.007. The FAD score of the intervention group was significantly lower than that of the control group (intergroup effect: F = 177.200, P < 0.001). The FAD scores of both groups decreased over time (time effect: F = 7.921, P = 0.005). There was an interaction effect between groups and time (interaction effect: F = 5.206, P = 0.006). Conclusion: The application effect of the mobile app-based FCC model combined with the comprehensive iron removal treatment program in children with severe beta thalassemia is significant, which can significantly improve the quality of life, family function, self-care ability, and medication compliance of children, and has high clinical application value.

18.
RSC Adv ; 12(34): 22295-22301, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-36043060

RESUMO

Five previously undescribed epoxy octa-hydronaphthalene polyketides, altereporenes A-E (1-5) were isolated from rice culture of the endophytic fungus Alternaria sp. YUD20002 derived from the tubers of Solanum tuberosum. Their structures were determined on the basis of comprehensive spectroscopic analyses, while the absolute configurations were elucidated by the comparison of experimental and calculated specific rotations. Meanwhile, the antimicrobial, cytotoxic, anti-inflammatory and acetylcholinesterase inhibitory activities of compounds 1-5 were also investigated.

19.
J Agric Food Chem ; 70(34): 10563-10570, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35993186

RESUMO

Sclareol glycol is a key starting material with significant market interest for synthesizing high-value ambroxide, a sustainable substitute for ambergris in high-end fragrances. Sclareol glycol can be obtained by biotransformation of sclareol, a labdane-type diterpene, using Hyphozyma roseonigra. However, the pathway and mechanism of sclareol glycol biosynthesis remain unclear. In this study, the dynamic time course of sclareol biotransformation was explored by resting cell assays and several intermediates produced during biotransformation were detected. The results show that (1) sclareol glycol and sclareolide are not interconverted and are potentially synthesized via different metabolic pathways and (2) several putative intermediates resulting from biotransformation are featured with a labdane carbon backbone, including isomerized and oxidized analogues. A plausible transformation pathway of sclareol in H. roseonigra was proposed based on detected metabolites. This study sheds light on the biosynthetic mechanism of sclareol glycol and paves a way for the future biotechnological production of this promising compound.


Assuntos
Ascomicetos , Diterpenos , Ascomicetos/metabolismo , Biotransformação , Carbono/metabolismo , Diterpenos/metabolismo
20.
J Agric Food Chem ; 70(33): 10296-10304, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35947430

RESUMO

Premature yeast flocculation (PYF) is one of the pivotal problems affecting beer flavor and production. PYF is induced by certain non-starch polysaccharides produced by the degradation of malted barley husks upon the growth of contaminated microorganisms, such as Fusarium graminearum. In this research, the formation mechanism of PYF was uncovered by investigating the secretome of F. graminearum MH1 inoculated to the barley husk. The polysaccharide extract of degraded husk was ultrafiltrated into four fractions and characterized by the minimum PYF concentration, molecular mass distribution, monosaccharide composition, and zeta potential. Among the four fractions, the high-molecular-weight polysaccharide fraction had the highest content of uronic acid and the most negative zeta potential, which contributed to the most severe PYF phenomenon. In addition, the PYF yeast showed a more negative zeta potential than the control yeast during the small-scale brewing process. This is aligned to the negatively charged polysaccharides potentially bonded to the surface of yeast cells through the calcium cation in the same fermentation system, which results in rapid flocculation and precipitation. Approximately 12% of the 214 proteins identified in the Fusarium graminearum MH1 secretome were hemicellulases, which substantially interpreted the mechanism of polysaccharides inducing PYF yeast during beer brewing.


Assuntos
Fusarium , Hordeum , Floculação , Fusarium/metabolismo , Hordeum/metabolismo , Doenças das Plantas , Saccharomyces cerevisiae
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