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The degradability of the biocomposite produced from a binary mixture of thermoplastic banana starch (TPS) and polycaprolactone (PCL) reinforced with fique fibers (Fs) was evaluated in three different environments (soil, compost, water). An experimental design with two factors (soil and compost) and three levels (5, 10, and 20 cm) was used, with additional tests for a third aqueous environment (water from the lake of the Universidad del Valle) at a depth of 20 cm. The biocomposite was prepared from the implementation of a twin-screw extrusion process of the binary mixture TPS/PCL and fique fibers (54, 36, and 10% composition, respectively), followed by hot compression molding, and after that, generating ASTM D638 type V specimens using a stainless-steel die. The specimens were dried and buried according to the experimental design, for a total experimental time of 90 days, and removing samples every 30 days. After 90 days, all samples showed signs of degradation, where the best results were obtained in the compost at a depth of 20 cm (34 ± 4% mass loss and a decrease in tensile strength of 77.3%, which indicates that the material lost mechanical properties). TPS was the fastest disappearing component and promoted the degradation of the composite material as it disappeared. Finally, the aqueous media presented the lowest degradation results, losing only 20% of its initial mass after 90 days of the experiment, being the least effective environment in which the biocomposite can end up.

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SUMMARY: The study and teaching of human anatomy is one of the cornerstones of education of basis science in health professionals. The aim of this study was to present a bibliometric analysis of the global outputs of research on the teaching and learning of human anatomy in the last two decades. The Scopus database was used to search and retrieve studies related to this topic between 2001 and February 10, 2021. A total of 10,481 documents were found through a systematic search strategy. A growing trend in publishing research results was evidenced, starting in 2001 with a considerable increase between 2012 and 2015. Four clusters were identified in studies related to teaching-learning methodologies of human anatomy. These clusters correspond to traditional methods and emerging methodologies such as the use of information and communication technologies, 3D impressions and diagnostic images. In addition, the results of this study indicate that the United States, the United Kingdom and Germany were the countries with the highest production in the number of publications on this topic. Although new methodologies have been included in teaching and learning human anatomy, such as the use of information and communication technologies, the trend in these processes continues to be mediated by the traditional method of cadaveric dissection. However, there is an increase in the immersion of virtual resources as part of these methodologies that should be integrated.

RESUMEN: La enseñanza y el aprendizaje de la anatomía humana es uno de los pilares de la educación científica básica para los profesionales de la salud. El objetivo de este estudio fue presentar un análisis bibliométrico de los resultados globales de la investigación sobre la enseñanza y el aprendizaje de la anatomía humana en las últimas dos décadas. Se utilizó la base de datos Scopus para buscar y recuperar estudios relacionados con este tema entre 2001 y el 10 de febrero de 2021. Se encontraron un total de 10.481 documentos mediante una estrategia de búsqueda sistemática. Hubo una tendencia creciente en la publicación de resultados de investigación, comenzando en 2001 con un aumento considerable entre 2012 y 2015. Se identificaron cuatro grupos en estudios relacionados con metodologías de enseñanza-aprendizaje de anatomía humana. Estos clusters corresponden a métodos tradicionales, metodologías emergentes como el uso de tecnologías de información y comunicación, impresión 3D e imágenes de diagnósticas. Además, los resultados de este estudio indican que Estados Unidos, Reino Unido y Alemania fueron los países con mayor producción en el número de publicaciones sobre este tema. Si bien se han incluido nuevas metodologías en la enseñanza y el aprendizaje de la anatomía humana, como el uso de tecnologías de la información y la comunicación, la tendencia en estos procesos continúa siendo a través del método tradicional y la disección cadavérica. Sin embargo, hay un incremento en la inclusión de recursos virtuales que se integran al aula.

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Streptomyces clavuligerus (S. clavuligerus) has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of ß-lactamase enzymes. In this study, S. clavuligerus cultivated in 2D rocking bioreactor in fed-batch operation produced CA at comparable rates to those observed in stirred tank bioreactors. A reduced model of S. clavuligerus metabolism was constructed by using a bottom-up approach and validated using experimental data. The reduced model was implemented for in silico studies of the metabolic scenarios arisen during the cultivations. Constraint-based analysis confirmed the interrelations between succinate, oxaloacetate, malate, pyruvate, and acetate accumulations at high CA synthesis rates in submerged cultures of S. clavuligerus. Further analysis using shadow prices provided a first view of the metabolites positive and negatively associated with the scenarios of low and high CA production.

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Considering that cancer continues to be an important cause of death worldwide, several conventional anticancer treatments are widely used. However, most of them display low selectivity against malignant cells and induce many adverse side effects. Among these, the use of therapies based on 5-Fluorouracil (5-FU) has been one of the most efficient, with a broad-spectrum. Due to these circumstances, various modifications of 5-FU have been developed to improve drug delivery and reduce side effects. Among the optimization strategies, modifications of 5-FU at N1 or N3 position are made, usually including the incorporation of pharmacologically active compounds with anticancer activity (called hybrid molecule) and functionalization with other groups of compounds (called conjugates). Several studies have been conducted in the search for new alternative therapies against cancer. Many of them have evidenced that hybrid compounds exhibit good anticancer activity, which has emerged as a promising strategy in this field of drug discovery and development. Furthermore, the binding of 5-FU to amino acids, peptides, phospholipids, polymers, among others, improves metabolic stability and absorption. This review highlights the potential of hybrids and derivatives based on 5-FU as a scaffold for the development of antitumor agents. Besides, it also presents a detailed description of the different strategies employed to design and synthesized these compounds, together with their biological activities and structure-activity relationship (SAR) analysis.

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Clavulanic acid (CA) is an irreversible ß-lactamase enzyme inhibitor with a weak antibacterial activity produced by Streptomyces clavuligerus (S. clavuligerus). CA is typically co-formulated with broad-spectrum ß­lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria that possess ß­lactam resistance. The clinical importance of CA and the complexity of the production process motivate improvements from an interdisciplinary standpoint by integrating metabolic engineering strategies and knowledge on metabolic and regulatory events through systems biology and multi-omics approaches. In the large-scale bioprocessing, optimization of culture conditions, bioreactor design, agitation regime, as well as advances in CA separation and purification are required to improve the cost structure associated to CA production. This review presents the recent insights in CA production by S. clavuligerus, emphasizing on systems biology approaches, strain engineering, and downstream processing.

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All reaction steps during the biosynthesis of suicidal clavulanic acid (coformulated with ß-lactam antibiotics and used to fight bacterial infections) are known, except for the crucial 3S,5S → 3R,5R double epimerization needed to produce a biologically active stereoisomer, for which mechanistic hypothesis is subject to debate. In this work, we provide evidence for a reaction channel for the double inversion of configuration that involves a total of six reaction steps. When mediated by an enzyme with a terminal S-H bond, this highly complex reaction is spontaneous in the absence of solvents. Polarizable continuum models introduce reaction barriers in aqueous environments because of the strong destabilization of the first transition state. Molecular geometries and electronic structures in both cases indicate that solvent-free spontaneity and aqueous medium barriers are both firmly rooted in a substantial reorganization of the electron density right at the onset of the reaction, mostly involving a cyclic evolution/involution of large regions of π delocalization used to stabilize the excess charge left after the initial proton abstraction.

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Streptomyces clavuligerus is a filamentous Gram-positive bacterial producer of the ß-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the Streptomyces genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of Streptomyces clavuligerus was reconstructed and used to study the experimentally observed effect of oxygen and phosphate concentrations on clavulanic acid biosynthesis under high and low shear stress. A flux balance analysis based on experimental evidence revealed that clavulanic acid biosynthetic reaction fluxes are favored in conditions of phosphate limitation, and this is correlated with enhanced activity of central and amino acid metabolism, as well as with enhanced oxygen uptake. In silico and experimental results show a possible slowing down of tricarboxylic acid (TCA) due to reduced oxygen availability in low shear stress conditions. In contrast, high shear stress conditions are connected with high intracellular oxygen availability favoring TCA activity, precursors availability and clavulanic acid (CA) production.

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Streptomyces clavuligerus is a gram-positive filamentous bacterium notable for producing clavulanic acid (CA), an inhibitor of ß-lactamase enzymes, which confers resistance to bacteria against several antibiotics. Here we present a comparative analysis of the morphological and metabolic response of S. clavuligerus linked to the CA production under low and high shear stress conditions in a 2D rocking-motion single-use bioreactor (CELL-tainer ®) and stirred tank bioreactor (STR), respectively. The CELL-tainer® guarantees high turbulence and enhanced volumetric mass transfer at low shear stress, which (in contrast to bubble columns) allows the investigation of the impact of shear stress without oxygen limitation. The results indicate that high shear forces do not compromise the viability of S. clavuligerus cells; even higher specific growth rate, biomass, and specific CA production rate were observed in the STR. Under low shear forces in the CELL-tainer® the mycelial diameter increased considerably (average diameter 2.27 in CELL-tainer® vs. 1.44 µm in STR). This suggests that CA production may be affected by a lower surface-to-volume ratio which would lead to lower diffusion and transport of nutrients, oxygen, and product. The present study shows that there is a strong correlation between macromorphology and CA production, which should be an important aspect to consider in industrial production of CA.

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Clavulanic acid (CA) is a ß-lactam antibiotic with a strong inhibitory effect on ß-lactamase enzymes. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus (S. clavuligerus). CA is an unstable molecule in aqueous solution and its stability depends strongly on temperature and concentration. In this contribution, the experimental data of CA stability, produced in chemically defined media and exposed to temperatures between -80 and 25 °C, are presented. The chromophore clavulanate-imidazole (CAI) is commonly used for analysis and quantification of CA samples by High Performance Liquid Chromatography (HPLC); nevertheless, this molecule is also susceptible to suffer degradation in aqueous solution, potentially affecting the quantification of CA. Data of CAI concentration for samples conserved at 4 °C and 25 °C are also presented. A reversible-irreversible kinetic model was applied to estimate the degradation rate of CA. Data from numerical simulations of CA degradation using the proposed kinetic model are also graphically presented. The data show the clavulanic acid instability in fermentation broths, in a range of temperatures of interest for bioprocess operation, downstream processing, samples quantification, conservation and storage.