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Summary: Background: Matrix metalloproteinases (MMPs) are implied in blood–brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). Methods: We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. Findings: Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40–94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4–569.6] vs 441 [IQR 223.4–731.5] ng/ml, p

The use of lactic acid bacteria as a low-cost sustainable management tool to prevent further build-up of Fusarium mycotoxins during grain storage is increasingly propagated. It has been reported that even deoxynivalenol contamination already formed in the field can be reduced by such treatment in unknown ways. An enigmatic deoxynivalenol derivative, 3-lactyl-deoxynivalenol, has been reported already in 1982 as the toxic principle of Fusarium-infected barley from China, but very little is known about this metabolite. Here, we show that the enzymatic machinery of Fusarium graminearum is sufficient for its biosynthesis. Similarly, when challenged with propionic acid, F. graminearum can form a novel modified mycotoxin, 3-propionyl-deoxynivalenol. Lactic acid and propionic acid are first converted into lactyl-CoA and propionyl-CoA, respectively. These acyl-CoA derivatives can subsequently be used by the 3-O-acyltransferase encoded by TRI101. We expressed the respective genes in E. coli and utilized the affinity-purified proteins for enzymatic synthesis of the reference substances 3-lactyl- and 3-propionyl-deoxynivalenol. The structures of the purified compounds were confirmed by nuclear magnetic resonance spectroscopy. Preliminary toxicological assessment using in vitro translation assays indicated residual toxicity, most likely due to reactivation of deoxynivalenol by de-acylation. In conclusion, this study reports a method to synthesize 3-lactyl- and 3-propionyl-deoxynivalenol reference substances, which will be highly useful to determine occurrences of these acylated deoxynivalenol-derivatives in cereal samples and to perform more detailed studies to evaluate their toxicological relevance.