Signaling of the receptor tyrosine kinase Axl and its ligand Gas6 is crucially involved in the development of liver fibrosis and hepatocellular carcinoma (HCC) by activation of hepatic stellate cells and modulation of hepatocyte differentiation. Shedding of Axl’s ectodomain leads to the release of soluble Axl (sAxl), which is increased in advanced fibrosis and in early-to-late stage HCC in the presence and absence of cirrhosis. Here, we focus on the dynamics of Axl receptor shedding and delineate possible scenarios how Axl signaling might act as driver of fibrosis progression and HCC development. Based on experimental and clinical data, we discuss the consequences of modifying Axl signaling by sAxl cleavage, as well as cellular strategies to escape from antagonizing effects of Axl shedding by the involvement of the hepatic microenvironment. We emphasize a correlation between free Gas6 and free sAxl levels favoring abundant Gas6/Axl signaling in advanced fibrosis and HCC. The raised scenario provides a solid basis for theranostics allowing the use of sAxl as an accurate diagnostic biomarker of liver cirrhosis and HCC, as well as Axl receptor signaling for therapeutic intervention in stratified HCC patients.

Lignocellulosic agricultural side products like wheat straw are widely seen as an important contribution to a sustainable future economy. However, the optimization of biorefinery processes, especially the pretreatment step, is crucial for an economically viable biorefinery. The monitoring of this pretreatment process in terms of delignification and the generation of the fermentation inhibitors acetic acid, furfural, and hydroxymethylfurfural (HMF) is essential in order to adapt the process parameters for a desired outcome and an economical operation. However, traditional wet chemistry methods are time-consuming and not suitable for on-line process monitoring. Therefore, UV-Vis spectroscopy in combination with partial least-squares regression was used for the determination of the concentrations of lignin, acetic acid, furfural, and HMF. Five different data blocks with increasing amounts of impurities were investigated to evaluate the influence of the inevitable impurities on the calibration models. Lignin showed a good prediction accuracy with 95% tolerance intervals between ±0.46 to ±1.6 mg/L for concentrations up to 30 mg/L. Also, the other components could be predicted with a sufficient accuracy for on-line process monitoring. A satisfactory calibration can be obtained with 10 to 20 reference samples valid at process temperatures between 160 • C and 180 • C.Lignin is a highly irregularly branched polyphenolic polyether, consisting of the primary monolignols, p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol, which are connected via aromatic and aliphatic ether bonds [6]. Even by using only one type of raw material in a lignocellulosic biorefinery, the growth environment, harvesting method, and storage can increase the inherent biomass property of heterogeneity [7].The mentioned variability in the composition and structure of feedstocks poses one of the most significant challenges to the industrial-scale processing of lignocellulosic materials [6]. Therefore, in-situ process monitoring of the pretreatment and the lignin concentration is essential for an adaption of process parameters and a constant product quality. However, traditional wet chemistry methods are expensive and time-consuming, requiring several days for a full composition analysis, which is a timeframe clearly incompatible with on-line process monitoring [8].In addition to the lignin concentration, degradation products generated during the pretreatment process such as furfural, hydroxymethylfurfural (HMF), and acetic acid are of interest. The furans originate from the dehydration of hexose and pentose sugars, whereas the acetic acid originates from the cleavage of the acetyl substitutions from xylan, and both are of particular importance for the toxicity in yeasts [9][10][11]. A low concentration of these inhibitors is therefore favored for subsequent fermentation processes and needs to be monitored. These components can be measured by HPLC in a time frame of hours, which is inappropriate for on-line process monitoring [12].Therefore, spec...