Investigation into the Influence of the Process Parameters on the Stability of a Poly(Vinyl)-Alcohol-Based Coating System.

Most tablets put on the market are coated with polymers soluble in water. The Opadry II 85 series from Colorcon Inc., is a family of PVA-based products marketed since the 1990s. Despite numerous publications on the properties of PVA, to date, limited work has been undertaken to determine the physico-chemical parameters (i.e., UV light, high temperature, and relative humidity) that could affect the performance of PVA-based coatings. To this end, we performed artificial ageing processes on samples made of Opadry Orange II or of some selected components of this coating and analysed them by means of a multidisciplinary approach, using, for example, FTIR, NMR, rheology, and DMTA measurements. In this way, we analysed the influence of the critical components of the Opadry Orange II formula, such as titanium dioxide and aluminium hydroxide, on the coating characteristics under ageing conditions.

An Insight into the Degradation Processes of the Anti-Hypertensive Drug Furosemide.

Furosemide (FUR), an active pharmaceutical ingredient (API) belonging to a group of drugs known as loop diuretics, has widespread use, but, is characterized by a strong instability to light, which causes chemical transformations that could give a yellowing phenomenon and have a significant impact from a health and marketing point of view. Many studies have tried to explain this phenomenon under different experimental conditions, but no detailed explanation of the yellowing phenomenon has been provided. This work, unlike the others, provides an overall view and explanation of the behavior of FUR in relation to the yellowing phenomenon, both in the solution and in solid state, considering several aspects, such as light exposure, presence of oxygen, and moisture effects.

Bodily, emotional, and public sphere at the time of COVID-19. An investigation on concrete and abstract concepts.

The outbreak of Covid-19 pandemics has dramatically affected people's lives. Among newly established practices, it has likely enriched our conceptual representations with new components. We tested this by asking Italian participants during the first lockdown to rate a set of diverse words on several crucial dimensions. We found concepts are organized along a main axis opposing internal and external grounding, with fine-grained distinctions within the two categories underlining the role of emotions. We also show through a comparison with existing data that Covid-19 impacted the organization of conceptual representations. For instance, subclasses of abstract concepts that are usually distinct converge into a unitary group, characterized by emotions and internal grounding. Additionally, we found institutional and Covid-19 related concepts, for which participants felt more the need for others to understand the meaning, clustered together. Our results show that the spread of Covid-19 has simultaneously changed our lives and shaped our conceptual representations.

Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study.

In recent years, humanity has had to face a critical pandemic due to SARS-CoV-2. In the rapid search for effective drugs against this RNA-positive virus, the repurposing of already existing nucleotide/nucleoside analogs able to stop RNA replication by inhibiting the RNA-dependent RNA polymerase enzyme has been evaluated. In this process, a valid contribution has been the use of in silico experiments, which allow for a rapid evaluation of the possible effectiveness of the proposed drugs. Here we propose a molecular dynamic study to provide insight into the inhibition mechanism of Penciclovir, a nucleotide analog on the RNA-dependent RNA polymerase enzyme. Besides the presented results, in this article, for the first time, molecular dynamic simulations have been performed considering not only the RNA-dependent RNA polymerase protein, but also its cofactors (fundamental for RNA replication) and double-strand RNA.

Overusing the pacifier during infancy sets a footprint on abstract words processing.

Perturbations to the speech articulators induced by frequently using an interfering object during infancy (i.e., pacifier) might shape children's language experience and the building of conceptual representations. Seventy-one typically developing third graders performed a semantic categorization task with abstract, concrete and emotional words. Children who used the pacifier for a more extended period were slower than the others. Moreover, overusing the pacifier increased response time of abstract words, whereas emotional and (above all) concrete words were less affected. Results support the view that abstract words are grounded both in perception-action and in linguistic experience.

Trichogin GA IV Alignment and Oligomerization in Phospholipid Bilayers.

Trichogin GA IV is a short peptaibol with antimicrobial activity. This uncharged, but amphipathic, sequence is aligned at the membrane interface and undergoes a transition to an aggregated state that inserts more deeply into the membrane, an assembly that predominates at a peptide-to-lipid ratio (P/L) of 1:20. In this work, the natural trichogin sequence was prepared and reconstituted into oriented lipid bilayers. The 15 N NMR chemical shift is indicative of a well-defined alignment of the peptide parallel to the membrane surface at P/Ls of 1:120 and 1:20. When the P/L is increased to 1:8, an additional peptide topology is observed that is indicative of a heterogeneous orientation, with helix alignments ranging from around the magic angle to perfectly in-plane. The topological preference of the trichogin helix for an orientation parallel to the membrane surface was confirmed by attenuated total reflection FTIR spectroscopy. Furthermore, 19 F CODEX experiments were performed on a trichogin sequence with 19 F-Phe at position 10. The CODEX decay is in agreement with a tetrameric complex, in which the 19 F sites are about 9-9.5 Šapart. Thus, a model emerges in which the monomeric peptide aligns along the membrane surface. When the peptide concentration increases, first dimeric and then tetrameric assemblies form, made up from helices oriented predominantly parallel to the membrane surface. The formation of these aggregates correlates with the release of vesicle contents including relatively large molecules.

Molecular Sponge: pH-Driven Reversible Squeezing of Stimuli-Sensitive Peptide Monolayers.

The cyclic change of structure, thickness, and density, with pH switching from acidic (pH = 3) to basic (pH = 11) condition, has been revealed for chemisorbed monolayers of the peptide Lipo-Aib-Lys-Leu-Aib-Lys-Lys-Leu-Aib-Lys-Ile-Lol, a trichogin GA IV-analogue carrying Lys residues instead of Gly ones at positions 2, 5, 6, and 9, while a homologous peptide not containing Lys residues does not show any response to pH changes. Experimental and theoretical results, obtained by means of quartz crystal microbalance with dissipation monitoring, surface plasmon resonance, nanoplasmonic sensing technique, Fourier transform infrared-reflection attenuated spectroscopy and dynamic force spectroscopy, and molecular dynamics simulations provide detailed information on the overall monolayer structure changes with pH, including the analysis of the intra- and interchain peptide dynamics, the structure of the peptide layer/water/solid interface, as well as the position and role of solvation and nonsolvation water. The observed stimuli-responsive behavior of L1 peptide monolayers is accounted in terms of the occurrence of a pH-induced wetting/dewetting process, due to the pH-induced switching of the hydrophilic character of charged lysine groups to hydrophobic one of the same uncharged groups, along the peptide chain. This behavior in turn promotes the collective change of the aggregation state of the peptide chains. The present results may pave the way to critically reexamine the mechanism of stimuli-responsive systems.

Building Supramolecular DNA-Inspired Nanowires on Gold Surfaces: From 2D to 3D.

Three building blocks have been designed to chemically link to a gold surface and vertically self-assemble through thymine-adenine hydrogen bonds. Starting from these building blocks, two different films were engineered on gold surface. Film 1 consists of adenine linked to lipoic acid (Lipo-A) to covalently bind to the gold surface, and ZnTPP linked to a thymine (T-ZnTPP). Film 2 has an additional noncovalently linked layer: a helical undecapeptide analogue of the trichogin GA IV peptide, in which four glycines were replaced by four lysines to favor a helical conformation and reduce flexibility and the two extremities were functionalized with thymine and adenine to enable Lipo-A and T-ZnTPP binding, respectively. These films were characterized by electrochemical and spectroscopic techniques, and were very stable over time and when in contact with solution. Under illumination, they could generate current with higher efficiency than similar previously described systems.

The Influence of pH on the Scleroglucan and Scleroglucan/Borax Systems.

The effects that an increase of environmental pH has on the triple helix of scleroglucan (Sclg) and on the Sclg/borax hydrogel are reported. Rheological experiments show that the hydrogel is less sensitive to pH increase than Sclg alone, while at pH = 14 a dramatic viscosity decrease takes place for both systems. This effect is evidenced also by the reduced water uptake and anisotropic elongation detected, at pH = 14, by the swelling behaviour of tablets prepared with the Sclg/borax system. On the opposite, a different behaviour was observed with guar gum and locust bean gum tablets, tested as reference polysaccharides. The effect of pH on the structure of Sclg and Sclg/borax was investigated also by means of spectroscopic approaches based on the interaction between Congo red (CR) and the Sclg triple helix. Obtained results indicated that the CR absorbance maximum is shifted as a function of pH and by the presence of borax. Principal component analysis allowed very precise identification of the pH value at which the Sclg helix collapses. Molecular dynamics simulations of the Sclg/borax-CR complex indicated that, at physiological pH, only a few ordered configurations are populated, according to the induced circular dichroism (CD) spectrum evidence.

Self-assembly of a model peptide incorporating a hexa-histidine sequence attached to an oligo-alanine sequence, and binding to gold NTA/nickel nanoparticles.

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexa-histidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac's), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the ß-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

Tuning the chiroptical and morphological properties of steroidal-porphyrin aggregates: a mechanistic, structural, and MM investigation.

The aggregation of a steroid-functionalised porphyrin derivative occurs with the formation of J-type chiral species. Spectroscopic and SEM studies indicate that the initial concentration of the macrocycle strongly influences the morphology of the final mesoscopic structures, as a consequence of a change in the mechanistic course of the self-assembly process. Fibrillar structures are obtained at low porphyrin concentration, whereas aggregates of globular shapes are formed on increasing the substrate concentration. Molecular mechanics investigations gave insights into the intimate nature of the driving forces that govern the self-assembly process, pointing out the importance of ring distortion, of intramolecular steroidal OH-π hydrogen bonds, as well as dispersion forces among the tetrapyrrolic platforms.

Aggregation propensity of Aib homo-peptides of different length: an insight from molecular dynamics simulations.

Interactions between peptides are relevant from a biomedical point of view, in particular for the role played by their aggregates in different important pathologies, and also because peptide aggregates represent promising scaffolds for innovative materials. In the present article, the aggregation properties of the homo-peptides formed by α-aminoisobutyric acid (U) residues are discussed. The peptides investigated have chain lengths between six and 15 residues and comprise benzyl and naphthyl groups at the N- and C-termini, respectively. Spectroscopic experiments and molecular dynamics simulations show that the shortest homo-peptide, constituted by six U, does not exhibit any tendency to aggregate under the conditions examined. On the other hand, the homologous peptide with 15 U forms very stable and compact aggregates in 70/30(v/v) methanol/water solution. Atomic force microscopy images indicate that these aggregates promote formation of long fibrils once they are deposited on a mica surface. The aggregation phenomenon is mainly due to hydrophobic interactions occurring between very stable helical structures, and the aromatic groups in the peptides seem to play a minor role.

SERS nanostructures with engineered active peptides against an immune checkpoint protein.

The immune checkpoint programmed death ligand 1 (PD-L1) protein is expressed by tumor cells and it suppresses the killer activity of CD8+ T-lymphocyte cells binding to the programmed death 1 (PD-1) protein of these immune cells. Binding to either PD-L1 or PD1 is used for avoiding the inactivation of CD8+ T-lymphocyte cells. We report, for the first time, Au plasmonic nanostructures with surface-enhanced Raman scattering (SERS) properties (SERS nanostructures) and functionalized with an engineered peptide (CLP002: Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which targets PD-L1. Molecular dynamics calculations are used to describe the interaction of the targeting peptide with PD-L1 in the region where the interaction with PD-1 occurs, showing also the poor targeting activity of a peptide with the same amino acids, but a scrambled sequence. The results are confirmed experimentally since a very good targeting activity is observed against the MDA-MB-231 breast adenocarcinoma cancer cell line, which overexpresses PD-L1. A good activity is observed, in particular, for SERS nanostructures where the CLP002-engineered peptide is linked to the nanostructure surface with a short charged amino acid sequence and a long PEG chain. The results show that the functionalized SERS nanostructures show very good targeting of the immune checkpoint PD-L1.

Formulations and processing of nanocrystalline TiO2 films for the different requirements of plastic, metal and glass dye solar cell applications.

We carried out a systematic study on the effect of nanocrystalline TiO2 paste formulations and temperature treatment on the performance of dye solar cells (DSCs) over a large temperature range, to provide useful information for the fabrication of both plastic and metal flexible devices. We compared conventional screen-printable and binder-free TiO2 pastes with a new formulation which includes hydroxylethyl cellulose (HEC), enabling the study of the effect of organic materials in the TiO2 layer in the whole 25-600 °C temperature range. Differently from the binder-free formulations where the device efficiency rose monotonically with temperature, the use of cellulose binders led to remarkably different trends depending on their pyrolysis and decomposition thresholds and solubility, especially at those temperatures compatible with plastic foils. Above 325 °C, where metal foil can be used as substrates, the efficiencies become similar to those of the binder-free paste due to effective binder decomposition and inter-nanoparticle bonding. Finally, we demonstrated, for the first time, that the simultaneous application of both temperature (110-150 °C) and pressure (100 MPa) can lead to a large improvement (33%) compared to the same mechanical compression method carried out at room temperature only.

Theoretical modeling of UV-Vis absorption and emission spectra in liquid state systems including vibrational and conformational effects: the vertical transition approximation.

In this paper we describe in detail a general and efficient methodology, based on the perturbed matrix method and molecular dynamics simulations, to model UV-Vis absorption and emission spectra including vibrational and conformational effects. The basic approximation used is to consider all the chromophore atomic coordinates as semiclassical degrees of freedom, hence allowing the calculation of the complete spectral signal by using the electronic vertical transitions as obtained at each possible chromophore configuration, thus including the contributions of vibrations and conformational transitions into the spectrum. As shown for the model system utilized in this paper, solvated 1-phenyl-naphthalene, such an approximation can be rather accurate to reproduce the absorption and emission spectral line shape and properties when, as it often occurs, the vertical vibronic transition largely overlaps the other non-negligible vibronic transitions.

Grounded Cognition, Linguistic Relativity, and Abstract Concepts.

Kemmerer's paper convincingly claims that the grounded cognition model (GCM) entails linguistic relativity. Here, we underline that tackling linguistic relativity and cultural differences is vital for GCM. First, it allows GCM to focus more on flexible rather than stable aspects of cognition. Second, it highlights the centrality of linguistic experience for human cognition. While GCM-inspired research underscored the similarity between linguistic and nonlinguistic concepts, it is now paramount to understand when and how language(s) influence knowledge. To this aim, we argue that linguistic variation might be particularly relevant for more abstract concepts-which are more debatable and open to revisions.

Consensus Paper: Current Perspectives on Abstract Concepts and Future Research Directions.

concepts are relevant to a wide range of disciplines, including cognitive science, linguistics, psychology, cognitive, social, and affective neuroscience, and philosophy. This consensus paper synthesizes the work and views of researchers in the field, discussing current perspectives on theoretical and methodological issues, and recommendations for future research. In this paper, we urge researchers to go beyond the traditional abstract-concrete dichotomy and consider the multiple dimensions that characterize concepts (e.g., sensorimotor experience, social interaction, conceptual metaphor), as well as the mediating influence of linguistic and cultural context on conceptual representations. We also promote the use of interactive methods to investigate both the comprehension and production of abstract concepts, while also focusing on individual differences in conceptual representations. Overall, we argue that abstract concepts should be studied in a more nuanced way that takes into account their complexity and diversity, which should permit us a fuller, more holistic understanding of abstract cognition.

Ultrasound-Stimulated PVA Microbubbles as a Green and Handy Tool for the Cleaning of Cellulose-Based Materials.

One of the main issues in the cultural heritage field of restoration chemistry is the identification of greener and more effective methods for the wet cleaning of paper artefacts, which serve as witnesses to human history and custodians of cultural values. In this context, we propose a biocompatible method to perform wet cleaning on paper based on the use of 1 MHz ultrasound in combination with water-dispersed polyvinyl alcohol microbubbles (PVAMBs), followed by dabbing with PVA-based hydrogel. This method can be applied to both old and new papers. FTIR spectroscopy, X-ray diffraction, HPLC analysis, pH measurements and tensile tests were performed on paper samples, to assess the efficacy of the cleaning system. According to the results, ultrasound-activated PVAMB application allows for an efficient interaction with rough and porous cellulose paper profiles, promoting the removal of cellulose degradation byproducts, while the following hydrogel dabbing treatment guarantees the removal of cleaning materials residues. Moreover, the results also pointed out that after the treatment no thermal or mechanical damages had affected the paper. In conclusion, the readability of these kinds of artifacts can be improved without causing an alteration of their structural properties, while mitigating the risk of ink diffusion.

Molecular origin of the two-step mechanism of gellan aggregation.

Among hydrocolloids, gellan is one of the most studied polysaccharides due to its ability to form mechanically stable gels. Despite its long-standing use, the gellan aggregation mechanism is still not understood because of the lack of atomistic information. Here, we fill this gap by developing a new gellan force field. Our simulations offer the first microscopic overview of gellan aggregation, detecting the coil to single-helix transition at dilute conditions and the formation of higher-order aggregates at high concentration through a two-step process: first, the formation of double helices and then their assembly into superstructures. For both steps, we also assess the role of monovalent and divalent cations, complementing simulations with rheology and atomic force microscopy experiments and highlighting the leading role of divalent cations. These results pave the way for future use of gellan-based systems in a variety of applications, from food science to art restoration.

Combining a hydrogel and an electrochemical biosensor to determine the extent of degradation of paper artworks.

Paper-based artworks are among the most valuable assets for transmission of knowledge. Historical paper is composed of different polysaccharides (e.g. cellulose), binders, and glues. During aging all of these components undergo several degradation processes, as a result of external and intrinsic causes, and these can compromise the state of conservation of the document. In this work, application of a new biotechnological strategy for paper artefact preservation is reported. By making use of innovative and non-invasive materials, for example appropriate hydrogels, in combination with selective electrochemical biosensors, it is possible to simultaneously verify the degradation condition of the paper artwork and then to efficiently clean it, while monitoring the process of removal of both pollution and degradation products. In this paper, we focus on specific examples in which such techniques have been applied to paper artworks and that illustrate the advantages and potential of this biotechnology compared with the traditional paper-cleaning methods currently in use.