Different Molecular Forms of TFF3 in the Human Respiratory Tract: Heterodimerization with IgG Fc Binding Protein (FCGBP) and Proteolytic Cleavage in Bronchial Secretions

The polypeptide TFF3 belongs to the trefoil factor family (TFF) of lectins. TFF3 is typically secreted from mucous epithelia together with mucins. Both intestinal and salivary TFF3 mainly exist as disulfide-linked heterodimers with IgG Fc binding protein (FCGBP). Here, we investigated bronchial tissue specimens, bronchial secretions, and bronchoalveolar lavage (BAL) fluid from patients with a chronic obstructive pulmonary disease (COPD) background by fast protein liquid chromatography and proteomics. For the first time, we identified different molecular forms of TFF3 in the lung. The high-molecular mass form represents TFF3-FCGBP oligomers, whereas the low-molecular mass forms are homodimeric and monomeric TFF3 with possibly anti-apoptotic activities. In addition, disulfide-linked TFF3 heterodimers with an M_r of about 60k and 30k were detected in both bronchial secretions and BAL fluid. In these liquids, TFF3 is partly N-terminally truncated probably by neutrophil elastase cleavage. TFF3-FCGBP is likely involved in the mucosal innate immune defense against microbial infections. We discuss a hypothetical model how TFF3 might control FCGBP oligomerization. Furthermore, we did not find indications for interactions of TFF3-FCGBP with DMBT1gp³⁴⁰ or the mucin MUC5AC, glycoproteins involved in mucosal innate immunity. Surprisingly, bronchial MUC5AC appeared to be degraded when compared with gastric MUC5AC.     

The Discovery and Structure-Activity Evaluation of (+)-Floyocidin B and Synthetic Analogs

Tuberculosis represents one of the ten most common courses of death worldwide and the emergence of multidrug-resistant M. tuberculosis makes the discovery of novel anti-tuberculosis active structures an urgent priority. Here, we show that (+)-floyocidin B representing the first example of a novel dihydroisoquinoline class of fungus-derived natural products, displays promising antitubercular hit properties. (+)-Floyocidin B was identified by activity-guided extract screening and its structure was unambiguously determined by total synthesis. The absolute configuration was deduced from a key synthesis intermediate by single crystal X-ray diffraction analysis. A hit series was generated by the isolation of further natural congeners and the synthesis of analogs of (+)-floyocidin B. Extensive biological and physicochemical profiling of this series revealed first structure-activity relationships and set the basis for further optimization and development of this novel antitubercular scaffold.     

Dislocation-tuned electrical conductivity in solid electrolytes (9YSZ): A micro-mechanical approach

Tailoring the electrical conductivity of functional ceramics by introducing dislocations is a comparatively recent research focus, and its merits were demonstrated through mechanical means. Especially bulk deformation at high temperatures is suggested to be a promising method to introduce a high dislocation density. So far, however, controlling dislocation generation and their annihilation remains difficult. Although deforming ceramics generate dislocations on multiple length scales, dislocation annihilation at the same time appears to be the bottleneck to use the full potential of dislocations-tailoring the electrical conductivity. Here, we demonstrate the control over these aspects using a micromechanical approach on yttria-stabilized zirconia - YSZ. Targeted indentation well below the dislocation annihilation temperature resulted in extremely dense dislocation networks, visualized by chemical etching and electron channeling contrast imaging. Microcontact-impedance measurements helped evaluate the electrical response of operating individual slip systems. A significant conductivity enhancement is revealed in dislocation-rich regions compared to pristine ones in fully stabilized YSZ. This enhancement is mainly attributed to oxygen ionic conductivity. Thus, the possibility of increasing the conductivity is illustrated and provides a prospect to transfer the merits of dislocation-tuned electrical conductivity to solid oxygen electrolytes.     

Trichoderma-Derived Pentapeptides from the Infected Nest Mycobiome of the Subterranean Termite Coptotermes testaceus

Termites live in a dynamic environment where colony health is strongly influenced by surrounding microbes. However, little is known about the mycobiomes of lower termites and their nests, and how these change in response to disease. Here we compared the individual and nest mycobiomes of a healthy subterranean termite colony (Coptotermes testaceus) to one infected and ultimately eradicated by a fungal pathogen. We identified Trichoderma species in the materials of both nests, but they were also abundant in the infected termites. Methanolic extracts of Trichoderma sp. FHG000531, isolated from the infected nest, were screened for secondary metabolites by UHPLC-HR MS/MS-guided molecular networking. We identified many bioactive compounds with potential roles in the eradication of the infected colony, as well as a cluster of six unknown peptides. The novel peptide FE011 was isolated and characterized by NMR spectroscopy. The function of this novel peptide family as well as the role of Trichoderma species in dying termite colonies therefore requires further investigation.     

Hot Working Tool Steel with Bainitic Microstructure—The Mechanical Properties at Elevated Temperature

Usually, tool steels are used in quenched and tempered conditions. Due to the phase transition from austenite to martensite and the volume change during the transformation, controlling distortion might be challenging. A newly developed steel focusing on a bainitic structure, even for bigger dimensions, shows a lower hardness at ambient temperature than conventional hot working tool steels but with a lower temperature dependency. Therefore, at service temperature, the mechanical properties are comparable to established grades. Heat treatment is simplified by a simple austenitization and cooling process without special requirements on the cooling rate. Due to a generally lower cooling rate and lower hardness compared to a quench and tempering process, the risk of cracking is reduced while machinability is improved. With the combination of good weldability and rather low hardness after rapid cooling, this grade can also be processed in additive manufacturing and is well suited for a hybrid process of conventional and additive manufacturing.     

Techno-Economic Comparison of Bio-Cycling Processes for Mixed Plastic Waste Valorization

Mixed plastic waste is challenging for any recycling process. Here, an enzymatic recycling process is compared with a biotechnological upcycling process for valorizing mixed plastic waste constituted by PLA, PET, and PP. Both process routes are modeled in Aspen Plus, analyzed for bottlenecks, cost drivers, and sensitivity regarding enzymatic and microbial performance. While enzymatic recycling is only viable for uniform plastic feedstock, biotechnological upcycling operating at optimized process conditions reveals the potential to produce carbon-neutral succinic acid from mixed plastic waste.