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Materials with a soft tissue regenerative capacity can be produced using biopolymer scaffolds and nanomaterials, which allow injured tissue to recover without any side effects or limitations. Four formulations were prepared using polyvinyl alcohol (PVA) and chitosan (CS), with silicon dioxide nanoparticles (NPs-SiO 2 ) incorporated using the freeze-drying method at a temperature of -50 °C. TGA and DSC showed no change in thermal degradation, with glass transition temperatures around 74 °C and 77 °C. The interactions between the hydroxyl groups of PVA and CS remained stable. Scanning electron microscopy (SEM) indicated that the incorporation of NPs-SiO 2 complemented the freeze-drying process, enabling the dispersion of the components on the polymeric matrix and obtaining structures with a small pore size (between 30 and 60 μm) and large pores (between 100 and 160 μm). The antimicrobial capacity analysis of Gram-positive and Gram-negative bacteria revealed that the scaffolds inhibited around 99% of K. pneumoniae , E. cloacae , and S. aureus ATCC 55804. The subdermal implantation analysis demonstrated tissue growth and proliferation, with good biocompatibility, promoting the healing process for tissue restoration through the simultaneous degradation and formation of type I collagen fibers. All the results presented expand the boundaries in tissue engineering and regenerative medicine by highlighting the crucial role of nanoparticles in optimizing scaffold properties.

Bone tissue engineering is a promising alternative to repair wounds caused by cellular or physical accidents that humans face daily. In this sense, the search for new graphene oxide (GO) nanofillers related to their degree of oxidation is born as an alternative bioactive component in forming new scaffolds. In the present study, three different GOs were synthesized with varying degrees of oxidation and studied chemically and tissue-wise. The oxidation degree was determined through infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS), and Raman spectroscopy (RS). The morphology of the samples was analyzed using scanning electron microscopy (SEM). The oxygen content was deeply described using the deconvolution of RS and XPS techniques. The latter represents the oxidation degree for each of the samples and the formation of new bonds promoted by the graphitization of the material. In the RS, two characteristic bands were observed according to the degree of oxidation and the degree of graphitization of the material represented in bands D and G with different relative intensities, suggesting that the samples have different crystallite sizes. This size was described using the Tuinstra-Koenig model, ranging between 18.7 and 25.1 nm. Finally, the bone neoformation observed in the cranial defects of critical size indicates that the F1 and F2 samples, besides being compatible and resorbable, acted as a bridge for bone healing through regeneration. This promoted healing by restoring bone and tissue structure without triggering a strong immune response.

Sphaerellopsis species are putative hyperparasites of rust fungi and may be promising biological control agents (BCA) of rust diseases. However, few detailed studies limit potential BCA development in Sphaerellopsis. Here, we explored the biogeography, host-specificity, and species diversity of Sphaerellopsis and examined the early infection stage of one species, S. macroconidialis, to infer its trophic status. We randomly screened 5,621 rust specimens spanning 99 genera at the Arthur Fungarium for the presence of Sphaerellopsis. We identified 199 rust specimens infected with Sphaerellopsis species on which we conducted morphological and multi-locus phylogenetic analyses. Five Sphaerellopsis species were recovered, infecting a total of 122 rust species in 18 genera from 34 countries. Sphaerellopsis melampsorinearum sp. nov. is described as a new species based on molecular phylogenetic data and morphological features of the sexual and asexual morphs. Sphaerellopsis paraphysata was the most commonly encountered species, found on 77 rust specimens, followed by Sphaerellopsis macroconidialis on 56 and S. melampsorinearum on 55 examined specimens. The type species, Sphaerellopsis filum, was found on 12 rust specimens and Sphaerellopsis hakeae on a single specimen. We also recovered and documented for the first time, the sexual morph of S. macroconidialis, from a specimen collected in Brazil. Our data indicate that Sphaerellopsis species are not host specific and furthermore that most species are cosmopolitan in distribution. However, S. paraphysata is more abundant in the tropics, and S. hakeae may be restricted to Australia. Finally, we confirm the mycoparasitic strategy of S. macroconidialis through in-vitro interaction tests with the urediniospores of Puccinia polysora. Shortly after germination, hyphae of S. macroconidialis began growing along the germ tubes of P. polysora and coiling around them. After 12 days of co-cultivation, turgor loss was evident in the germ tubes of P. polysora, and appressorium-like structures had formed on urediniospores. The interaction studies indicate that Sphaerellopsis species may be more effective as a BCA during the initial stages of rust establishment., (© 2024. The Author(s).)

Electrospun nanocomposite scaffolds with improved bioactive and biological properties were fabricated from a blend of polycaprolactone (PCL) and starch, and then combined with 5 wt% of calcium oxide (CaO) nanoparticles sourced from eggshells. SEM analyses showed scaffolds with fibrillar morphology and a three-dimensional structure. The hydrophilicity of scaffolds was improved with starch and CaO nanoparticles, which was evidenced by enhanced water absorption (3500 %) for 7 days. In addition, PCL/Starch/CaO scaffolds exhibited major degradation, with a mass loss of approximately 60 % compared to PCL/Starch and PCL/CaO. The PCL/Starch/CaO scaffolds decreased in crystallinity as intermolecular interactions between the nanoparticles retarded the mobility of the polymeric chains, leading to a significant increase in Young's modulus (ca. 60 %) and a decrease in tensile strength and elongation at break, compared to neat PCL. SEM-EDS, FT-IR, and XRD analyses indicated that PCL/Starch/CaO scaffolds presented a higher biomineralization capacity due to the ability to form hydroxyapatite (HA) in their surface after 28 days. The PCL/Starch/CaO scaffolds showed attractive biological performance, allowing cell adhesion and viability of M3T3-E1 preosteoblastic cells. In vivo analysis using a subdermal dorsal model in Wistar rats showed superior biocompatibility and improved resorption process compared to a pure PCL matrix. This biological analysis suggested that the PCL/Starch/CaO electrospun mats are suitable scaffolds for guiding the regeneration of bone tissue., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rust fungi (Pucciniales) are plant pathogens that can cause devastating yield losses to economically important crops and threaten native plants with extinction. Rusts are usually controlled with fungicides when rust-resistant plant varieties are unavailable. However, natural enemies may offer an alternative to chemicals by acting as biological controls. The larvae of Mycodiplosis Rübsaamen (49 spp.) feed on the spores of rusts and powdery mildew fungi and have been suggested as a potential biocontrol candidate for disease-causing rusts. However, little is known about the phylogenetic relationships, biogeography, and host range of this genus. We screened 5,665 rust specimens from fungarium specimens and field collections and recovered a total of 363 larvae on 315 rust specimens from 17 countries. Three mitochondrial and 2 nuclear loci were amplified and sequenced for the phylogenetic reconstruction of 129 individuals. We recovered 12 clades, of which 12 and 10 were supported with maximum likelihood and Bayesian inference, respectively. Of the 12 clades, 7 comprised species from multiple continents and climatic regions, and 5 comprised species from a single region. Individuals forming clades were collected from 2 to 18 rust species, suggesting that Mycodiplosis species have a broad host range. In total, Mycodiplosis larvae were identified on 44 different rust species collected from 18 plant families. Future studies should focus on expanding field sampling efforts, including data from additional gene regions, and incorporating morphological data to further elucidate species diversity and distribution patterns., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

Hybrid scaffolds that are based on PLA and PLA/PMMA with 75/25, 50/50, and 25/75 weight ratios and functionalized with 10 wt.% of bioglass nanoparticles (n-BG) were developed using an electrospinning technique with a chloroform/dimethylformamide mixture in a 9:1 ratio for bone tissue engineering applications. Neat PLA and PLA/PMMA hybrid scaffolds were developed successfully through a (CF/DMF) solvent system, obtaining a random fiber deposition that generated a porous structure with pore interconnectivity. However, with the solvent system used, it was not possible to generate fibers in the case of the neat PMMA sample. With the increase in the amount of PMMA in PLA/PMMA ratios, the fiber diameter of hybrid scaffolds decreases, and the defects (beads) in the fiber structure increase; these beads are associated with a nanoparticle agglomeration, that could be related to a low interaction between n-BG and the polymer matrix. The Young's modulus of PLA/PMMA/n-BG decreases by 34 and 80%, indicating more flexible behavior compared to neat PLA. The PLA/PMMA/n-BG scaffolds showed a bioactive property related to the presence of hydroxyapatite crystals in the fiber surface after 28 days of immersion in a Simulated Body Fluids solution (SBF). In addition, the hydrolytic degradation process of PLA/PMMA/n-BG, analyzed after 35 days of immersion in a phosphate-buffered saline solution (PBS), was less than that of the pure PLA. The in vitro analysis using an HBOF-1.19 cell line indicated that the PLA/PMMA/n-BG scaffold showed good cell viability and was able to promote cell proliferation after 7 days. On the other hand, the in vivo biocompatibility evaluated via a subdermal model in BALC male mice corroborated the good behavior of the scaffolds in avoiding the generation of a cytotoxic effect and being able to enhance the healing process, suggesting that the materials are suitable for potential applications in tissue engineering.

The constant demand for biocompatible and non-invasive materials for regenerative medicine in accidents and various diseases has driven the development of innovative biomaterials that promote biomedical applications. In this context, using sol-gel and ionotropic gelation methods, zinc oxide nanoparticles (NPs-ZnO) and chitosan nanoparticles (NPs-CS) were synthesized with sizes of 20.0 nm and 11.98 nm, respectively. These nanoparticles were incorporated into chitosan scaffolds through the freeze-drying method, generating a porous morphology with small (<100 μm), medium (100-200 μm), and large (200-450 μm) pore sizes. Moreover, the four formulations showed preliminary bioactivity after hydrolytic degradation, facilitating the formation of a hydroxyapatite (HA) layer on the scaffold surface, as evidenced by the presence of Ca (4%) and P (5.1%) during hydrolytic degradation. The scaffolds exhibited average antibacterial activity of F1 = 92.93%, F2 = 99.90%, F3 = 74.10%, and F4 = 88.72% against four bacterial strains: K. pneumoniae , E. cloacae , S. enterica , and S. aureus . In vivo , evaluation confirmed the biocompatibility of the functionalized scaffolds, where F2 showed accelerated resorption attributed to the NPs-ZnO. At the same time, F3 exhibited controlled degradation with NPs-CS acting as initiation points for degradation. On the other hand, F4 combined NPs-CS and NPs-ZnO, resulting in progressive degradation, reduced inflammation, and an organized extracellular matrix. All the results presented expand the boundaries in tissue engineering and regenerative medicine by highlighting the crucial role of nanoparticles in optimizing scaffold properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Polymer-based nanocomposites such as polycaprolactone/graphene oxide (PCL/GO) have emerged as alternatives for bone tissue engineering (BTE) applications. The objective of this research was to investigate the impact of a gelatin (Gt) coating on the degradability and different properties of PCL nanofibrous scaffolds fabricated by an electrospinning technique with 1 and 2 wt% GO. Uniform PCL/GO fibers were obtained with a beadless structure and rough surface. PCL/GO scaffolds exhibited an increase in their crystallization temperature (Tc), attributed to GO, which acted as a nucleation agent. Young's modulus increased by 32 and 63% for the incorporation of 1 and 2 wt% GO, respectively, in comparison with neat PCL. A homogeneous Gt coating was further applied to these fibers, with incorporations as high as 24.7 wt%. The introduction of the Gt coating improved the hydrophilicity and degradability of the scaffolds. Bioactivity analysis revealed that the hydroxyapatite crystals were deposited on the Gt-coated scaffolds, which made them different from their uncoated counterparts. Our results showed the synergic effect of Gt and GO in enhancing the multifunctionality of the PCL, in particular the degradability rate, bioactivity, and cell adhesion and proliferation of hGMSC cells, making it an interesting biomaterial for BTE.

Tissue accidents provide numerous pathways for pathogens to invade and flourish, causing additional harm to the host tissue while impeding its natural healing and regeneration. Essential oils (EOs) exhibit rapid and effective antimicrobial properties without promoting bacterial resistance. Clove oils (CEO) demonstrate robust antimicrobial activity against different pathogens. Chitosan (CS) is a natural, partially deacetylated polyamine widely recognized for its vast antimicrobial capacity. In this study, we present the synthesis of four membrane formulations utilizing CS, polyvinyl alcohol (PVA), and glycerol (Gly) incorporated with CEO and nanobioglass (n-BGs) for applications in subdermal tissue regeneration. Our analysis of the membranes' thermal stability and chemical composition provided strong evidence for successfully blending polymers with the entrapment of the essential oil. The incorporation of the CEO in the composite was evidenced by the increase in the intensity of the band of C-O-C in the FTIR; furthermore, the increase in diffraction peaks, as well as the broadening, provide evidence that the introduction of CEO perturbed the crystal structure. The morphological examination conducted using scanning electron microscopy (SEM) revealed that the incorporation of CEO resulted in smooth surfaces, in contrast to the porous morphologies observed with the n-BGs. A histological examination of the implanted membranes demonstrated their biocompatibility and biodegradability, particularly after a 60-day implantation period. The degradation process of more extensive membranes involved connective tissue composed of type III collagen fibers, blood vessels, and inflammatory cells, which supported the reabsorption of the composite membranes, evidencing the material's biocompatibility.

Calcium oxide nanoparticles (n-CaO) ca. 22 nm were obtained from eggshell waste. The n-CaO was incorporated into the PLA matrix in 10 and 20 wt% of filler content by electrospinning process to get PLA/n-CaO fibers with homogenous morphology and diameter as a potential use in scaffold for bone tissue regeneration. The incorporation of n-CaO into PLA modifies the mechanical properties, having a reinforcement effect on the matrix. The Young modulus for PLA/n-CaO nanocomposites increased between 122 and 138 % concerning neat PLA fibers, showing a more rigid behavior. The PLA/n-CaO nanocomposite fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after seven days in SBF solution. The biocidal and biological properties of PLA/n-Cao with 20 wt% showed a 30 % reduction in bacterial viability against S. aureus and 11 % against E. coli after 6 h of bacterial exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, allowing cell adhesion and proliferation in the RPMI medium. The PLA/n-CaO with 20 wt% of nanoparticles showed a higher capacity to promote osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after seven days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of the prepared scaffolds; the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material, improving the healing process. These results validated using n-CaO to enhance the functionality of polymer matrices as a PLA, bringing bioactive, biocide, and biocompatible properties, opening a new and interesting route to develop new biomaterials as a scaffold for bone tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Limonium sinuatum (Plumbaginaceae) is the most commonly cultivated recognizable cut flower crop in the genus Limonium. It is known by several common names including statice and sea lavender, due to its lilac-colored flowers and the fact that it naturally inhabits mainly coastal areas (Mellesse et al, 2013). Limonium sinuatum is native to the Mediterranean, although as a popular garden plant, has been naturalized in other parts of the world including coastal areas of California (USDA NRCS 2020). Cultivated L. sinuatum is used in fresh and dry flower arrangements in the Americas, comprising approximately 20% of the floriculture cultivated area in Ecuador (Vega and Morales 2011; Abascal Cañas 2017). In December 2014, L. sinuatum plants in the public park "Baños del Inca" in Cajamarca, Peru (S 7 9'46"; W 78 27'53"), were found infected with a rust disease. The plants were scattered in the park but infection incidence was 100% as individual plants were all found to be infected (Fig 1). Based on the percentage of symptomatic areas, including the yellow halos around pustules, calculated with ImageJ (Collins, 2007) from field photographs, the disease severity was estimated to be 58.9% in average, ranging from 19.8% up to 90.0%. Uredinia were present on both sides of the leaves as well as on stems and were roundish, oblong, pulverulent, and cinnamon brown in color; urediniospores 25.5 to 35.0 × 22.5 to 31.0 µm, were globoid to ellipsoid; urediniospore walls were cinnamon-brown, 2.5 to 3.0 µm thick, densely verrucose, with 2 to 3 equatorial germ pores. Few telia were present on leaves; these were scattered roundish or oblong, and greyish in color; teliospores 26.5 to 41.0 × 16.0 to 25.0 µm, were ellipsoid to obovoid, mostly attenuated at the apex; teliospore walls were colorless, 2-3 µm thick at sides, and up to 10 µm thick at apex. Teliospores readily germinated in sori producing basidia and basidiospores (Fig. 2). The rust features and dimensions of rust spores are consistent with available descriptions of Uromyces savulescui Rayss (Guyot 1951; Vakalounakis and Malathrakis 1987). To confirm identity, a 576 bp region of the 28S subunit of the ribosomal DNA repeat was sequenced following previously published protocols and primers (Aime 2006, Aime et al. 2018). The resulting sequence (GenBank Accession No. OR291160) shared 99.83% (573/574 bp) identity with a sequence deposited as Uromyces limonii (DC.) Lev. (accession KY764194, BPI910295, Demers et al. unpublished) from L. sinuatum in Ethiopia. However, U. limonii produces orange uredinia, thin-walled yellow-orange urediniospores, teliospores with mostly light chestnut brown wall and infects different hosts (Savile and Conners 1951). It is likely that KY764194 represents a misannotated record of U. savulescui. While Koch's postulates can be a useful tool for establishing causality in certain infectious diseases, their use may be limited when it comes to rust diseases based on old herbarium specimens. In our case, due to the age of the specimen, which is almost nine years old, various other methods were employed to identify the pathogen. These methods included microscopic examination for morphological criteria of the urediniospores and teliospores, as well as molecular techniques like 28S rDNA sequencing. Rust disease on L. sinuatum has been previously reported in Ecuador but the causal agent was identified as a Puccinia sp. and reported that the rust was able to destroy entire plots in humid conditions (Vega and Morales 2011). Whether this report also represent U. savulescui is not certain, but given that the urediniospores of Puccinia species are generally 2-celled, it is unlikely. García-Hernández et al. (2008) reported U. limonii on Limonium spp. from Chile, and Coca (2020) also reported U. limonii on Limonium sp., from Bolivia. However, judging from the photomicrographs (Coca 2020), the rust in the latter report is definitely U. savulescui and not U. limonii. Uromyces savulescui has been previously reported from the Mediterranean region and the Canary Islands (Vakalounakis and Malathrakis 1987). To our knowledge there is no report of this rust in the Americas, excepting the probable misidentifications already listed herein. The specimen has been deposited in the Arthur Fungarium at Purdue University as PURN15037.

Starch is a biodegradable biopolymer, a sustainable material that can replace conventional petrochemical-based plastics. However, starch has some limitations, as it must be processed by heating and treated mechanically with a plasticizer to become thermoplastic starch (TPS). Different variables such as mixing speeds, amount, and kind of plasticizers play a vital role in preparing TPS by melting. Despite this, the properties of the TPS are not comparable with those of traditional plastics. To overcome this limitation, microcellulose or nanocellulose is added to TPS by melt mixing, including the extrusion and internal mixing process, which enables large-scale production. This review aims to compile several studies that evaluate the effect of plasticizers, as well as the relevance of incorporating different cellulosic fillers of different dimensions on the properties of TPS obtained by melt mixing. Potential applications of these materials in food packaging, biomedical applications, and other opportunities are also described., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The increasing demand for non-invasive biocompatible materials in biomedical applications, driven by accidents and diseases like cancer, has led to the development of sustainable biomaterials. Here, we report the synthesis of four block formulations using polycaprolactone (PCL), polylactic acid (PLA), and zinc oxide nanoparticles (ZnO-NPs) for subdermal tissue regeneration. Characterization by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) confirmed the composition of the composites. Additionally, the interaction of ZnO-NPs mainly occurred with the C=O groups of PCL occurring at 1724 cm -1 , which disappears for F4, as evidenced in the FT-IR analysis. Likewise, this interaction evidenced the decrease in the crystallinity of the composites as they act as crosslinking points between the polymer backbones, inducing gaps between them and weakening the strength of the intermolecular bonds. Thermogravimetric (TGA) and differential scanning calorimetry (DSC) analyses confirmed that the ZnO-NPs bind to the carbonyl groups of the polymer, acting as weak points in the polymer backbone from where the different fragmentations occur. Scanning electron microscopy (SEM) showed that the increase in ZnO-NPs facilitated a more compact surface due to the excellent dispersion and homogeneous accumulation between the polymeric chains, facilitating this morphology. The in vivo studies using the nanocomposites demonstrated the degradation/resorption of the blocks in a ZnO-NP-dependant mode. After degradation, collagen fibers (Type I), blood vessels, and inflammatory cells continue the resorption of the implanted material. The results reported here demonstrate the relevance and potential impact of the ZnO-NP-based scaffolds in soft tissue regeneration.

Mitochondrial toxicity is a significant concern in the drug discovery process, as compounds that disrupt the function of these organelles can lead to serious side effects, including liver injury and cardiotoxicity. Different in vitro assays exist to detect mitochondrial toxicity at varying mechanistic levels: disruption of the respiratory chain, disruption of the membrane potential, or general mitochondrial dysfunction. In parallel, whole cell imaging assays like Cell Painting provide a phenotypic overview of the cellular system upon treatment and enable the assessment of mitochondrial health from cell profiling features. In this study, we aim to establish machine learning models for the prediction of mitochondrial toxicity, making the best use of the available data. For this purpose, we first derived highly curated datasets of mitochondrial toxicity, including subsets for different mechanisms of action. Due to the limited amount of labeled data often associated with toxicological endpoints, we investigated the potential of using morphological features from a large Cell Painting screen to label additional compounds and enrich our dataset. Our results suggest that models incorporating morphological profiles perform better in predicting mitochondrial toxicity than those trained on chemical structures alone (up to +0.08 and +0.09 mean MCC in random and cluster cross-validation, respectively). Toxicity labels derived from Cell Painting images improved the predictions on an external test set up to +0.08 MCC. However, we also found that further research is needed to improve the reliability of Cell Painting image labeling. Overall, our study provides insights into the importance of considering different mechanisms of action when predicting a complex endpoint like mitochondrial disruption as well as into the challenges and opportunities of using Cell Painting data for toxicity prediction.

The development of scaffolding obtained by electrospinning is widely used in tissue engineering due to porous and fibrous structures that can mimic the extracellular matrix. In this study, poly (lactic-co-glycolic acid) (PLGA)/collagen fibers were fabricated by electrospinning method and then evaluated in the cell adhesion and viability of human cervical carcinoma HeLa and NIH-3T3 fibroblast for potential application in tissue regeneration. Additionally, collagen release was assessed in NIH-3T3 fibroblasts. The fibrillar morphology of PLGA/collagen fibers was verified by scanning electron microscopy. The fiber diameter decreased in the fibers (PLGA/collagen) up to 0.6 µm. FT-IR spectroscopy and thermal analysis confirmed that both the electrospinning process and the blend with PLGA give structural stability to collagen. Incorporating collagen in the PLGA matrix promotes an increase in the material's rigidity, showing an increase in the elastic modulus (38%) and tensile strength (70%) compared to pure PLGA. PLGA and PLGA/collagen fibers were found to provide a suitable environment for the adhesion and growth of HeLa and NIH-3T3 cell lines as well as stimulate collagen release. We conclude that these scaffolds could be very effective as biocompatible materials for extracellular matrix regeneration, suggesting their potential applications in tissue bioengineering.

Electrospun scaffolds based on poly(l-lactic acid) (PLLA) with bioglass (n-BG) and zinc oxide (n-ZnO), and mixture of both, were developed to design bifunctional biomaterials with enhanced bioactive and biocidal properties. The presence of n-BG increased the fiber diameter of the pure PLA from 1.5 ± 0.3 μm to 3.0 ± 0.8 μm for 20 wt%. ZnO and the mixed nanoparticles did not significantly affect the morphology. The mechanical properties decreased with the presence of nanoparticles. Scaffolds based on PLA/n-BG promoted hydroxyapatite (HA) formation in simulated body fluid (SBF) that was inhibited with the presence of ZnO. Notably, mixed particles produced bioactivity although at longer times. The incorporation of n-ZnO produced a biocidal capacity against S. aureus in the polymeric scaffold, reaching a viability reduction of 60 % after 6 h of exposure. When both types of nanoparticles were combined, the bacterial viability reduction was 30 %. Pure PLA scaffolds and the composites with n-BG showed good ST-2 bone marrow-derived cell line viability, scaffolds with n-BG (pure or mixture) presented lower viability. Results validated the use of both n-BG and n-ZnO fillers for the development of novel bifunctional PLA-based scaffolds with both bioactive and biocidal properties for bone tissue engineering applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The development of scaffolds for cell regeneration has increased because they must have adequate biocompatibility and mechanical properties to be applied in tissue engineering. In this sense, incorporating nanofillers or essential oils has allowed new architectures to promote cell proliferation and regeneration of new tissue. With this goal, we prepared four membranes based on polylactic acid (PLA), polycaprolactone (PCL), titanium dioxide nanoparticles (TiO 2 -NPs), and orange essential oil (OEO) by the drop-casting method. The preparation of TiO 2 -NPs followed the sol-gel process with spherical morphology and an average size of 13.39 nm ± 2.28 nm. The results show how the TiO 2 -NP properties predominate over the crystallization processes, reflected in the decreasing crystallinity percentage from 5.2% to 0.6% in the membranes. On the other hand, when OEO and TiO 2 -NPs are introduced into a membrane, they act synergistically due to the inclusion of highly conjugated thermostable molecules and the thermal properties of TiO 2 -NPs. Finally, incorporating OEO and TiO 2 -NPs promotes tissue regeneration due to the decrease in inflammatory infiltrate and the appearance of connective tissue. These results demonstrate the great potential for biomedical applications of the membranes prepared.

The search for new biocompatible materials that can replace invasive materials in biomedical applications has increased due to the great demand derived from accidents and diseases such as cancer in various tissues. In this sense, four formulations based on polycaprolactone (PCL) and polylactic acid (PLA) incorporated with zinc oxide nanoparticles (ZnO-NPs) and tea tree essential oil (TTEO) were prepared. The sol-gel method was used for zinc oxide nanoparticle synthesis with an average size of 11 ± 2 nm and spherical morphology. On the other hand, Fourier Transformed infrared spectroscopy (FTIR) showed characteristic functional groups for each composite component. The TTEO incorporation in the formulations was related to the increased intensity of the C-O-C band. The thermal properties of the materials show that the degradative properties of the ZnO-NPs decrease the thermal stability. The morphological study by scanning electron microscopy (SEM) showed that the presence of TTEO and ZnO-NPs act synergistically, obtaining smooth surfaces, whereas membranes with the presence of ZnO-NPs or TTEO only show porous morphologies. Histological implantation of the membranes showed biocompatibility and biodegradability after 60 days of implantation. This degradation occurs through the fragmentation of the larger particles with the presence of connective tissue constituted by type III collagen fibers, blood vessels, and inflammatory cells, where the process of resorption of the implanted material continues.

The use of biopolymers for tissue engineering has recently gained attention due to the need for safer and highly compatible materials. Starch is one of the most used biopolymers for membrane preparation. However, incorporating other polymers into starch membranes introduces improvements, such as better thermal and mechanical resistance and increased water affinity, as we reported in our previous work. There are few reports in the literature on the biocompatibility of starch/chicken gelatin composites. We assessed the in vivo biocompatibility of the five composites (T1-T5) cassava starch/gelatin membranes with subdermal implantations in biomodels at 30, 60, and 90 days. The FT-IR spectroscopy analysis demonstrated the main functional groups for starch and chicken gelatin. At the same time, the thermal study exhibited an increase in thermal resistance for T3 and T4, with a remaining mass (~15 wt.%) at 800 °C. The microstructure analysis for the T2-T4 demonstrated evident roughness changes with porosity presence due to starch and gelatin mixture. The decrease in the starch content in the composites also decreased the gelatinization heats for T3 and T4 (195.67, 196.40 J/g, respectively). Finally, the implantation results demonstrated that the formulations exhibited differences in the degradation and resorption capacities according to the starch content, which is easily degraded by amylases. However, the histological results showed that the samples demonstrated almost complete reabsorption without a severe immune response, indicating a high in vivo biocompatibility. These results show that the cassava starch/chicken gelatin composites are promising membrane materials for tissue engineering applications.

Autologous bone is the gold standard in regeneration processes. However, there is an endless search for alternative materials in bone regeneration. Xenografts can act as bone substitutes given the difficulty of obtaining bone tissue from patients and before the limitations in the availability of homologous tissue donors. Bone neoformation was studied in critical-size defects created in the parietal bone of 40 adult male Wistar rats, implanted with xenografts composed of particulate bovine hydroxyapatite (HA) and with blocks of bovine hydroxyapatite (HA) and Collagen, which introduces crystallinity to the materials. The Fourier-transform infrared spectroscopy (FTIR) analysis demonstrated the carbonate and phosphate groups of the hydroxyapatite and the amide groups of the collagen structure, while the thermal transitions for HA and HA/collagen composites established mainly dehydration endothermal processes, which increased (from 79 °C to 83 °C) for F2 due to the collagen presence. The xenograft's X-ray powder diffraction (XRD) analysis also revealed the bovine HA crystalline structure, with a prominent peak centered at 32°. We observed macroporosity and mesoporosity in the xenografts from the morphology studies with heterogeneous distribution. The two xenografts induced neoformation in defects of critical size. Histological, histochemical, and scanning electron microscopy (SEM) analyses were performed 30, 60, and 90 days after implantation. The empty defects showed signs of neoformation lower than 30% in the three periods, while the defects implanted with the material showed partial regeneration. InterOss Collagen material temporarily induced osteon formation during the healing process. The results presented here are promising for bone regeneration, demonstrating a beneficial impact in the biomedical field.

Electrospun fibers of poly (lactic acid) (PLA) containing 10 and 20 wt% of bioactive glass (n-BG) and magnesium oxide (n-MgO) nanoparticles of ca. 27 and 23 nm respectively, were prepared toward to application in bone tissue engineering. The addition of both nanoparticles into the PLA will produce a synergic effect increasing its bioactivity and antimicrobial behavior. Neat PLA scaffold and the composites with MgO showed an average fiber diameter of 1.7 ± 0.6 μm, PLA/n-BG and PLA/n-BG/n-MgO fibers presented a significant diameter increase reaching values of ca. 3.1 ± 0.8 μm. Young's modulus of the electrospun scaffolds was affected by the direct presence of the particle and scaffold morphologies. All the composites having n-BG presented bioactivity through the precipitation of hydroxyapatite structures on the surface. Although n-MgO did not add bioactivity to the PLA fibers, they were able to render antimicrobial characteristics reducing the S. aureus viability around 30%, although an effect on E. coli strain was not observed. PLA/n-BG nanocomposites did not display any significant antimicrobial behavior. The different composites increased the alkaline phosphatase (ALP) expression as compared with pure PLA barely affecting the cell viability, meaning a good osteoblastic phenotype expression capacity, with PLA/n-BG presenting the highest osteoblastic expression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Several drugs are chemically unstable in the gastric environment and have low bioavailability restricted by intestinal absorption, which motivates the development of alternative routes for drug release, such as transdermal drug carriers for drug delivery to specific areas of the skin. Herein, novel polyelectrolyte complexes (PEC) consisting of carboxymethylagarose (CMA) and chitosan (CS) were prepared. pH-responsive CMA/CS hydrogels were obtained by mixing CMA and CS at various weight ratios. Swelling ratio was modulated by varying the CMA and CS weight ratio, and the highest swelling values were achieved for 2:1 wt% hydrogels at 25 °C and pH 6.0. PEC films were characterized by ATR-FTIR spectroscopy, TGA, DSC, and SEM. Results indicated that CMA and CS were successfully crosslinked by ionic complexation. As a model drug, diclofenac sodium (DS) was loaded in CMA/CS PECs. Association efficiency and loading capacity were ca. 69% and 79%, respectively, exhibiting 67% cumulative release after 72 h at 37 °C and pH 6.0 through Fickian diffusion mechanism. Viability assay of immortalized human keratinocyte (HaCat) cells showed ca. 100% survival in the presence of hydrogels and DS. Therefore, this work suggests that CMA/CS PECs can be applied as pH-responsive carriers for dermal drug delivery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Spectroscopies analysis indicated that kefiran contains branched hexasaccharide repeating units. Neat kefiran films, 2 and 5% w/w of glycerol, d-glucitol, d-galactitol, d-mannitol, and d-limonene were incorporated as plasticizers. Neat and plasticized kefiran films were characterized by physical, thermal, mechanical, optical, and water solubilization properties. Neat kefiran had a glass transition temperature (T g ) of -20 ± 2 °C and, with the addition of plasticizers between -15 to -17 ± 2 °C. The values were close to the neat kefiran, and the results could be attributed to a lower amount of plasticizer used. The solubility of the glycerol plasticized films increases by 33% and decreased with the concentration of other plasticizers in comparison with the neat kefiran. d-glucitol and d-galactitol decreased the microhardness and Young's Modulus of films around 30% and 74% respectively, obtaining more flexible kefiran films. Kefiran based films could find applications as potential materials in the food-packaging industry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Motivation: Image-based profiling combines high-throughput screening with multiparametric feature analysis to capture the effect of perturbations on biological systems. This technology has attracted increasing interest in the field of plant phenotyping, promising to accelerate the discovery of novel herbicides. However, the extraction of meaningful features from unlabeled plant images remains a big challenge., Results: We describe a novel data-driven approach to find feature representations from plant time-series images in a self-supervised manner by using time as a proxy for image similarity. In the spirit of transfer learning, we first apply an ImageNet-pretrained architecture as a base feature extractor. Then, we extend this architecture with a triplet network to refine and reduce the dimensionality of extracted features by ranking relative similarities between consecutive and non-consecutive time points. Without using any labels, we produce compact, organized representations of plant phenotypes and demonstrate their superior applicability to clustering, image retrieval and classification tasks. Besides time, our approach could be applied using other surrogate measures of phenotype similarity, thus providing a versatile method of general interest to the phenotypic profiling community., Availability and Implementation: Source code is provided in https://github.com/bayer-science-for-a-better-life/plant-triplet-net., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Studies of Trochila (Leotiomycetes, Helotiales, Cenangiaceae) are scarce. Here, we describe two new species based on molecular phylogenetic data and morphology. Trochilabostonensis was collected at the Boston Harbor Islands National Recreation Area, Massachusetts. It was found on the stem of Asclepiassyriaca , representing the first report of any Trochila species from a plant host in the family Apocynaceae. Trochilaurediniophila is associated with the uredinia of the rust fungus Ceroteliumfici . It was discovered during a survey for rust hyperparasites conducted at the Arthur Fungarium, in a single sample from 1912 collected in Trinidad. Macro- and micromorphological descriptions, illustrations, and molecular phylogenetic analyses are presented. The two new species are placed in Trochila with high support in both our six-locus (SSU, ITS, LSU, rpb1 , rpb2 , tef1 ) and two-locus (ITS, LSU) phylogenetic reconstructions. In addition, two species are combined in Trochila : Trochilacolensoi (formerly placed in Pseudopeziza ) and T.xishuangbanna (originally described as the only species in Calycellinopsis ). This study reveals new host plant families, a new ecological strategy, and a new country record for the genus Trochila . Finally, our work emphasizes the importance of specimens deposited in biological collections such as fungaria., (Paula Andrea Gómez-Zapata, Danny Haelewaters, Luis Quijada, Donald H. Pfister, M. Catherine Aime.)

The use of dyes at an industrial level has become problematic, since the discharge of dye effluents into water disturbs the photosynthetic activity of numerous aquatic organisms by reducing the penetration of light and oxygen, in addition to causing carcinogenic diseases and mutagenic effects in humans, as well as alterations in different ecosystems. Chitosan (CS) is suitable for removing anionic dyes since it has favorable properties, such as acquiring a positive charge and a typical macromolecular structure of polysaccharides. In this study, the optimization of CS beads crosslinked with glutaraldehyde (GA) for the adsorption of reactive blue dye 4 (RB4) in an aqueous solution was carried out. In this sense, the response surface methodology (RSM) was applied to evaluate the concentration of CS, GA, and sodium hydroxide on the swelling degree in the GA-crosslinked CS beads. In the same way, RSM was applied to optimize the adsorption process of the RB4 dye as a function of the initial pH of the solution, initial concentration of the dye, and adsorbent dose. The crosslinking reaction was investigated by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), and X-ray diffractometry (XRD). The design described for the swelling degree showed an R 2 (coefficient of determination) adjusted of 0.8634 and optimized concentrations (CS 3.3% w/v , GA 1.7% v/v , and NaOH 1.3 M) that were conveniently applied with a concentration of CS at 3.0% w/v to decrease the viscosity and facilitate the formation of the beads. In the RB4 dye adsorption design, an adjusted R 2 (0.8280) with good correlation was observed, where the optimized conditions were: pH = 2, adsorbent dose 0.6 g, and initial concentration of RB4 dye 5 mg/L. The kinetic behavior and the adsorption isotherm allowed us to conclude that the GA-crosslinked CS beads' adsorption mechanism was controlled mainly by chemisorption interactions, demonstrating its applicability in systems that require the removal of contaminants with similar structures to the model presented.

Bioglass nanoparticles (n-BGs, 54SiO 2 :40CaO:6P 2 O 5 mol %) with about 27 nm diameter were synthesized by the sol-gel method and incorporated into a poly(lactic acid) (PLA) matrix by the melting process in order to obtain nanocomposites with filler contents of 5, 10, and 25 wt %. Our results showed that during the cooling scan, the crystallization temperature (T c ) of the PLA/n-BG nanocomposites decreased 13°C as compared to neat PLA. The presence of nanoparticles also decreased the thermal stability of the PLA matrix, as nanocomposites presented up to about 20°C lower degradation temperatures in a nitrogen atmosphere. The presence of n-BG increased the stiffness of the polymer matrix, and for instance the composite with 25 wt % of filler presented about 52.6% higher Young's modulus than neat PLA. n-BG incorporation into PLA increased also the hydrolytic degradation of the polymer over time. When the PLA composites were immersed in simulated body fluid, an apatite layer was formed on their surface, as verified by Fourier transform infrared, X-Ray Diffraction (XRD), and scanning electron microscopy-EDS, showing that the presence of n-BG induced bioactivity on the PLA matrix. Moreover, the viability of cervical uterine adenocarcinoma cells was higher on PLA/n-BG nanocomposite with 25 wt % of filler. The presence of n-BG barely gave an antibacterial effect on the polymer matrix, despite the well-known biocidal properties of these nanoparticles. Our results show that the presence of n-BGs is a proper route for improving the bioactivity of PLA with potential application in tissue engineering., (© 2020 Wiley Periodicals, Inc.)

Low-density polyethylene composites containing different sizes of calcium oxide (CaO) nanoparticles were obtained by melt mixing. The CaO nanoparticles were synthesized by either the sol-gel or sonication methods, obtaining two different sizes: ca. 55 nm and 25 nm. These nanoparticles were used either as-synthesized or were modified organically on the surface with oleic acid (Mod-CaO), at concentrations of 3, 5, and 10 wt% in the polymer. The Mod-CaO nanoparticles of 25 nm can act as nucleating agents, increasing the polymer's crystallinity. The Young's Modulus increased with the Mod-CaO nanoparticles, rendering higher reinforcement effects with an increase as high as 36%. The reduction in Escherichia coli bacteria in the nanocomposites increased with the amount of CaO nanoparticles, the size reduction, and the surface modification. The highest antimicrobial behavior was found in the composites with a Mod-CaO of 25 nm, presenting a reduction of 99.99%. This strong antimicrobial effect can be associated with the release of the Ca 2+ from the composites, as studied for the composite with 10 wt% nanoparticles. The ion release was dependent on the size of the nanoparticles and their surface modification. These findings show that CaO nanoparticles are an excellent alternative as an antimicrobial filler in polymer nanocomposites to be applied for food packaging or medical devices.

Scaffold development for cell regeneration has increased in recent years due to the high demand for more efficient and biocompatible materials. Nanomaterials have become a critical alternative for mechanical, thermal, and antimicrobial property reinforcement in several biopolymers. In this work, four different chitosan (CS) bead formulations crosslinked with glutaraldehyde (GLA), including titanium dioxide nanoparticles (TiO 2 ), and graphene oxide (GO) nanosheets, were prepared with potential biomedical applications in mind. The characterization of by FTIR spectroscopy, X-ray photoelectron spectroscopy (XRD), thermogravimetric analysis (TGA), energy-dispersive spectroscopy (EDS) and scanning electron microscopy (SEM), demonstrated an efficient preparation of nanocomposites, with nanoparticles well-dispersed in the polymer matrix. In vivo, subdermal implantation of the beads in Wistar rat's tissue for 90 days showed a proper and complete healing process without any allergenic response to any of the formulations. Masson's trichrome staining of the histological implanted tissues demonstrated the presence of a group of macrophage/histiocyte compatible cells, which indicates a high degree of biocompatibility of the beads. The materials were very stable under body conditions as the morphometry studies showed, but with low resorption percentages. These high stability beads could be used as biocompatible, resistant materials for long-term applications. The results presented in this study show the enormous potential of these chitosan nanocomposites in cell regeneration and biomedical applications.

Red Tilapia is one of the most consumed but perishable fish in the world. As a result, it requires preservation methods for safe consumption without affecting its organoleptic characteristics. Chitosan encapsulating essential oils have shown to be an excellent food conservation method. For that reason, we carried out the study of the protective effect on red Tilapia fillets with chitosan beads (CB) incorporated with Thymus capitatus (TCEO) essential oil at 500, 1000, and 2000 mg/L to assess the conservation of the fillets. The TCEO composition was characterized by gas chromatography-mass spectrometry (CG-MS). For the other side, CB was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), thermogravimetric analysis (TGA), and Scanning electron microscopy (SEM). The protective effect of the beads was tested against the Gram-positive and Gram-negative bacteria growth for four weeks. The results showed an inhibition effect in Gram-positive bacteria at higher TCEO concentration (1000 and 2000 mg/L). Besides that, the pH, total volatile basic nitrogen (T-BNV-N), color, and fillet texture were evaluated as quality attributes. The results suggested that the incorporation of the CB-TCEO allowed a higher contact of the active compounds with the food surface, which reflected more excellent stability. The quality attributes of the fillets were preserved for 26 days, suggesting its uses for the treatment for perishable food.

Novel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer polyethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated 98.51 % of 2ME while liberation of 2ME was constant during 7 days at pH 2, 5 and 7.35. Finally, the MgO-PEG-2ME NPs decreased the viability of the prostate cancer cell line LNCap suggesting that this nanocomposite is suitable as a drug delivery system for anticancer prostate therapy., Competing Interests: The authors have declared that no competing interests exist.

The flexibility in polymer properties has allowed the development of a broad range of materials with electroactivity, such as intrinsically conductive conjugated polymers, percolated conductive composites, and ionic conductive hydrogels. These smart electroactive polymers can be designed to respond rationally under an electric stimulus, triggering outstanding properties suitable for biomedical applications. This review presents a general overview of the potential applications of these electroactive smart polymers in the field of tissue engineering and biomaterials. In particular, details about the ability of these electroactive polymers to: (1) stimulate cells in the context of tissue engineering by providing electrical current; (2) mimic muscles by converting electric energy into mechanical energy through an electromechanical response; (3) deliver drugs by changing their internal configuration under an electrical stimulus; and (4) have antimicrobial behavior due to the conduction of electricity, are discussed.

CaCO₃ nanoparticles of around 60 nm were obtained by a co-precipitation method and used as filler to prepare low-density polyethylene (LDPE) composites by melt blending. The nanoparticles were also organically modified with oleic acid (O-CaCO₃) in order to improve their interaction with the LDPE matrix. By adding 3 and 5 wt% of nanofillers, the mechanical properties under tensile conditions of the polymer matrix improved around 29%. The pure LDPE sample and the nanocomposites with 5 wt% CaCO₃ were photoaged by ultraviolet (UV) irradiation during 35 days and the carbonyl index (CI), degree of crystallinity (χ c ), and Young's modulus were measured at different times. After photoaging, the LDPE/CaCO₃ nanocomposites increased the percent crystallinity (χ c ), the CI, and Young's modulus as compared to the pure polymer. Moreover, the viscosity of the photoaged nanocomposite was lower than that of photoaged pure LDPE, while scanning electron microscopy (SEM) analysis showed that after photoaging the nanocomposites presented cavities around the nanoparticles. These difference showed that the presence of CaCO₃ nanoparticles accelerate the photo-degradation of the polymer matrix. Our results show that the addition of CaCO₃ nanoparticles into an LDPE polymer matrix allows future developments of more sustainable polyethylene materials that could be applied as films in agriculture. These LDPE-CaCO₃ nanocomposites open the opportunity to improve the low degradation of the LDPE without sacrificing the polymer's behavior, allowing future development of novel eco-friendly polymers., Competing Interests: The authors declare no conflict of interest.

Target residence time is emerging as an important optimization parameter in drug discovery, yet target and off-target engagement dynamics have not been clearly linked to the clinical performance of drugs. Here we developed high-throughput binding kinetics assays to characterize the interactions of 270 protein kinase inhibitors with 40 clinically relevant targets. Analysis of the results revealed that on-rates are better correlated with affinity than off-rates and that the fraction of slowly dissociating drug-target complexes increases from early/preclinical to late stage and FDA-approved compounds, suggesting distinct contributions by each parameter to clinical success. Combining binding parameters with PK/ADME properties, we illustrate in silico and in cells how kinetic selectivity could be exploited as an optimization strategy. Furthermore, using bio- and chemoinformatics we uncovered structural features influencing rate constants. Our results underscore the value of binding kinetics information in rational drug design and provide a resource for future studies on this subject.

A water soluble derivative in 98% yield with 23.1% incorporation of maleoyl groups was obtained by esterification of agarose with maleic anhydride. Graft copolymers were synthesized through vinyl groups of maleoylagarose with N-isopropylacrylamide using ceric ammonium nitrate or ammonium persulfate as initiator, by conventional method or microwave irradiation. High nitrogen content (4.6%) was obtained in the grafting process using ceric ammonium nitrate as initiator without microwave irradiation. Copolymers were characterized by FT-IR and NMR spectroscopies, TGA, DSC and morphological analysis by AFM and SEM microscopy, confirming the grafting of PNIPAAm onto polysaccharide backbone. Hydrogel films were obtained by ionic complexation between opposite charged groups of maleoylagarose-g-poly(N-isopropylacrylamide) and chitosan. The swelling of 1:1w/v maleoylagarose-g-PNIPAAm:chitosan film was higher than 2:1w/v film at 25 and 37°C. 53% release in vitro of diclofenac sodium from 1:1w/v maleoylagarose-g-PNIPAAm:chitosan was obtained at 37°C and pH 6.0 with <0.5 diffusional constant values., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying, cell-to-cell variability of mitochondrial morphology and energetic stress states. Overall, our modeling approach integrates biochemical and imaging knowledge, and presents a novel open-modeling approach to investigate how spatial and temporal mitochondrial dynamics contribute to functional homeostasis, and how subcellular organelle heterogeneity contributes to the emergence of cell heterogeneity., Competing Interests: The authors have declared that no competing interests exist.

Background: Differences in immune profile between actinic cheilitis (AC), a precursor of lip squamous cell carcinoma, and normal lip vermillion (NL) have not been elucidated., Objectives: To compare density, distribution, and ratios of CD8+ and FoxP3+ cells between AC and NL and assess their associations with clinicopathologic variables., Methods: Samples of AC and NL obtained between 2001 and 2013 at the College of Dentistry of the University of Concepcion, Chile, were retrospectively analyzed for immunohistochemical detection of CD8+ and FoxP3+ cells. Differences between groups were tested by Mann-Whitney U and Fisher's exact tests. Independent effects of cell densities and CD8/FoxP3 ratio with AC were assessed by multiple logistic regression analysis after adjustment for potential confounding., Results: A total of 62 AC and 24 NL biopsies were included. Densities of CD8+ and FoxP3+ cells in AC were significantly higher than in NL. Conversely, the CD8+/FoxP3+ ratio was significantly lower in AC as compared to NL. After adjustment for sun exposure, age, gender, and smoking status, a stromal FoxP3+ cell density higher than 0.35 cells/field was significantly associated with increased odds of AC (odds ratio [OR] = 5.01, 95% confidence interval [CI]: 1.18-21.31), while a stromal CD8+/FoxP3+ ratio higher than 5.91 was associated with decreased odds of AC (OR = 0.29, 95% CI: 0.08-1.08)., Conclusions: AC is characterized by increased FoxP3+ cell infiltration and a reduced CD8/FoxP3 ratio as compared to NL. Therefore, increased infiltration of FoxP3+ cells relative to CD8+ cells may contribute to the transition from normal to preneoplastic stages in lip carcinogenesis., (© 2016 The International Society of Dermatology.)

Silver nanofibers (Ag-Nfbs)~80nm in diameter were synthesized by hydrothermal treatment. The nanofibers (3 and 5wt%) were added in the initial feed together with the catalytic system. Polymerizations in an ethylene atmosphere were performed, yielding PE nanocomposites in situ with 3 and 5wt% content of Ag-Nfbs. The antibacterial effect of the silver-nanofiber composites was evaluated after incubation of Escherichia coli ATCC 25923 for 8h on their surface. Bacterial viability tests showed that the silver-nanofiber composites inhibited the growth of Escherichia coli ATCC 25923 by 88 and 56%. This behavior is attributed to increased silver ions release from the nanocomposite. TEM analysis showed that the antibacterial effect is associated with membrane disruption but not with changes in shape., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: TFEB (transcription factor EB) regulates metabolic homeostasis through its activation of lysosomal biogenesis following its nuclear translocation. TFEB activity is inhibited by mTOR phosphorylation, which signals its cytoplasmic retention. To date, the temporal relationship between alterations to mTOR activity states and changes in TFEB subcellular localization and concentration has not been sufficiently addressed., Methods: mTOR was activated by renewed addition of fully-supplemented medium, or inhibited by Torin1 or nutrient deprivation. Single-cell TFEB protein levels and subcellular localization in HeLa and MCF7 cells were measured over a time course of 15 hours by multispectral imaging cytometry. To extract single-cell level information on heterogeneous TFEB activity phenotypes, we developed a framework for identification of TFEB activity subpopulations. Through unsupervised clustering, cells were classified according to their TFEB nuclear concentration, which corresponded with downstream lysosomal responses., Results: Bulk population results revealed that mTOR negatively regulates TFEB protein levels, concomitantly to the regulation of TFEB localization. Subpopulation analysis revealed maximal sensitivity of HeLa cells to mTOR activity stimulation, leading to inactivation of 100 % of the cell population within 0.5 hours, which contrasted with a lower sensitivity in MCF7 cells. Conversely, mTOR inhibition increased the fully active subpopulation only fractionally, and full activation of 100 % of the population required co-inhibition of mTOR and the proteasome. Importantly, mTOR inhibition activated TFEB for a limited duration of 1.5 hours, and thereafter the cell population was progressively re-inactivated, with distinct kinetics for Torin1 and nutrient deprivation treatments., Conclusion: TFEB protein levels and subcellular localization are under control of a short-term rheostat, which is highly responsive to negative regulation by mTOR, but under conditions of mTOR inhibition, restricts TFEB activation in a manner dependent on the proteasome. We further identify a long-term, mTOR-independent homeostatic control negatively regulating TFEB upon prolonged mTOR inhibition. These findings are of relevance for developing strategies to target TFEB activity in disease treatment. Moreover, our quantitative approach to decipher phenotype heterogeneity in imaging datasets is of general interest, as shifts between subpopulations provide a quantitative description of single cell behaviour, indicating novel regulatory behaviors and revealing differences between cell types.

Poly(lactic acid) (PLA) composites with titanium oxide (TiO2) ~10-nm nanoparticles were produced by the melting process and their main properties were evaluated. The nanoparticles are homogeneously dispersed in the matrix with a low degree of agglomeration, as seen by transmission electron microscopy (TEM). The crystallinity temperature increased ~12% when 5 wt.% of TiO2 was added, showing that the nanoparticles acted as nucleating agents this trend was confirmed by optical images. The elastic modulus increased ~54% compared to neat PLA at 5 wt.% of nanoparticles. Despite these improvements, PLA/TiO2 nanocomposites showed lower shear viscosity than neat PLA, possibly reflecting degradation of the polymer due to the particles. Regarding biocidal properties, after 2h of contact the PLA/TiO2 composites with 8 wt.% TiO2 showed a reduction of Escherichia coli colonies of ~82% under no UVA irradiation compared to pure PLA. This biocidal characteristic can be increased under UVA irradiation, with nanocomposites containing 8 wt.% TiO2 killing 94% of the bacteria. The PLA/TiO2 nanocomposites with 8 wt.% were also 99.99% effective against Aspergillus fumigatus under the UVA irradiation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this study, an antibacterial, but not cytotoxic nanomaterial based on polyethylene and copper nanoparticles was prepared by in situ polymerization. PE-CuNps nanocomposites against Escherichia coli, completely suppressed the number of live bacteria after 12 h incubation compared to neat PE. TEM images showed that nanocomposites damage the plasma membrane of the bacteria, revealing a bacteriolytic effect. Toxic effects of copper nanoparticles on viability of neuroblastoma line cell also was evaluated, revealing a non cytotoxic effect for the doses used, showing that this nanocomposite is a ideal material for medical devices.

Since infection is a major cause of death in a patient whose immune responses have been compromised (immunocompromised patient), considerable attention has been focused on developing materials for the prevention of infections. This has been directed primarily at suppressing or eliminating the host's endogenous microbial burden and decreasing the acquisition of new organisms. In this study, the antibacterial properties of two nanocomposites, polyethylene modified with silver nanoparticles (PE-AgNps) or copper nanoparticles (PE-CuNps), against Listeria monocytogenes have been investigated. In order to elucidate the antibacterial mechanism, specifically whether this mechanism corresponds to bactericidal or bacteriolytic activities, we have determined the extent of release of metal ions (Ag(+) and Cu(2+)) and, also, the morphology of the bacteria. The metal ion release from nanocomposites was followed by inductively coupled plasma spectrometry and the morphology of the bacteria was revealed through examination of ultramicrotomed sections of bacteria in a transmission electron microscope. The study of metal ion release from the nanocomposites shows that for both nanocomposites the amount of ions released varies with time, which initially displays a linear behavior until an asymptotic behavior is reached. Further, TEM images show that silver nanoparticles (AgNps) and copper nanoparticles (CuNps), which are released from the nanocomposites, can penetrate to the cell wall and the plasma membrane of bacteria. Resulting morphological changes involve separation of the cytoplasmic membrane from the cell wall, which is known to be an effect of plasmolysis. It was revealed that the antibacterial abilities of the two nanocomposites against L. monocytogenes are associated with both bactericidal and bacteriolytic effects., (Copyright © 2014 Elsevier B.V. All rights reserved.)

HY zeolites hydrophobized by functionalization with organosilanes are much more stable in hot liquid water than the corresponding untreated zeolites. Silylation of the zeolite increases hydrophobicity without significantly reducing the density of acid sites. This hydrophobization with organosilanes makes the zeolites able to stabilize water/oil emulsions and catalyze reactions of importance in biofuel upgrading, i.e., alcohol dehydration and alkylation of m-cresol and 2-propanol in the liquid phase, at high temperatures. While at 200 °C the crystalline structure of an untreated HY zeolite collapses in a few hours in contact with a liquid medium, the functionalized hydrophobic zeolites keep their structure practically unaltered. Detailed XRD, SEM, HRTEM, and BET analyses indicate that even after reaction under severe conditions, the hydrophobic zeolites retain their crystallinity, surface area, microporosity, and acid density. It is proposed that by preferentially anchoring hydrophobic functionalities on the external surface, the direct contact of bulk liquid water and the zeolite is hindered, thus preventing the collapse of the framework during the reaction in liquid hot water.

High mountain ecosystems are among the most sensitive environments to changes in climatic conditions occurring on global, regional and local scales. The article describes the changing conditions observed over recent years in the high mountain basin of the Claro River, on the west flank of the Colombian Andean Central mountain range. Local ground truth data gathered at 4150 m, regional data available at nearby weather stations, and satellite info were used to analyze changes in the mean and the variance, and significant trends in climatic time series. Records included minimum, mean and maximum temperatures, relative humidity, rainfall, sunshine, and cloud characteristics. In high levels, minimum and maximum temperatures during the coldest days increased at a rate of about 0.6 degrees C/decade, whereas maximum temperatures during the warmest days increased at a rate of about 1.3 degrees C/decade. Rates of increase in maximum, mean and minimum diurnal temperature range reached 0.6, 0.7, and 0.5 degrees C/decade. Maximum, mean and minimum relative humidity records showed reductions of about 1.8, 3.9 and 6.6%/decade. The total number of sunny days per month increased in almost 2.1 days. The headwaters exhibited no changes in rainfall totals, but evidenced an increased occurrence of unusually heavy rainfall events. Reductions in the amount of all cloud types over the area reached 1.9%/decade. In low levels changes in mean monthly temperatures and monthly rainfall totals exceeded + 0.2 degrees C and - 4% per decade, respectively. These striking changes might have contributed to the retreat of glacier icecaps and to the disappearance of high altitude water bodies, as well as to the occurrence and rapid spread of natural and man-induced forest fires. Significant reductions in water supply, important disruptions of the integrity of high mountain ecosystems, and dramatic losses of biodiversity are now a steady menu of the severe climatic conditions experienced by these fragile tropical environments.

Introduction: Electric burns represent a small, although severe, fraction of all accidental burns. The purpose of this work is to present three children accidentally burned while flying a kite., Case Presentation: Two boys aged 9 and 10 years, and a 10-year-old girl, were injured when they tried to rescue a kite enmeshed with high voltage public electric wires. Two of the children suffered additional trauma after falling. Transitory right bundle block developed in one patient; multiple amputations and autologous skin transplantation were performed in another patient and renal insufficiency was not documented in any patient. After 5 to 34 days of hospitalization, all patients were discharged in good health., Conclusions: A preventive program should be developed to diminish the number of kite-flying-related electric burns, and their invalidating sequels.