Molecular mechanisms and cellular functions of cGAS-STING signalling

The cGAS–STING signalling axis, comprising the synthase for the second messenger cyclic GMP–AMP (cGAS) and the cyclic GMP–AMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated by endogenous DNA, including extranuclear chromatin resulting from genotoxic stress and DNA released from mitochondria, placing cGAS–STING as an important axis in autoimmunity, sterile inflammatory responses and cellular senescence. Initial models assumed that co-localization of cGAS and DNA in the cytosol defines the specificity of the pathway for non-self, but recent work revealed that cGAS is also present in the nucleus and at the plasma membrane, and such subcellular compartmentalization was linked to signalling specificity of cGAS. Further confounding the simple view of cGAS–STING signalling as a response mechanism to infectious agents, both cGAS and STING were shown to have additional functions, independent of interferon response. These involve non-catalytic roles of cGAS in regulating DNA repair and signalling via STING to NF-κB and MAPK as well as STING-mediated induction of autophagy and lysosome- dependent cell death. We have also learnt that cGAS dimers can multimerize and undergo liquid–liquid phase separation to form biomolecular condensates that could importantly regulate cGAS activation. Here, we review the molecular mechanisms and cellular functions underlying cGAS–STING activation and signalling, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved

Role of Surface Carboxylates Deposition on the Deactivation of Fischer-Tropsch Synthesis Catalysts

Fischer-Tropsch synthesis (FTS) is a catalytic reaction, which involves the production of liquid hydrocarbon fuel from synthesis gas obtained from natural gas, biomass or coal via gasification and steam reforming. From an industrial perspective, both Co and Fe based catalysts have been applied. However, Co-based catalysts are preferred in FTS particularly for gas-to-liquid (GTL) processes as they have high activity, high selectivity to linear hydrocarbons and low activity for the unwanted water-gas shift reaction. However, Co-based catalysts are relatively expensive and deactivate in time. To make the FTS process economically more effective, a stable performance of the catalyst is required. Therefore, studying the catalyst deactivation is an important topic in the development of better industrial catalysts. Oxidation, sintering of active phase and deposition of oxygenated compounds are potential causes for deactivation. The possible role of oxygenates and their effect of catalyst deactivation, however, is less understood. With the aim to investigate the deposition of oxygenated compounds, particularly carboxylates, as hypothetical deactivation mechanism, operando characterisation techniques were adapted to monitor the chemical and physical properties and structure-activity relationship of the catalyst during the reaction. Operando Diffuse Reflectance Infrared Fourier Transform (DRIFT) and Mössbauer emission spectroscopy setups were employed that can be operated at industrially relevant FTS conditions.RST/Fundamental Aspects of Materials and Energ

Role of surface carboxylate deposition on the deactivation of cobalt on titania Fischer-Tropsch catalysts

Operando spectroscopic techniques (Diffusive Reflective Infrared Fourier-Transform and Mössbauer emission spectroscopy) were combined to investigate the role of oxygenates deposition on deactivation of cobalt on titania Fischer-Tropsch catalysts at high pressure. Clear formation of carboxylates was seen for catalysts prepared via both impregnation and precipitation, but more and heavier carboxylates were seen on the impregnated catalyst. This effect is related to a higher olefin content in the products obtained with the impregnated sample, resulting to increased formation of oxygenates through the hydroformylation side reaction. The combined gas chromatography/infrared spectroscopy data demonstrated that the surface carboxylate species are not involved in the catalyst deactivation, being most likely spectator species on the titania support.</p

Carbonation in Low-Temperature CO₂ Electrolyzers: Causes, Consequences, and Solutions

Electrochemical reduction of carbon dioxide (CO2) to useful products is an emerging power-to-X concept, which aims to produce chemicals and fuels with renewable electricity instead of fossil fuels. Depending on the catalyst, a range of chemicals can be produced from CO2 electrolysis at industrial-scale current densities, high Faraday efficiencies, and relatively low cell voltages. One of the main challenges for up-scaling the process is related to (bi)carbonate formation (carbonation), which is a consequence of performing the reaction in alkaline media to suppress the competing hydrogen evolution reaction. The parasitic reactions of CO2 with the alkaline electrolytes result in (bi)carbonate precipitation and flooding in gas diffusion electrodes, CO2 crossover to the anode, low carbon utilization efficiencies, electrolyte carbonation, pH-drift in time, and additional cost for CO2 and electrolyte recycling. We present a critical review of the causes, consequences, and possible solutions for the carbonation effect in CO2 electrolyzers. The mechanism of (bi)carbonate crossover in different cell configurations, its effect on the overall process design, and the economics of CO2 and electrolyte recovery are presented. The aim is to provide a better understanding of the (bi)carbonate problem and guide research directions to overcome the challenges related to low-temperature CO2 electrolysis in alkaline media.</p

Role of surface carboxylate deposition on the deactivation of cobalt on titania Fischer-Tropsch catalysts

Operando spectroscopic techniques (Diffusive Reflective Infrared Fourier-Transform and Mössbauer emission spectroscopy) were combined to investigate the role of oxygenates deposition on deactivation of cobalt on titania Fischer-Tropsch catalysts at high pressure. Clear formation of carboxylates was seen for catalysts prepared via both impregnation and precipitation, but more and heavier carboxylates were seen on the impregnated catalyst. This effect is related to a higher olefin content in the products obtained with the impregnated sample, resulting to increased formation of oxygenates through the hydroformylation side reaction. The combined gas chromatography/infrared spectroscopy data demonstrated that the surface carboxylate species are not involved in the catalyst deactivation, being most likely spectator species on the titania support.RST/Fundamental Aspects of Materials and EnergyEngineering ThermodynamicsInstrumenten groe

Beyond the limits: Pushing the boundaries of polyimide triboelectric nanogenerator performance at elevated temperatures

Beyond the limits: Pushing the boundaries of polyimide triboelectric nanogenerator performance at elevated temperature

Formulation and Evaluation of Gastroretentive Dosage Forms of Clarithromycin

The purpose of this research was to develop the hydrodynamically balanced delivery system of Clarithromycin (CLA) which, after oral administration should have the ability to prolong gastric residence time with the desired in vitro release profile for the localized action in the stomach, in the treatment of Helicobacter pylori (H.pylori) mediated peptic ulcer. By applying wet granulation technique floating tablets of Clarithromycin were prepared. The proportion of sodium bicarbonate was varied to get the least possible lag time, also the polymer part varied to get the desired release. In vivo radiographic studies were performed with Barium sulphate loaded formulation to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. The formulation developed using 66.2% Clarithromycin, 12% HPMC K4M polymer, 8% sodium bicarbonate gave floating lag time less than 3 min with a floating time of 12 h, and an in vitro release profile very near to the desired release. X-ray studies showed the enhanced gastric residence time of the tablet to 220 ± 30 min. The mechanism of release of Clarithromycin from the floating tablets is anomalous diffusion transport and follows zero order kinetics. In vivo radiographic studies suggest that the tablet has increased gastric residence time for the effective localized action of the antibiotic (Clarithromycin) in the treatment of H.pylori mediated peptic ulcer

Antibacterial CATH-2 Peptide Coating to Prevent Bone Implant-Related Infection

The development of antibacterial coatings is a promising approach to preventing biofilm formation and reducing the overuse of systemic antibiotics. However, widespread antibiotic use has resulted in antibiotic-resistant bacteria, limiting the efficacy of antibiotic-based coatings. Herein, an antibacterial coating is developed by layer-by-layer (LbL) assembly of two polymers namely PDLG (poly (D,L-lactide-co-glycolide)) and gelatin methacryloyl (GelMA) while chicken cathelicidin-2 (CATH-2), a cationic and amphipathic peptide, is loaded between these polymer layers. The electrospray method is used to apply the coatings to achieve efficient peptide loading and durability. The CATH-2 bactericidal concentration ranges are first identified, followed by a study of their cytotoxicity to human mesenchymal stem cells (hMSCs) and macrophage cell lines. Later, different LbL electrospray coating assemblies loaded with the optimal peptide concentration are sought. Various coating strategies are investigated to identify an LbL coating that exhibits prolonged and biocompatible CATH-2 release. The resulting CATH-2-coated titanium surfaces exhibit strong antibacterial activity against both Staphylococcus aureus and Escherichia coli bacteria for 4 days and are biocompatible with hMSCs and macrophage cells. This coating can be considered as a versatile delivery system platform for the delivery of CATH-2 peptides while avoiding cytotoxicity, particularly for the prevention of infections associated with implants.Team Peyman TaheriTeam Arjan Mo