Publikationen

TNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAIL^high CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis. Our work suggests that HG-induced TRAIL^high CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.

Pneumococcal infections represent a global health threat, which requires novel vaccine developments. Extracellular vesicles are secreted from most cells, including prokaryotes, and harbor virulence factors and antigens. Hence, bacterial membrane vesicles (MVs) may induce a protective immune response. For the first time, we formulate spray-dried gram-positive pneumococcal MVs-loaded vaccine microparticles using lactose/leucine as inert carriers to enhance their stability and delivery for pulmonary immunization. The optimized vaccine microparticles showed a mean particle size of 1–2 µm, corrugated surface, and nanocrystalline nature. Their aerodynamic diameter of 2.34 µm, average percentage emitted dose of 88.8%, and fine powder fraction 79.7%, demonstrated optimal flow properties for deep alveolar delivery using a next-generation impactor. Furthermore, confocal microscopy confirmed the successful encapsulation of pneumococcal MVs within the prepared microparticles. Human macrophage-like THP-1 cells displayed excellent viability, negligible cytotoxicity, and a rapid uptake around 60% of fluorescently labeled MVs after incubation with vaccine microparticles. Moreover, vaccine microparticles increased the release of pro-inflammatory cytokines tumor necrosis factor and interleukin-6 from primary human peripheral blood mononuclear cells. Vaccine microparticles exhibited excellent properties as promising vaccine candidates for pulmonary immunization and are optimal for further animal testing, scale-up and clinical translation.

Abstract Electrochemical ion separation is a promising technology to recover valuable ionic species from water. Pseudocapacitive materials, especially 2D materials, are up-and-coming electrodes for electrochemical ion separation. For implementation, it is essential to understand the interplay of the intrinsic preference of a specific ion (by charge/size), kinetic ion preference (by mobility), and crystal structure changes. Ti3C2Tz MXene is chosen here to investigate its selective behavior toward alkali and alkaline earth cations. Utilizing an online inductively coupled plasma system, it is found that Ti3C2Tz shows a time-dependent selectivity feature. In the early stage of charging (up to about 50 min), K+ is preferred, while ultimately Ca2+ and Mg2+ uptake dominate; this unique phenomenon is related to dehydration energy barriers and the ion exchange effect between divalent and monovalent cations. Given the wide variety of MXenes, this work opens the door to a new avenue where selective ion-separation with MXene can be further engineered and optimized.

Aqueous sodium-ion battery is a sustainable, non-toxic, non-flammable, and low-cost alternative to lithium-ion batteries, while transparency is a growing requisite of modern and integrated devices that batteries have yet to fulfill. In this work we present the preparation of a transparent and rechargeable aqueous Na-ion battery, assembled with different thin films of carbon/cobalt-based nanomaterials as electrodes. Cobalt-filled carbon nanotubes and cobalt/cobalt oxide encapsulated carbon nanoparticles are simultaneously synthesized in one single experimental procedure and deposited as thin and transparent films through the liquid/liquid interfacial route. The former is used for the electrosynthesis of a Prussian blue analogue, yielding carbon nanotubes/cobalt hexacyanoferrate thin film nanocomposite used as cathodes, while the cobalt/cobalt oxide/carbon nanoparticles thin film is used as the anode. The transparent device is prepared using a diluted aqueous solution of NaCl as the electrolyte, reaching capacities of 22 mAh•g−1 at 2 A•g−1 that remains stable after 2000 charge/discharge cycles, and energy density of 19.2 Wh•kg−1 at 1.4 kW•kg−1.

Octopus, clingfish, and larva use soft cups to attach to surfaces under water. Recently, various bioinspired cups have been engineered. However, the mechanisms of their attachment and detachment remain elusive. Using a novel microcup, fabricated by two-photon lithography, coupled with in situ pressure sensor and observation cameras, we reveal the detailed nature of its attachment/detachment under water. It involves elasticity-enhanced hydrodynamics generating “self-sealing” and high suction at the cup-substrate interface, converting water into “glue.” Detachment is mediated by seal breaking. Three distinct mechanisms of breaking are identified, including elastic buckling of the cup rim. A mathematical model describes the interplay between the attachment/detachment process, geometry, elasto-hydrodynamics, and cup retraction speed. If the speed is too slow, then the octopus cannot attach; if the tide is too gentle for the larva, then water cannot serve as a glue. The concept of “water glue” can innovate underwater transport and manufacturing strategies. Under-water soft cups form strong attachment with solid surfaces upon retraction by generating large transient suction.

Abstract Switchable micropatterned adhesives exhibit high potential as novel resource-efficient grippers in future pick-and-place systems. In contrast with the adhesion acting during the “pick” phase, the release during the “place” phase has received little research attention so far. For objects smaller than typically 1 mm, release may become difficult as gravitational and inertial forces are no longer sufficient to allow shedding of the object. A compressive overload can initiate release by elastic buckling of the fibrils, but the switching ratio (ratio between high and low adhesion force) is typically only 2–3. In this work, new microfibrillar designs are reported exhibiting directional buckling with high switching ratios in the order of 20. Their functionality is illustrated by in situ optical observation of the contact signatures. Such micropatterns can enable the successful release of small objects with high placement accuracy.

Crack growth in viscoelastic materials is understood with the use of cohesive models, or steady state theories which focus on viscoelastic dissipation. We consider a double cantilever beam (DCB) specimen under a remote constant pure moment, which is initially suddenly applied to the beams. It is shown that the response to the applied moment rapidly reaches a steady state in terms of crack propagation speed. In contrast, it is shown that the external work rate, contributing to fracture energy, stored elastic energy and viscous dissipation, has a transient that possibly lasts a significantly longer time. The dissipation rate increases with speed for a standard material, reaching a limit governed by the ratio of instantaneous to relaxed modulus. However, the initial dissipation rate at low crack propagation speeds can be orders of magnitude larger than the latter limit, and depends on the ratio between the initial crack size and the fracture process zone size, a regime which we define ultratough. For thin beams, we do not find any evidence, even in the steady state, of the dissipation-based theories’ suggestion of a reduced maximum load and then of an unstable regime of decreasing load with speed.

Observing processes of nanoscale materials of low atomic number is possible using liquid phase electron microscopy (LP-EM). However, the achievable spatial resolution (d) is limited by radiation damage. Here, we examine a strategy for optimizing LP-EM experiments based on an analytical model and experimental measurements, and develop a method for quantifying image quality at ultra low electron dose De using scanning transmission electron microscopy (STEM). As experimental test case we study the formation of a colloidal binary system containing 30-nm diameter SiO2 nanoparticles (SiONPs), and 100-nm diameter polystyrene microspheres (PMs). We show that annular dark field (DF) STEM is preferred over bright field (BF) STEM for practical reasons. Precise knowledge of the material's density is crucial for the calculations in order to match experimental data. To calculate the detectability of nano-objects in an image, the Rose criterion for single pixels is expanded to a model of the signal to noise ratio obtained for multiple pixels spanning the image of an object. Using optimized settings, it is possible to visualize the radiation-sensitive, hierarchical low-Z binary structures, and identify both components.

Syntheses of N-heterocyclic compounds that permit a flexible introduction of various substitution patterns using inexpensive and diversely available starting materials are highly desirable. Easy to handle and reusable catalysts based on earth-abundant metals are especially attractive for these syntheses. We report here on the synthesis of 3,4-dihydro-2H-pyrroles via the hydrogenation and cyclization of nitro ketones. The latter are easily accessible from three components: a ketone, an aldehyde and a nitroalkane. Our reaction has a broad scope and 23 of the 33 products synthesized are compounds which have not yet been reported. The key to the general hydrogenation/cyclization reaction is a highly active, selective and reusable nickel catalyst, which was identified from a library of 24 earth-abundant metal catalysts.

Three Schiff bases of tranexamic acid were successfully synthesized by a mechanochemical green method, which is 4-{(5-bromo-2- hydroxybenzylidene)amino]methyl}cyclohexanecarboxylic acid (SB1), 4-{(2-hydroxybenzylidene)amino]methyl}cyclohexanecarboxylic acid (SB2), and 4-{(4-nitrobenzylidene)amino]methyl}cyclohexanecarboxylic acid (SB3) in good yield. Their structures were confirmed based on spectroscopic data. The bases displayed considerable urease inhibitory activity with IC50 (µg/mL) 33.41, 40.64, 26.18, and 11.14 for SB1, SB2, SB3, and standard thiourea, respectively. They revealed weak antiradical activity in DPPH assay with EC50 (µg/mL) 1138, 1239, and 24248 for SB1, SB2, and SB3, respectively. In conclusion, grinding is an efficient and environmentally friendly method for synthesizing these bases, which may provide potential candidates for new medicines.