Cell‐Instructive Multiphasic Gel‐in‐Gel Materials

Developing tissue is typically soft, highly hydrated, dynamic, and increasingly heterogeneous matter. Recapitulating such characteristics in engineered cell‐instructive materials holds the promise of maximizing the options to direct tissue formation. Accordingly, progress in the design of multiphasic hydrogel materials is expected to expand the therapeutic capabilities of tissue engineering approaches and the relevance of human 3D in vitro tissue and disease models. Recently pioneered methodologies allow for the creation of multiphasic hydrogel systems suitable to template and guide the dynamic formation of tissue‐ and organ‐specific structures across scales, in vitro and in vivo. The related approaches include the assembly of distinct gel phases, the embedding of gels in other gel materials and the patterning of preformed gel materials. Herein, the capabilities and limitations of the respective methods are summarized and discussed and their potential is highlighted with some selected examples of the recent literature. As the modularity of the related methodologies facilitates combinatorial and individualized solutions, it is envisioned that multiphasic gel‐in‐gel materials will become a versatile morphogenetic toolbox expanding the scope and the power of bioengineering technologies.     

Genetically Programmed Regioselective Immobilization of Enzymes in Biosilica Microparticles

Diatoms are single‐celled microalgae that produce a large variety of hierarchically porous, silica‐based microparticles as cell wall material. The presence of genetically encoded silica nanopatterns endows the biosilica with favorable properties for a wide range of applications including catalysis, chemical sensing, photonics, and drug delivery. Enhancing the performance of diatom biosilica requires i) a better understanding of the structure–property relationship in this material, and ii) methods that enable the manipulation of the biosilica structure and properties in a targeted manner. Here, genetic engineering of the diatom Thalassiosira pseudonana is employed to immobilize enzymes (glucose oxidase and horseradish peroxidase) into structurally distinct regions of the biosilica, which are termed valves and girdle bands. Remarkably, glucose oxidase in girdle bands exhibits >3‐fold higher catalytic activities compared to its location in valves. It is demonstrated through enzyme accessibility studies, protein engineering, and genetic engineering of biosilica morphology that the divergent enzyme activities are caused by the differences in the inherent silica nanopatterns of valves and girdle bands. This work highlights the importance of silica nanoscale architecture for the activity of immobilized enzymes and provides unprecedented tools for the biotechnological production of silica microparticles with tailored catalytic activities and anisotropic functionalities.     

A Murine Oral‐Exposure Model for Nano‐ and Micro‐Particulates: Demonstrating Human Relevance with Food‐Grade Titanium Dioxide

Human exposure to persistent, nonbiological nanoparticles and microparticles via the oral route is continuous and large scale (10¹²–10¹³ particles per day per adult in Europe). Whether this matters or not is unknown but confirmed health risks with airborne particle exposure warns against complacency. Murine models of oral exposure will help to identify risk but, to date, lack validation or relevance to humans. This work addresses that gap. It reports i) on a murine diet, modified with differing concentrations of the common dietary particle, food grade titanium dioxide (fgTiO₂), an additive of polydisperse form that contains micro‐ and nano‐particles, ii) that these diets deliver particles to basal cells of intestinal lymphoid follicles, exactly as is reported as a “normal occurrence” in humans, iii) that confocal reflectance microscopy is the method of analytical choice to determine this, and iv) that food intake, weight gain, and Peyer's patch immune cell profiles, up to 18 weeks of feeding, do not differ between fgTiO₂‐fed groups or controls. These findings afford a human‐relevant and validated oral dosing protocol for fgTiO₂ risk assessment as well as provide a generalized platform for application to oral exposure studies with nano‐ and micro‐particles.     

Editorial: Industrial relevance of molybdenum in China

About 80% of all molybdenum mined in the world (not including units recovered via recycling) is used as an alloying element in iron and steel. In general, the intensity of molybdenum use in China is still lower than in more highly developed regions such as the USA and Europe. This difference is manifest in both carbon steels and stainless steels, suggesting a significant opportunity for more widespread use of molybdenum in the future as China follows its self-reliance policy, calling for more sophisticated materials. Active market development, as being pursued by the International Molybdenum Association (IMOA), is a key asset in that respect. This article summarizes some key facts on molybdenum mining, use and market development in China.The full text can be downloaded at https://link.springer.com/content/pdf/10.1007%2Fs40436-019-00270-5.pdf     

Design Principles of Ionic Liquids for Transdermal Drug Delivery

Ionic liquids (ILs) and deep eutectic solvents have shown great promise in drug delivery applications. Choline‐based ILs, in particular choline and geranic acid (CAGE), have been used to enhance the transdermal delivery of several small and large molecules. However, detailed studies outlining the design principles of ILs for transdermal drug delivery are still lacking. Using two model drugs of differing hydrophilicities, acarbose and ruxolitinib and 16 ILs, the dependence of skin penetration on the chemical properties of ILs is examined. First, the impact of ion stoichiometry on skin penetration of drugs is assessed using CAGE, which evidences that a molar ratio of 1:2 of choline to geranic acid yields the highest delivery. Subsequently, variants of CAGE are prepared using anions with structural similarity to geranic acid and cations with structural similarity to choline at a ratio of 1:2. Mechanistic studies reveal that the potency of ILs in enhancing transdermal drug delivery correlates inversely with the inter‐ionic interactions as determined by 2D NMR spectroscopy. Using this understanding, a new IL is designed, and it provides the highest delivery of ruxolitinib of all ILs tested here. Overall, these studies provide a generalized framework for optimizing ILs for enhancing skin permeability.     

Non-technical communication factors at the Vessel Traffic Services

This study done at the Vessel Traffic Services (VTS) explored how the VTS operators (VTSOs) communicated with ships and other actors in the maritime sociotechnical system and how decisions were made with regard to assisting traffic in maintaining safe passage in port areas, where most vessel movements are seen and accidents occur. The fieldwork was done during four independent visits to a VTS centre under the Swedish Maritime Authority, with a total sample of six VTSOs and one VTS instructor. The qualitative data were sorted and coded using a grounded theory approach. The data pointed at non-technical information processing and communication factors that play a role in decision-making and ultimately in safety. During protocol operations at the VTS, these factors influenced how VTSOs judged the skills of the vessels’ bridge teams, and how they approached them. This is a time where much effort is being put into upgrading technological systems, and these will have the power to change the ways in which the maritime network obtains and processes information, as well as how they can communicate with each other. The further development of technological systems, work protocols and training programmes can benefit from taking the soft aspects of communication and the needs of the operators and their tasks into account for the enhancement of safety.     

Measurement of Onset of Structural Relaxation in Melt-Quenched Phase Change Materials

Chalcogenide phase change materials enable non-volatile, low-latency storage-class memory. They are also being explored for new forms of computing such as neuromorphic and in-memory computing. A key challenge, however, is the temporal drift in the electrical resistance of the amorphous states that encode data. Drift, caused by the spontaneous structural relaxation of the newly recreated melt-quenched amorphous phase, has consistently been observed to have a logarithmic dependence in time. Here, it is shown that this observation is valid only in a certain observable timescale. Using threshold-switching voltage as the measured variable, based on temperature-dependent and short timescale electrical characterization, the onset of drift is experimentally measured. This additional feature of the structural relaxation dynamics serves as a new benchmark to appraise the different classical models to explain drift.     

The Role of Selectively Located Commercial Graphene Nanoplatelets in the Electrical Properties,Morphology, and Stability of EVA/LLDPE Blends

Graphene nanoplatelets (GN) produced on a large scale by mechanochemical exfoliation of graphite are incorporated in a co‐continuous ethylene‐vinyl acetate/linear low‐density polyethylene (EVA/LLDPE) blend. Two different processing routes are chosen to selectively place GN in the EVA phase or force its migration to the EVA/LLDPE interface. The results show a drastic decrease in the electrical percolation threshold when the blends are compared to the respective single‐polymer composites. Even with the presence of agglomerates, GN particles are able to migrate to the blend interface and stabilize the morphology and hence the electrical properties. Annealing the insulating samples at processing temperatures causes a drastic increase in conductivity due to continued GN migration and blend morphology coarsening. Semi‐conductive samples, in which a more robust GN network is already established during processing, present no change in morphology but a slight increase in conductivity during annealing. The mechanical performance of the materials is also evaluated and some of the blends with GN present similar elongation at break as pure EVA, but with increased tensile modulus and tensile strength. The electrical performance at different working temperatures shows that the EVA/LLDPE/GN composites are good candidates to act as a semi‐conductive screen material in power cables or as anti‐static materials in electronic devices.     

Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells

Human proteinase‐activated receptor 2 (PAR2), a transmembrane G‐protein‐coupled receptor (GPCR), is an attractive target for a novel anticancer therapy, as it plays a critical role in cell migration and invasion. Selective PAR2 inhibitors therefore have potential as anti‐metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure–activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target, protein kinase C (PKC). For this purpose, an efficient gram‐scale total synthesis of indolactam V (i.e., the parent structure of all teleocidins) was developed, and a library of derivatives was prepared. Some compounds were indeed found to exhibit high potency as PAR2 inhibitors at low nanomolar concentrations with improved selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the C3 and C4 positions of the indole core proved to be essential for target binding, whereas activity and target selectivity depends on the substituents at N1 or C7. This study revealed novel derivatives that show high efficacy in PAR2 antagonism combined with increased selectivity.