Truncated sialylated O-glycans, such as cell-surface carbohydrate antigen sialyl-Tn (STn) are overexpressed by several cancer types, but not by the respective normal tissues. STn expression is associated with oncogenesis and metastatic ability of cancer cells, with reduced overall survival and lack of response to chemotherapy. Advances in nanomedicine have resulted in rapid development of biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with considerable potential in cancer treatment. Therefore, in this study SPIONs coated with oleic acid (OA) or dimercaptosuccinic acid (DMSA) were developed and characterized for internalization in two breast cancer cell lines: cell line expressing the STn antigen and the corresponding control. SPIONs with an average diameter of 8 nm showed superparamagnetic behavior and high potential to be used as magnetic hyperthermia agents. OA and DMSA coating provided high stability of SPIONs in physiological conditions while not changing their main properties. NPs internalization studies showed a higher accumulation of DMSA coated NPs in the breast cancer MDA-MB-231 WT cell line. In MDA-MB-231 cell line expressing STn both coated NPs showed a similar accumulation. Therefore, STn antigen can act as a receptor capable of detecting and covalently bind to the molecules present on NPs surface and induce their cellular uptake by endocytosis.

An unprecedented approach towards oligosaccharides containing N-acetylglucosamine-N-acetylmuramic (NAG-NAM) units was developed. These novel bacterial cell wall surrogates were obtained from chitosan via a top down approach involving both chemical and enzymatic reactions. The chemical modification of chitosan using a molecular clamp based strategy, allowed obtaining N-acetylglucosamine-N-acetylmuramic (NAG-NAM) containing oligomers. Intercalation of NAM residues was confirmed through the analysis of oligosaccharide fragments from enzymatic digestion and it was found that this route affords NAG-NAM containing oligosaccharides in 33% yield. These oligosaccharides mimic the carbohydrate basic skeleton of most bacterial cell surfaces. The oligosaccharides prepared are biologically relevant and will serve as a platform for further molecular recognition studies with different receptors and enzymes of both bacterial cell wall and innate immune system. This strategy combining both chemical modification and enzymatic digestion provides a novel and simple route for an easy access to bacterial cell wall fragments – biologically important targets.

Combined perovskite/crystalline-silicon four-terminal tandem solar cells promise >30% efficiencies. Here we propose all-thin-film double-junction architectures where high-bandgap perovskite top cells are coupled to ultrathin c-Si bottom cells enhanced with light trapping. A complete optoelectronic model of the devices was developed and applied to determine the optimal intermediate layers, which are paramount to maximize the cells’ photocurrent. It was ascertained that by replacing the transparent conductive oxides by grid-based metallic contacts in the intermediate positions, the parasitic absorption is lowered by 30%. Overall, a 29.2% efficiency is determined for ∼2 um thick tandems composed of the optimized interlayers and improved with Lambertian light trapping.

Twelve biochars from forest and agri-food wastes (pruning of Quercus ilex, Eucalyptus grandis, Pinus pinaster, Quercus suber, Malus pumila, Prunus spinosa, Cydonia oblonga, Eriobotrya japonica, Juglans regia, Actinidia deliciosa, Citrus sinensis and Vitis vinifera) were investigated as potential low-cost and renewable adsorbents for removal of a commonly used pharmaceutical, fluoxetine. Preliminary adsorption experiments allowed to select the most promising adsorbents, Quercus ilex, Cydonia oblonga, Eucalyptus, Juglans regia and Vitis vinifera pruning material. They were characterized by proximate, elemental and mineral analysis, thermogravimetric analysis, Fourier transform infrared spectroscopy, determination of specific surface area and pH at the point of zero charge. Batch and equilibrium studies were performed, and the influence of pH was evaluated. The equilibrium was reached in less than 15 min in all systems. The maximum adsorption capacity obtained was 6.41 mg/g for the Eucalyptus biochar, which also demonstrated a good behavior in continuous mode (packed column).

Dodecamolydbophosphoric acid (HPMo) immobilized on USY zeolite was used as a catalyst for the acetalization of glycerol with pentanal at 70 °C. Catalysts were prepared with different amounts of heteropolyacid, and the most active sample was the HPMo2@Y catalyst (1.1 wt.%). The products of glycerol acetalization with pentanal were (2-butyl-1,3-dioxolan-4-yl)methanol, a five-member ring compound, and 2-butyl-1,3-dioxan-5-ol, a six-member ring compound. Good values of selectivity for the five-member ring compound (80–85%) were obtained with all materials. The reaction conditions were optimized using HPMo2@Y as a catalyst. The optimal conditions were determined to be 70 °C reaction temperature with 0.3 g catalyst and a 1:2.5 M ratio of glycerol to pentanal. The catalytic stability of HPMo2@Y was studied. The acetalization of glycerol with pentanal was performed using the same sample. High catalytic activity for HPMo2@Y was observed.

Human aldehyde oxidase (hAOX1) is a molybdenum enzyme with high toxicological importance, but its physiological role is still unknown. hAOX1 metabolizes different classes of xenobiotics and is one of the main drug-metabolizing enzymes in the liver, along with cytochrome P450. hAOX1 oxidizes and inactivates a large number of drug molecules and has been responsible for the failure of several phase I clinical trials. The interindividual variability of drug-metabolizing enzymes caused by single nucleotide polymorphisms (SNPs) is highly relevant in pharmaceutical treatments. In this study, we present the crystal structure of the inactive variant G1269R, revealing the first structure of a molybdenum cofactor (Moco)-free form of hAOX1. These data allowed to model, for the first time, the flexible Gate 1 that controls access to the active site. Furthermore, we inspected the thermostability of wild-type hAOX1 and hAOX1 with various SNPs (L438V, R1231H, G1269R or S1271L) by CD spectroscopy and ThermoFAD, revealing that amino acid exchanges close to the Moco site can impact protein stability up to 10 °C. These results correlated with biochemical and structural data and enhance our understanding of hAOX1 and the effect of SNPs in the gene encoding this enzyme in the human population. Enzymes Aldehyde oxidase (EC1.2.3.1); xanthine dehydrogenase (EC1.17.1.4); xanthine oxidase (EC1.1.3.2). Databases Structural data are available in the Protein Data Bank under the accession number 6Q6Q.

In recent years, the discovery of the excellent optical and electrical properties of perovskite solar cells (PSCs) made them a main focus of research in photovoltaics, with efficiency records increasing astonishingly fast since their inception. However, problems associated with the stability of these devices are hindering their market application. UV degradation is one of the most severe issues, chiefly caused by TiO2’s photogenerated electrons that decompose the perovskite absorber material, coupled with the additional intrinsic degradation of this material under UV exposure. The solution presented here can minimize this effect while boosting the cells’ generated photocurrent, by making use of combined light-trapping and luminescent down-shifting effects capable of changing the harmful UV radiation to higher wavelengths that do not affect the stability and can be effectively “trapped” in the cell. This work focuses in the optimization of the photocurrent gains that can be attained by emulating the changed spectrum resulting from applying down-shifting media as encapsulant in photonic-enhanced PSCs, as well as the reduction in the harmful effects of UV radiation on the devices. Such optimized photonic solution allows current enhancement while reducing the harmful UV photocarrier generation both in the TiO2 (by 1 order of magnitude) and in the perovskite (by 80%) relative to a standard PSC without light management.

The optical properties of localized surface plasmon resonances (LSPR) sustained by self-assembled silver nanoparticles are of great interest for enhancing light trapping in thin film photovoltaics. First, we report on a systematic investigation of the structural and the optical properties of silver nanostructures fabricated by a solid-state dewetting process on various substrates. Our study allows to identify fabrication conditions in which circular, uniformly spaced nanoparticles are obtainable. The optimized NPs are then integrated into plasmonic back reflector (PBR) structures. Second, we demonstrate a novel procedure, involving a combination of opto-electronic spectroscopic techniques, allowing for the quantification of useful and parasitic absorption in thin photovoltaic absorber deposited on top of the PBR. We achieve a significant broadband useful absorption enhancement of 90% for 0.9 µm thick μc-Si:H film and demonstrate that optical losses due to plasmonic scattering are insignificant below 730 nm. Finally, we present a successful implementation of a plasmonic light trapping scheme in a thin film a-Si:H solar cell. The quantum efficiency spectra of the devices show a pronounced broadband enhancement resulting in remarkably high short circuit current densities (Jsc).

Profiled membranes (also known as corrugated membranes, micro-structured membranes, patterned membranes, membranes with designed topography or notched membranes) are gaining increasing academic and industrial attention and recognition as a viable alternative to flat membranes. So far, profiled ion exchange membranes have shown to significantly improve the performance of reverse electrodialysis (RED), and particularly, electrodialysis (ED) by eliminating the spacer shadow effect and by inducing hydrodynamic changes, leading to ion transport rate enhancement. The beneficial effects of profiled ion exchange membranes are strongly dependent on the shape of their profiles (corrugations/patterns) as well as on the flow rate and salts’ concentration in the feed streams. The enormous degree of freedom to create new profile geometries offers an exciting opportunity to improve even more their performance. Additionally, the advent of new manufacturing methods in the membrane field, such as 3D printing, is anticipated to allow a faster and an easier way to create profiled membranes with different and complex geometries.

Summary The emergence of bacterial resistance to different antibiotics in clinical use, together with the knowledge on the mechanisms by which bacteria resist the action of aminoglycosides, have contributed to the renewed interest in these molecules as potential antimicrobials. Here, we give an overview on natural and semisynthetic aminoglycosides and their structural features and modes of action, focusing on the structural insight underlying resistance mechanisms. Developments on carbohydrate chemistry and microarray technology are highlighted as powerful approaches toward generation of new aminoglycosides and for screening their interactions with RNAs and proteins. The link between antibiotic uptake and the human gut microbiome is also addressed, focusing on gut microbiome function and composition, antibiotic-induced alterations in host health, and antibiotic resistance. In addition, strategies to modulate human microbiome responses to antibiotics are discussed as novel approaches for aminoglycoside usage and for the effectiveness of antibiotic therapy.

Abstract Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability.

Abstract Aldehyde Oxidase (hAOX1) is a cytosolic enzyme involved in the metabolism of drugs and xenobiotic compounds. The enzyme belongs to the xanthine oxidase (XO) family of Mo containing enzyme and is a homo-dimer of two 150 kDa monomers. Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) of hAOX1 have been reported as affecting the ability of the enzyme to metabolize different substrates. Some of these nsSNPs have been biochemically and structurally characterized but the lack of a systematic and comprehensive study regarding all described and validated nsSNPs is urgent, due to the increasing importance of the enzyme in drug development, personalized medicine and therapy, as well as in pharmacogenetic studies. The objective of the present work was to collect all described nsSNPs of hAOX1 and utilize a series of bioinformatics tools to predict their effect on protein structure stability with putative implications on phenotypic functional consequences. Of 526 nsSNPs reported in NCBI-dbSNP, 119 are identified as deleterious whereas 92 are identified as nondeleterious variants. The stability analysis was performed for 119 deleterious variants and the results suggest that 104 nsSNPs may be responsible for destabilizing the protein structure, whereas five variants may increase the protein stability. Four nsSNPs do not have any impact on protein structure (neutral nsSNPs) of hAOX1. The prediction results of the remaining six nsSNPs are nonconclusive. The in silico results were compared with available experimental data. This methodology can also be used to identify and prioritize the stabilizing and destabilizing variants in other enzymes involved in drug metabolism.

The control of morphology and crystallinity of solution-processed perovskite thin-films for solar cells is the key for further enhancement of the devices’ power conversion efficiency and stability. Improving crystallinity and increasing grain size of perovskite films is a proven way to boost the devices’ performance and operational robustness, nevertheless this has only been achieved with high-temperature processes. Here, we present an unprecedented low-temperature (<80 °C) and ultrafast microwave (MW) annealing process to yield uniform, compact, and crystalline FA0.83Cs0.17Pb(I(1–x)Brx)3 perovskite films with full coverage and micrometer-scale grains. We demonstrate that the nominal composition FA0.83Cs0.17PbI1.8Br1.2 perovskite films annealed at 100 W MW power present the same band gap, similar morphology, and crystallinity of conventionally annealed films, with the advantage of being produced at a lower temperature (below 80 °C vs 185 °C) and during a very short period of time (∼2.5 min versus 60 min). These results open new avenues to fabricate band gap tunable perovskite films at low temperatures, which is of utmost importance for mechanically flexible perovskite cells and monolithic perovskite based tandem cells applications.

Olive pomace is a semi-solid paste resulting from the two-phase olive oil production, being the most significant waste generated by this agro-industry. Olive pomace is reported as an environmental hazard due to its high content in phenolic compounds (phytotoxic). Nevertheless, these compounds, when recovered, can have impactful actions in different human physiological conditions, namely, skin protection, dysfunction treatment or diseases prevention. Therefore, their recovery from olive pomace is crucial for environmental and economical sustainability, without forgetting the functional challenge. In a previous work, lipid and aqueous fractions of olive pomace were studied regarding its major bioactive compounds. The present research aims to describe an environmentally friendly integrated approach to extract and concentrate (by a pressure-driven membrane processing) the phytotoxic compounds of olive pomace. Three types of polymeric composite membranes (NF90, NF270 and BW30) were tested. The composition of the resulting streams (permeates and concentrates) were compared and the process efficiency assessed based on: (1) antioxidant activity and total phenolic and flavonoid contents; (2) inorganic elemental composition (by Inductively Coupled Plasma Atomic Emission Spectroscopy); (3) pH, conductivity and total organic carbon; and (4) permeate flux, membranes' apparent target solutes rejection and fouling index. The BW30 membrane presented the lowest fouling index and was the most effective for extracts concentration, with no phenolic compounds in the permeates, preventing completely the loss of such compounds.

POxylated polyurea dendrimer (PUREG4OOx48)-based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2-assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX-DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells.