{Over the past few years porous materials have become a topic of intense research. Porous poly(ionic liquid)s combine the porous architecture with intrinsic ionic liquids properties. In all research areas, the quest for new and improved materials has targeted functional materials with enhanced specificity and efficiency towards the final application. The application of porous materials ranges from sensing, protein separation, solid-phase extraction, catalysis, to CO2 capture and reuse. Recently, the design, synthesis, and porosity control of poly (ionic liquid)s have been attempted through strategies that include classic polymerization techniques as well as molecular imprinting and aerogels production. This review aims at providing the recent advances on porous poly (ionic liquid)s, giving a critical perspective about the works in which key requirements for porosity induction are discussed. Several applications that rely on molecular interactions between the porous material and target compounds are presented, focusing mainly on CO2 capture and reuse, along with some challenges that the scientific community in this field need to be aware of.}

{Aiming to rationalize the release profile of an incorporated pharmaceutical drug in terms of its mobility, driven by guest-host interactions, the poorly water-soluble ibuprofen drug was loaded in a mesoporous inorganic silica matrix with unmodified (MCM-41) and modified surface (MCM-41sil) by post-synthesis silylation, both having pore sizes similar to 3 nm. The single calorimetric detection of a broad glass transition step for both ibuprofen com-posites indicates full drug amorphization, confirmed by the only appearance of an amorphous halo in the powder XRD patterns. Moreover, a gradient profile is disclosed by the heat flux derivative plot in the glass transition, in coherence with the thermogravimetric profile that shows a multi-step decomposition trace for confined ibuprofen in these matrixes. While identical guest dynamics, as probed by dielectric relaxation spectroscopy, were found in both dehydrated composites, a significant molecular population with faster relaxation exists in the hydrated state for the drug inside the unmodified matrix. This was rationalized as the concurrence of true confinement effects, which manifest under nanometer dimensions, and greater water affinity of the unmodified matrix, forcing the drug molecules to be placed mostly in the pore core. Finite size effects are also felt in both dehydrated composites, however guest-host interactions give origin to a dominant population with slowed down mobility that governs the overall guest dynamics. In spite of an inferior number of active sites for drug adsorption in the silylated matrix, a faster ibuprofen delivery in phosphate buffer (pH = 6.8) was observed when the drug is released from unmodified MCM-41 in the hydrated state. Therefore, our results suggest that a relevant role is played by water molecules, which impair a strong guest adsorption in the host surface more efficiently than the limited surface modification, influence the higher ratio of a faster population in the pore core and facilitate the diffusion of the aqueous releasing media inside pores.}

{Understanding the behavior of a chemical compound at a molecular level is fundamental, not only to explain its macroscopic properties, but also to enable the control and optimization of these properties. The present work aims to characterize a set of systems based on the ionic liquids {[}Aliquat]{[}Cl] and {[}Aliquat]{[}FeCl4] and on mixtures of these with different concentrations of DMSO by means of H-1 NMR relaxometry, diffusometry and X-ray diffractometry. Without DMSO, the compounds reveal locally ordered domains, which are large enough to induce order fluctuation as a significant relaxation pathway, and present paramagnetic relaxation enhancement for the {[}Aliquat]{[}Cl] and {[}Aliquat]{[}FeCl4] mixture. The addition of DMSO provides a way of tuning both the local order of these systems and the relaxation enhancement produced by the tetrachloroferrate anion. Very small DMSO volume concentrations (at least up to 1%) lead to enhanced paramagnetic relaxation without compromising the locally ordered domains. Larger DMSO concentrations gradually destroy these domains and reduce the effect of paramagnetic relaxation, while solvating the ions present in the mixtures. The paramagnetic relaxation was explained as a correlated combination of inner and outer-sphere mechanisms, in line with the size and structure differences between cation and anion. This study presents a robust method of characterizing paramagnetic ionic systems and obtaining a consistent analysis for a large set of samples having different co-solvent concentrations.}

Cancer treatment has yet to find a “silver bullet” capable of selectively and effectively kill tumor cells without damaging healthy cells. Nanomedicine is a promising field that can combine several moieties in one system to produce a multifaceted nanoplatform. The tumor microenvironment (TME) is considered responsible for the ineffectiveness of cancer therapeutics and the difficulty in the translation from the bench to bed side of novel nanomedicines. A promising approach is the use of combinatorial therapies targeting the TME with the use of stimuli-responsive nanomaterials which would increase tumor targeting. Contemporary combined strategies for TME-targeting nanoformulations are based on the application of external stimuli therapies, such as photothermy, hyperthermia or ultrasounds, in combination with stimuli-responsive nanoparticles containing a core, usually composed by metal oxides or graphene, and a biocompatible stimuli-responsive coating layer that could also contain tumor targeting moieties and a chemotherapeutic agent to enhance the therapeutic efficacy. The obstacles that nanotherapeutics must overcome in the TME to accomplish an effective therapeutic cargo delivery and the proposed strategies for improved nanotherapeutics will be reviewed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

An innovative pilot installation and eddy current testing (ECT) inspection system for laser-brazed joints is presented. The proposed system detects both surface and sub-surface welding defects operating autonomously and integrated with a robotized arm. Customized eddy current probes were designed and experimentally validated detecting pore defects with 0.13 mm diameter and sub-surface defects buried 1 mm deep. The integration of the system and the manufacturing process towards an Industry 4.0 quality control paradigm is also discussed.

Preterm birth is a major clinical and public health challenge, with a prevalence of 11% worldwide. It is the leading cause of death in children younger than five years old and represents 70% of neonatal deaths and 75% of neonatal morbidity. Despite the clinical and public health significance, this condition's aetiology is still unclear, and most of the cases are spontaneous. There are several known preterm birth risk factors, including inflammatory diseases and the genetic background, although the underlying molecular mechanisms are far from understood. The present review highlights the research advances on the association between inflammatory-related genes and the increased risk for preterm delivery. The most associated genetic variants are the TNFα rs1800629, the IL1α rs17561, and the IL1RN rs2234663. Moreover, many of the genes discussed in this review are also implicated in pathologies involving inflammatory or autoimmune systems, such as periodontal disease, bowel inflammatory disease, and autoimmune rheumatic diseases. This review presents evidence suggesting a common genetic background to preterm birth, autoimmune and inflammatory diseases susceptibility. This article is protected by copyright. All rights reserved.

Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)2-quin)2 ] (1), [VO(2,5-(Me)2-quin)2 ] (2) and [VO(2-Me-quin)2 ] (3). Complexes 1–3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H2 O2 in acetonitrile at 50◦ C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regioand bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780).

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Chronic Myeloid Leukemia (CML) is a rare malignant proliferative disease of the hematopoietic system, whose molecular hallmark is the Philadelphia chromosome (Ph). The Ph chromosome originates an aberrant fusion gene with abnormal kinase activity, leading to the buildup of reactive oxygen species and genetic instability of relevance in disease progression. Several genetic abnormalities have been correlated with CML in the blast phase, including chromosomal aberrations and common altered genes. Some of these genes are involved in the regulation of cell apoptosis and proliferation, such as the epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), or Schmidt-Ruppin A-2 proto-oncogene (SRC); cell adhesion, e.g., catenin beta 1(CTNNB1); or genes associated to TGF-β, such as SKI like proto-oncogene (SKIL), transforming growth factor beta 1 (TGFB1) or transforming growth factor beta 2 (TGFB2); and TNF-α pathways, such as Tumor necrosis factor (TNFA) or Nuclear factor kappa B subunit 1 (NFKB1). The involvement of miRNAs in CML is also gaining momentum, where dysregulation of some critical miRNAs, such as miRNA-451 and miRNA-21, which have been associated to the molecular modulation of pathogenesis, progression of disease states, and response to therapeutics. In this review, the most relevant genomic alterations found in CML will be addressed.

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Automobile laser brazing remains a complex process whose results are affected by several process variables that may result in nonacceptable welds. A multisensory customized inspection system is proposed, with two distinct non-destructive techniques: the potential drop method and eddy current testing. New probes were designed, simulated, produced, and experimentally validated in automobile's laser-brazed weld beads with artificially introduced defects. The numerical simulations allowed the development of a new four-point probe configuration in a non-conventional orthogonal shape demonstrating a superior performance in both simulation and experimental validation. The dedicated inspection system allowed the detection of porosities, cracks, and lack of bonding defects, demonstrating the redundancy and complementarity these two techniques provide.

In this work, we prepared new biocompatible N-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclo-fenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increasing the asymmetry of the ionic liquid cation/anion by growing the length of one of the alkyl chains attached to the nitrogen center/sulfonate center on the dissolution capacity of the ionic liquid. The addition of these new ionic liquids to water increased the dissolution capacity of the drugs up to four-times that in water, and improved the pharmacodynamic properties of these drugs, especially the case of sodium diclofenac. The intermolecular interactions between the drugs and ionic liquids were investigated by NMR. Two-dimensional1H/1H nuclear overhauser effect spectroscopy (NO-ESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C2Ch]2[SucAla]. In the case of paracetamol and [C4Ch][C2SO3], it was possible to observe two inter-molecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C4Ch]+. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]2−, and a N-ethyl cholinium cation, [C2Ch]+, which presented the highest ability to dissolve sodium diclofenac, showed no cytotoxicity up to 500 mM. Therefore, this ionic liquid is a potential candidate for drug delivery applications.

To investigate the effect of different halogen substituents and leaving groups and the flexibility of ligands on the anticancer activity of copper complexes, sixteen copper(ii) complexes with eight different tridentate Schiff-base ligands containing pyridine and 3,5-halogen-substituted phenol moieties were synthesized and characterized by spectroscopic methods. Four of these complexes were also characterized by X-ray crystallography. The cytotoxicity of the complexes was determined in three different tumor cell lines (i.e.the A2780 ovarian, HCT116 colorectal and MCF7 breast cancer cell line) and in a normal primary fibroblast cell line. Complexes were demonstrated to induce a higher loss of cell viability in the ovarian carcinoma cell line (A2780) with respect to the other two tumor cell lines, and therefore the biological mechanisms underlying this loss of viability were further investigated. Complexes with ligandL1(containing a 2-pycolylamine-type motif) were more cytotoxic than complexes withL2(containing a 2-(2-pyridyl)ethylamine-type motif). The loss of cell viability in A2780 tumor cells was observed in the orderCu(Cl2-L1)NO3>Cu(Cl2-L1)Cl>Cu(Br2-L1)Cl>Cu(BrCl-L1)Cl. All complexes were able to induce reactive oxygen species (ROS) that could be related to the loss of cell viability. ComplexesCu(BrCl-L1)ClandCu(Cl2-L1)NO3were able to promote A2780 cell apoptosis and autophagy and for complexCu(BrCl-L1)Clthe increase in apoptosis was due to the intrinsic pathway.Cu(Cl2-L1)ClandCu(Br2-L1)Clcomplexes lead to cellular detachment allowing to correlate with the results of loss of cell viability. Despite the ability of theCu(BrCl-L1)Clcomplex to induce programmed cell death in A2780 cells, its therapeutic window turned out to be low making theCu(Cl2-L1)NO3complex the most promising candidate for additional biological applications.

Palladacycles are versatile organometallic compounds that show potential for therapeutic use. Here are described the synthesis and characterization of mono- and dinuclear palladacycles bearing diphosphines. Their biological effect was investigated in A2780, an ovarian-derived cancer line, and in normal dermal fibroblasts. The compounds displayed selective cytotoxicity toward the A2780 cell line. Compound 3 decreased the cell viability through cell cycle retention in G0/G1, triggered apoptosis through the intrinsic pathway, and induced autophagy in A2780 cells. Compound 9 also induced cell cycle retention, apoptosis, and cellular detachment. Notably, compound 9 induced the production of intracellular reactive oxygen species (ROS). Our work demonstrated that compound 3 enters A2780 cells via active transport, which requires energy, while compound 9 enters A2780 cells mostly passively. The potential effect of palladacycles in angiogenesis was investigated for the first time in an in vivo chorioallantoic membrane model, showing that while compound 3 displayed an antiangiogenic effect crucial to fighting cancer progression, compound 9 promoted angiogenesis. These results show that palladacycles may be used in different clinical applications where pro- or antiangiogenic effects may be desirable.

Edible flowers are being used as a new ingredient in modern gastronomy. Recently, these products have also gained interest as an important source of phenolic compounds with potential for biomedical applications. The present work studied a methanolic extract of Rosa x hybrida in which 35 individual phenolic compounds were identified. The extract has been evaluated for its antiproliferative properties in ovarian carcinoma cells. Results showed that the antiproliferative effect was associated with the induction of autophagy and apoptosis with the concomitant ROS increase probably related to mitochondria dysfunction. These antiproliferative effects might be associated with some components of the extract such as quercetin. The extract did not induce damage in healthy cells and that it was able to improve the wound healing activity. The present study also evaluated the properties of the mentioned extract in vivo in C. elegans. Tests demonstrated a lack of toxicity in the worm model. Promising results have been obtained in transgenic strains of C. elegans that produce human beta amyloid peptide, suggesting the possible utility of the extract from the point of view of Alzheimer disease. Altogether, results suggest that Rosa x hybrida extracts could be a new tool for the development of functional foods.

Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2′:6′,2″-terpyridine ligand: [Pt(4′-(2-quin)-terpy)Cl](SO3CF3) (1), [Au(4′-(2-quin)-terpy)Cl](PF6)2·CH3CN (2) and [Cu(4′-(2-quin)-terpy)Cl](PF6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC50 are at least 20 × lower than the IC50 displayed by cisplatin (15.4 μM) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3, more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 >1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1–3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect.

The use of nanomaterials to improve medical diagnostics and therapeutics has been rapidly increasing. Among these materials are gold nanoparticles, which can be functionalized to target specific cells, acting as nanovectors for drug delivery, enhanced contrast agents as well as other targeted therapies. Au nanoparticles are very useful as they selectively accumulate in tumour sites due to the enhanced permeability-retention effect. There is however little information about the spatial distribution of the nanoparticles within tumours, which might hinder efficient therapies. In this study, X-ray fluorescence was used to investigate the diffusion of gold nanoparticles in cancer cell spheroids mimicking true tumour growth. Functionalization of the nanoparticles has the effect of allowing better diffusion into and out of the spheroid, while those nanoparticles that are only partially covered rapidly formed aggregates. This clustering led to size exclusion during transport within the tumour, changing its distribution profile while greatly increasing the nanoparticle concentration.

Ionogel are versatile materials, as they present the electrical properties of ionic liquids and also dimensional stability, since they are trapped in a solid matrix, allowing application in electronic devices such as gas sensors and electronic noses. In this work, ionogels were designed to act as a sensitive layer for the detection of volatiles in a custom-made electronic nose. Ionogels composed of gelatin and a single imidazolium ionic liquid were doped with bare and functionalized iron oxide nanoparticles, producing ionogels with adjustable target selectivity. After exposing an array of four ionogels to 12 distinct volatile organic compounds, the collected signals were analyzed by principal component analysis (PCA) and by several supervised classification methods, in order to assess the ability of the electronic nose to distinguish different volatiles, which showed accuracy above 98%.

Cancer is still one of the deadliest diseases worldwide despite the efforts in its early detection and treatment strategies. However, most chemotherapeutic agents still present side effects in normal tissues and acquired resistance that limit their efficacy. Spiropyrazoline oxindoles might be good alternatives as they have shown antiproliferative activity in human breast and colon cancer cell lines, without eliciting cytotoxicity in healthy cells. However, their potential for ovarian cancer was never tested. In this work, the antiproliferative activity of five spiropyrazoline oxindoles was assessed in ovarian cancer cells A2780 and the biological targets and mechanism of action of the most promising compound evaluated. Compound 1a showed the highest antiproliferative effect, as well as the highest selectivity for A2780 cells compared to healthy fibroblasts. This antiproliferative effect results from the induction of cell death by mitochondria-mediated apoptosis and autophagy. In vitro DNA interaction studies demonstrated that 1a interacts with DNA by groove-binding, without triggering genotoxicity. In addition, 1a showed a strong affinity to bovine serum albumin that might be important for further inclusion in drug delivery platforms. Proteomic studies reinforced 1a role in promoting A2780 endoplasmatic reticulum (ER) stress by destabilizing the correct protein folding which triggers cell death via apoptosis and autophagy.

As Yondelis joins the ranks of approved anti-cancer drugs, the benefit from exploring the oceans' biodiversity becomes clear. From marine toxins, relevant bioproducts can be obtained due to their potential to interfere with specific pathways. We explored the cytotoxicity of toxin-bearing secretions of the polychaete Eulalia onto a battery of normal and cancer human cell lines and discovered that the cocktail of proteins is more toxic towards an ovarian cancer cell line (A2780). The secretions' main proteins were identified by proteomics and transcriptomics: 14-3-3 protein, Hsp70, Rab3, Arylsulfatase B and serine protease, the latter two being known toxins. This mixture of toxins induces cell-cycle arrest at G2/M phase after 3h exposure in A2780 cells and extrinsic programmed cell death. These findings indicate that partial re-activation of the G2/M checkpoint, which is inactivated in many cancer cells, can be partly reversed by the toxic mixture. Protein-protein interaction networks partake in two cytotoxic effects: cell-cycle arrest with a link to RAB3C and RAF1; and lytic activity of arylsulfatases. The discovery of both mechanisms indicates that venomous mixtures may affect proliferating cells in a specific manner, highlighting the cocktails' potential in the fine-tuning of anti-cancer therapeutics targeting cell cycle and protein homeostasis.