Immiscible PHB/PBS and PHB/PBSA blends: morphology,phase composition and modelling of elastic modulus

This paper reports the thermal, morphological and mechanical properties of environmentally friendly poly(3-hydroxybutyrate) (PHB)/poly(butylene succinate) (PBS) and PHB/poly[(butylene succinate)-co-(butylene adipate)] (PBSA) blends, prepared by melt mixing. The blends are known to be immiscible, as also confirmed by the thermodynamic analysis here presented. A detailed quantification of the crystalline and amorphous fractions was performed, in order to interpret the mechanical properties of the blends. As expected, the ductility increased with increasing PBS or PBSA amount, but in parallel the decrease in the elastic modulus appeared limited. Surprisingly, the elastic modulus was found properly described by the rule of mixtures in the whole composition range, thus attesting mechanical compatibility between the two blend components. This unusual behavior has been explained as due to co-continuous morphology, present in a wide composition range, but also at the same time as the result of shrinkage occurring during sequential crystallization of the two components, which can lead to physical adhesion between matrix and dispersed phase. For the first time, the elastic moduli of the crystalline and mobile amorphous fractions of PBS and PBSA and of the mobile amorphous fraction of PHB at ambient temperature have been estimated through a mechanical modelling approach. © 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.     

1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells,Targeting GSK3β Kinase

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC₅₀ values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchymal transition markers, including SNAIL-1/2 and metalloproteinase-9. Moreover, flow cytometric analysis after Annexin V-FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase-3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC₅₀ values for the most active compounds against this enzyme in the micromolar range.     

Mass spectrometry in the diagnosis of thyroid disease and in the study of thyroid hormone metabolism

The importance of thyroid hormones in the regulation of development, growth, and energy metabolism is well known. Over the last decades, mass spectrometry has been extensively used to investigate thyroid hormone metabolism and to discover and characterize new molecules involved in thyroid hormones production, such as thyrotropin-releasing hormone. In the earlier period, the quantification methods, usually based on gas chromatography–mass spectrometry, were complicated and time consuming. They were mainly focused on basic research, and were not suitable for clinical diagnostics on a routine basis. The development of the modern mass spectrometers, mainly coupled to liquid chromatography, enabled simpler sample preparation procedures, and the accurate quantification of thyroid hormones, of their precursors, and of their metabolites in biological fluids, tissues, and cells became feasible. Nowadays, molecules of physiological and pathological interest can be assayed also for diagnostic purposes on a routine basis, and mass spectrometry is slowly entering the clinical laboratory. This review takes stock of the advancements in the field of thyroid metabolism that were carried out with mass spectrometry, with special focus on the use of this technique for the quantification of molecules involved in thyroid diseases.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Optimizing the lignin based synthesis of flexible polyurethane foams employing reactive liquefying agents

The present work is focused on the optimization of a green process based on the employment of by‐products obtained from wood treatments as raw materials for producing flexible polyurethane foams. More specifically, lignin was employed in flexible polyurethane foams in order to partially replace the usual fossil polyols; therefore glycerol (GLY) and glycerin polyglycidyl ether (EJ 300) were used as the polyol fraction for lignin liquefaction. Polypropylene glycol triol was used as a chain extender in different ratios with liquefaction solvents, and polymeric diphenylmethane diisocyanate as an isocyanate fraction. Liquefaction of lignin was performed by microwave irradiation, thus reducing the processing time and energy required compared to present industrial production processes. All the foams were produced in controlled expansion through the adoption of a ‘one‐shot’ approach, using water as a blowing agent and with an isocyanate index (NCO/OH) of less than 100 to improve the flexibility of the foam. This approach allowed for the substitution of up to 12% of common petro derived polyol with commercial soda lignin. Finally, the foams were characterized, presenting properties that could be modulated as a function of lignin content, GLY/EJ 300 ratio and isocyanate index. The qualities of the foams were compatible with existing materials used for furniture and for the interiors of car seats and couches. © 2015 Society of Chemical Industry     

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. Herein, we present a computational study aimed at identifying small molecules potentially able to target RBD. Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV-2 RBD and ACE2 PD might be prone to small molecule modulation, due to the hydrophilic nature of the bi-molecular recognition process and the presence of druggable hot spots. The fundamental objective is to identify, and provide to the international scientific community, hit molecules potentially suitable to enter the drug discovery process, preclinical validation and development.     

Saccharomyces cerevisiae and Hanseniaspora uvarum mixed starter cultures: Influence of microbial/physical interactions on wine characteristics

The growing trend in the wine industry is the revaluation of the role of non-Saccharomyces yeasts, promoting the use of these yeasts in association with Saccharomyces cerevisiae. Non-Saccharomyces yeasts contribute to improve wine complexity and organoleptic composition. However, the use of mixed starters needs to better understand the effect of the interaction between these species during alcoholic fermentation. The aim of this study is to evaluate the influence of mixed starter cultures, composed by combination of different S. cerevisiae and Hanseniaspora uvarum strains, on wine characteristics and to investigate the role of cell-to-cell contact on the metabolites produced during alcoholic fermentation. In the first step, three H. uvarum and two S. cerevisiae strains, previously selected, were tested during mixed fermentations in natural red grape must in order to evaluate yeast population dynamics during inoculated fermentation and influence of mixed starter cultures on wine quality. One selected mixed starter was tested in a double-compartment fermentor in order to compare mixed inoculations of S. cerevisiae/H. uvarum with and without physical separation. Our results revealed that physical contact between S. cerevisiae and H. uvarum affected the viability of H. uvarum strain, influencing also the metabolic behaviour of the strains. Although different researches are available on the role of cell-to-cell contact-mediated interactions on cell viability of the strains included in the mixed starter, to our knowledge, very few studies have evaluated the influence of cell-to-cell contact on the chemical characteristics of wine.     

A water-soluble,mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

Open image in new window

     

Adoption and Use of Software in Land Use Planning Practice: A Multiple-Country Study

Planning Support Systems (PSS) are computer-based tools that assist professionals in land use planning activities. Although several researchers acknowledge the importance of such tools in planning practice, PSS use is limited due to their poor fit to users’ needs and expectations as well as to their low usability. This article presents a study carried out in three different countries, namely, Australia, Italy, and Switzerland, aiming at investigating in-depth the current situation regarding the adoption of PSS and identifying factors preventing their wider use, devoting particular attention to the quality of such systems from the point of view of their users. The study also aimed at analyzing planners’ expectations in order to identify relevant features that PSS should provide. The main part of the study consisted of 35 interviews with planning experts. A follow-up focus group with six further participants was also performed. The results confirmed some findings of previous studies but also revealed new insights. This article provides suggestions on how to address the emerging issues, as well as pathways for creating software that can be adopted and used with satisfaction in the planning practice.