Development of Thermoinks for 4D Direct Printing of Temperature-Induced Self-Rolling Hydrogel Actuators

4D printing has emerged as an important technique for fabricating 3D objects from programmable materials capable of time-dependent reshaping. In the present investigation, novel 4D thermoinks composed of laponite (LAP), an interpenetrating network of poly(N-isopropylacrylamide) (PNIPAAm), and alginate (ALG) are developed for direct printing of shape-morphing structures. This approach consists of the design and fabrication of 3D honeycomb-patterned hydrogel discs self-rolling into tubular constructs under the stimulus of temperature. The shape morphing behavior of hydrogels is due to shear-induced anisotropy generated via 3D printing. The compositionally tunable hydrogel discs can be programmed to exhibit different actuation behaviors at different temperatures. Upon immersion in 12 °C water, singly crosslinked sheets roll up into a tubular construct. When transferred to 42 °C water, the tubes first rapidly unfold and then slightly curve up in the opposite direction. Through a dual photocrosslinking of PNIPAAm, it is possible to inverse temperature-dependent shape morphing and induce self-folding at higher and unrolling at lower temperatures. The extensive self-assembling motion is essential to developing thermal actuators with broad applications in, e.g., soft robotics and active implantology, whereas controllable self-rolling of planar hydrogels is of the highest interest to biomedical engineering as it allows for effective fabrication of hollow tubes.     

Influence of platelet-activating factor,lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.     

Efficient Functionalisation of Cubic Monovinylsilsesquioxanes via Cross‐Metathesis and Silylative Coupling with Olefins in the Presence of Ruthenium Complexes

Monovinylheptaisobutylsilsesquioxane undergoes efficient cross‐metathesis and silylative coupling with styrenes. Allyl derivatives were successfully tested in cross‐metathesis in the presence of first generation Grubbs’ catalyst, while heteroatom‐substituted vinyl derivatives (vinyl ethers, 9‐vinylcarbazole) efficiently undergo silylative coupling catalysed by ruthenium hydride complexes. Both reactions proceed highly stereoselectively and lead to nearly quantitative formation of E isomers. Only when vinyl ethers are used does the reaction lead to a mixture of stereoisomers. Atmospheric pressure photoionisation has been successfully used for recording mass spectra of the functionalised silsesquioxanes.     

Synthesis of Dolichols in Candida albicans Is Co-Regulated with Elongation of Fatty Acids

Protein glycosylation requires dolichyl phosphate as a carbohydrate carrier. Dolichols are α-saturated polyprenols, and their saturation in S. cerevisiae is catalyzed by polyprenyl reductase Dfg10 together with some other unknown enzymes. The aim of this study was to identify such enzymes in Candida. The Dfg10 polyprenyl reductase from S. cerevisiae comprises a C-terminal 3-oxo-5-alpha-steroid 4-dehydrogenase domain. Alignment analysis revealed such a domain in two ORFs (orf19.209 and orf19.3293) from C. albicans, which were similar, respectively, to Dfg10 polyprenyl reductase and Tsc13 enoyl-transferase from S. cerevisiae. Deletion of orf19.209 in Candida impaired saturation of polyprenols. The Tsc13 homologue turned out not to be capable of saturating polyprenols, but limiting its expression reduce the cellular level of dolichols and polyprenols. This reduction was not due to a decreased expression of genes encoding cis-prenyltransferases from the dolichol branch but to a lower expression of genes encoding enzymes of the early stages of the mevalonate pathway. Despite the resulting lower consumption of acetyl-CoA, the sole precursor of the mevalonate pathway, it was not redirected towards fatty acid synthesis or elongation. Lowering the expression of TSC13 decreased the expression of the ACC1 gene encoding acetyl-CoA carboxylase, the key regulatory enzyme of fatty acid synthesis and elongation.     

Chimeric Structures in Mental Illnesses—“Magic” Molecules Specified for Complex Disorders

Mental health problems cover a wide spectrum of diseases, including mild to moderate anxiety, depression, alcohol/drug use disorders, as well as bipolar disorder and schizophrenia. Pharmacological treatment seems to be one of the most effective opportunities to recover function efficiently and satisfactorily. However, such disorders are complex as several target points are involved. This results in a necessity to combine different types of drugs to obtain the necessary therapeutic goals. There is a need to develop safer and more effective drugs. Considering that mental illnesses share multifactorial processes, the paradigm of one treatment with multiple modes of action rather than single-target strategies would be more effective for successful therapies. Therefore, hybrid molecules that combine two pharmacophores in one entity show promise, as they possess the desired therapeutic index with a small off-target risk. This review aims to provide information on chimeric structures designed for mental disorder therapy (i.e., schizophrenia and depression), and new types of drug candidates currently being tested. In addition, a discussion on some benefits and limitations of multifunctional, bivalent drug candidates is also given.     

Effect of Alkyl Sulfate on the Phase Behavior of Microemulsions Stabilized with Monoacylglycerols

In this study the effect of an anionic surfactant (sodium dodecyl sulfate SDS) and oils (hydrocarbons: C12–C16) on the formation and phase behavior of the systems of oil/monoacylglycerols (MAG):SDS/propylene glycol/water has been investigated. The effects of the surfactant mixture on the phase behavior and the concentration of water or oil in the systems were studied at three temperatures (50, 55, 60 °C). Electrical conductivity measurement, FT-IR spectroscopy and differential scanning calorimetry methods were applied to determine the structure and type of the microemulsions formed. The dimension of microemulsion droplets was characterized by dynamic light scattering. It has been stated that the concentration of SDS has a strong influence on the shape and extent of the microemulsion areas. Addition of an ionic surfactant to the mixture with MAG promotes an increase in the area of microemulsion formation in the phase diagrams, and these areas of the isotropic region change with the temperature. It was shown that the presence in the systems of a surfactant more hydrophilic than MAG caused an increase in water content in the microemulsions. It was found that, depending on temperature and concentration of the surfactant mixture, it was possible to obtain a W/O type microemulsion with a dispersed particles size distribution ranging from 20 to 50 nm and containing about 17–38% water in the system. Among different alkanes (from C12 to C16), hexadecane embedded microemulsions showed a maximum water solubilization capacity.     

SurA-like and Skp-like Proteins as Important Virulence Determinants of the Gram Negative Bacterial Pathogens

In the Gram-negative bacteria, many important virulence factors reach their destination via two-step export systems, and they must traverse the periplasmic space before reaching the outer membrane. Since these proteins must be maintained in a structure competent for transport into or across the membrane, they frequently require the assistance of chaperones. Based on the results obtained for the model bacterium Escherichia coli and related species, it is assumed that in the biogenesis of the outer membrane proteins and the periplasmic transit of secretory proteins, the SurA peptidyl–prolyl isomerase/chaperone plays a leading role, while the Skp chaperone is rather of secondary importance. However, detailed studies carried out on several other Gram-negative pathogens indicate that the importance of individual chaperones in the folding and transport processes depends on the properties of client proteins and is species-specific. Taking into account the importance of SurA functions in bacterial virulence and severity of phenotypes due to surA mutations, this folding factor is considered as a putative therapeutic target to combat microbial infections. In this review, we present recent findings regarding SurA and Skp proteins: their mechanisms of action, involvement in processes related to virulence, and perspectives to use them as therapeutic targets.     

Elevating Phospholipids Production Yarrowia lipolytica from Crude Glycerol

Phospholipids (PLs) are a class of lipids with many proven biological functions. They are commonly used in lipid replacement therapy to enrich cell membranes damaged in chronic neurodegenerative diseases, cancer, or aging processes. Due to their amphipathic nature, PLs have been widely used in food, cosmetic, and pharmaceutical products as natural emulsifiers and components of liposomes. In Yarrowia lipolytica, PLs are synthesized through a similar pathway like in higher eukaryotes. However, PL biosynthesis in this yeast is still poorly understood. The key intermediate in this pathway is phosphatidic acid, which in Y. lipolytica is mostly directed to the production of triacylglycerols and, in a lower amount, to PL. This study aimed to deliver a strain with improved PL production, with a particular emphasis on increased biosynthesis of phosphatidylcholine (PC). Several genetic modifications were performed: overexpression of genes from PL biosynthesis pathways as well as the deletion of genes responsible for PL degradation. The best performing strain (overexpressing CDP-diacylglycerol synthase (CDS) and phospholipid methyltransferase (OPI3)) reached 360% of PL improvement compared to the wild-type strain in glucose-based medium. With the substitution of glucose by glycerol, a preferred carbon source by Y. lipolytica, an almost 280% improvement of PL was obtained by transformant overexpressing CDS, OPI3, diacylglycerol kinase (DGK1), and glycerol kinase (GUT1) in comparison to the wild-type strain. To further increase the amount of PL, the optimization of culture conditions, followed by the upscaling to a 2 L bioreactor, were performed. Crude glycerol, being a cheap and renewable substrate, was used to reduce the costs of PL production. In this process 653.7 mg/L of PL, including 352.6 mg/L of PC, was obtained. This study proved that Y. lipolytica is an excellent potential producer of phospholipids, especially from waste substrates.     

Antioxidant properties of apple slices stored in starch-based films

The aim of this study was to evaluate the antioxidant properties of apple slices stored in edible starch films enriched with white and green tea extracts. All results were compared to that obtained for apple slices stored in polyethylene films. The use of starch films, as carrier of antioxidants, prolonged the storage life and improved quality of fresh-cut apples at the end of storage; however, deteriorated their lightness and increased their browning. Apple slices coated in starch films enriched with tea extracts exhibited higher antioxidant properties than those without these additives, as well as those in polyethylene films.