Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants

As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C₆₀ fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene's hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously.     

Cavitation Erosion Resistance of Additively Manufactured Materials

Cavitation-induced wear, also known as cavitation erosion, can be found in many fluid power components, especially in water hydraulics. Cavitation erosion leads to component damage and might even cause system failure. The resistance of various materials to cavitation erosion when using conventional manufacturing processes has already been investigated in the past. In this work, the effects of additively manufactured materials on the resistance to cavitation erosion are investigated and compared to effects after conventional manufacturing. Also, the influence of the build-up direction of the additively manufactured specimens on cavitation erosion is determined. As the main indicators of cavitation erosion, mass loss and the surface structure are determined for all specimens.     

Elastohydrodynamic Simulation of Pneumatic Sealing Friction Considering 3D Surface Topography

This contribution presents an elastohydrodynamic lubrication (EHL) model for pneumatic spool valves. For an accurate estimation of the transient friction of this tribological sealing system, the surface topography of the cylindrical sealing counterfaces of the valve housings are measured and analyzed with an optical surface measurement instrument. Based on the surface topography data, tribological properties and flow factors of the system are derived. It has been found that the consideration of the surface topography has a significant influence on the simulation results of the EHL model, lowering the calculated friction force by up to 20 %.     

Engineered Platelet-Derived Growth Factor-Releasing Hydrogels Promote Fetal Membrane Healing In Vivo

Fetoscopic interventions to treat fetal anomalies are currently performed for a variety of conditions. Depending on the procedure, preterm rupture of the fetal membranes (FMs) happens in around 30% of the cases, potentially leading to preterm birth and fetal morbidity and mortality. Here, the capacity of modular transglutaminase crosslinked poly(ethylene glycol) (TG-PEG) hydrogels that release platelet-derived growth factor (PDGF)-BB to promote FM healing is described. In vitro, such growth factor-loaded hydrogels are able to stimulate amniotic cell migration and proliferation. When applied in vivo, these TG-PEG hydrogels tightly seal the FM and uterus defects created by a fetoscope and remain stable for 10 days. The migration of healing-related cells into such hydrogels in the myometrium, endometrium, and FM areas is only possible in soft TG-PEG hydrogels. Importantly, bioengineered hydrogels releasing PDGF-BB promote recruitment of host cells from the myometrium and the endometrium, and to a lesser extent from FM areas. In such hydrogels, the potent proliferation and matrix production of the recruited cells at the site of treatment into the biomaterial initiates a robust early healing response. PDGF-BB-loaded TG-PEG hydrogels hold great promise for the treatment of fetoscopy-induced FM defects and for the prevention of preterm birth.     

A vision of 14 T MR for fundamental and clinical science

Objective

We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set.

Research fields

The 14 Tesla system can be considered a ‘mesocope’: a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes.

Conclusions

The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR.

     

Myxococcus xanthus as Host for the Production of Benzoxazoles

Benzoxazoles are important structural motifs in pharmaceutical drugs. Here, we present the heterologous production of 3-hydroxyanthranilate-derived benzoxazoles in the host bacterium Myxococcus xanthus following the expression of two genes from the nataxazole biosynthetic gene cluster of Streptomyces sp. Tü 6176. The M. xanthus expression strain achieved a benzoxazole titer of 114.6±7.4 mg L⁻¹ upon precursor supplementation, which is superior to other bacterial production systems. Crosstalk between the heterologously expressed benzoxazole pathway and the endogenous myxochelin pathway led to the combinatorial biosynthesis of benzoxazoles featuring a 2,3-dihydroxybenzoic acid (2,3-DHBA) building block. Subsequent in vitro studies confirmed that this crosstalk is not only due to the availability of 2,3-DHBA in M. xanthus, rather, it is promoted by the adenylating enzyme MxcE from the myxochelin pathway, which contributes to the activation of aryl carboxylic acids and delivers them to benzoxazole biosynthesis.     

Nanoscale Control of the Surface Functionality of Polymeric 2D Materials

Typically, 2D nanosheets have a homogeneous surface, making them a major challenge to structure. This study proposes a novel concept of 2D organic nanosheets with a heterogeneously functionalized surface. This work achieves this by consecutively crystallizing two precisely synthesized polymers with different functional groups in the polymer backbone in a two-step process. First, the core platelet is formed and then the second polymer is crystallized around it. As a result, the central area of the platelets has a different surface functionality than the periphery. This concept offers two advantages: the resulting polymeric 2D platelets are stable in dispersion, which simplifies further processing and makes both crystal surfaces accessible for subsequent functionalization. Additionally, a wide variety of polymers can be used, making the process and the choice of surface functionalization very flexible.     

Dynamic Friction Model for the Investigation of Stick-Slip Oscillations

The optimization of lubricated sealing systems with respect to the stick-slip effect requires a friction model that describes the complex friction behavior in the lubricated contact area. This paper presents an efficient dynamic friction model based on the Stribeck curve, which allows to investigate the influencing parameters through finite element (FE) simulations. The simulation of a tribometer test using this friction model proofs that the model correlates well with the tribometer test results. It is shown that the system stiffness has a significant influence on the stick-slip tendency of the system.