System xc− was recently described as the most upstream node in a novel form of regulated necrotic cell death, called ferroptosis. In this context, the small molecule erastin was reported to target and inhibit system xc−, leading to cysteine starvation, glutathione depletion and consequently ferroptotic cell death. Although the inhibitory effect of erastin towards system xc− is well-documented, nothing is known about its mechanism of action. Therefore, we sought to interrogate in more detail the underlying mechanism of erastin’s pro-ferroptotic effects. When comparing with some well-known inhibitors of system xc−, erastin was the most efficient inhibitor acting at low micromolar concentrations. Notably, only a very short exposure of cells with low erastin concentrations was sufficient to cause a strong and persistent inhibition of system xc−, causing glutathione depletion. These inhibitory effects towards system xc− did not involve cysteine modifications of the transporter. More importantly, short exposure of tumor cells with erastin strongly potentiated the cytotoxic effects of cisplatin to efficiently eradicate tumor cells. Hence, our data suggests that only a very short pre-treatment of erastin suffices to synergize with cisplatin to efficiently induce cancer cell death, findings that might guide us in the design of novel cancer treatment paradigms.

Cellulose valerate (CV)/poly(e-caprolactone) (PCL) blends were investigated to clarify the effect of the degree of substitution (DS) of the cellulose ester component on the miscibility. CVs of DS > 2.15 were miscible with PCL in their amorphous states, as judged from the detection of a single T g by differential scanning calorimetry (DSC). This result and other complementary data for cellulose acetate (CA), propionate (CP), and butyrate (CB) blends with PCL made up a miscibility map as a function of the number N of carbons in the normal acyl substituent as well as of DS. CB of N = 4 and CV of N = 5, the ester side-chains of which make a higher similarity in chemical structure with a repeating unit of PCL, were found to be miscible with the aliphatic polyester at a comparatively lower DS; the critical butyryl DS of *1.85 being still lower than 2.15. For PCL-rich compositions of CB(DS > 2.0)/PCL and CV(DS > 2.2)/PCL blends, isothermal melt-crystallization behaviour was characterized by calorimetry and polarized optical microscopy. The CB and CV components gave rise to a marked diminution of the crystallization rate of PCL, as a result of the diluent action of the cellulose esters in the respective miscible, molten mixtures. Through a quantitative analysis of the kinetics, it is suggested regarding the supramolecular morphology that the bulky cellulose esters would be trapped not only on the fold surfaces but also on the growth faces of PCL lamellar crystals, to form a non-crystalline mixed polymer phase in the crystal boundary regions. Keywords Cellulose alkyl ester Á Poly(e-caprolactone) Á Polymer blends Á Miscibility Á Crystallization behaviour Abbreviations CA Cellulose acetate CAV Cellulose acetate valerate CB Cellulose butyrate CBV Cellulose butyrate valerate CC Cellulose caproate CE Cellulose enanthate CP Cellulose propionate CPV Cellulose propionate valerate CV Cellulose valerate DS

Graft copolymers of CA and CB with PCL were prepared at compositions rich in PCL. Kinetic DSC data were analyzed in terms of a folded‐chain crystallization formula expanded for a binary mixing system of amorphous/crystalline polymers. The order of crystallization rates was plain PCL > CA‐g‐PCL (DS = 2.98) > CB‐g‐PCL (DS = 2.1–2.95) > CA‐g‐PCL (DS = 2.1–2.5), and the fold‐surface free energy of the PCL crystals obeyed the reverse order. POM revealed a generally tardy growth of spherulites for all the graft copolymers. The slower crystallization process may be ascribed primarily to the compulsory effect of anchoring PCL chains onto the semi‐rigid cellulose backbone. Intercomponent miscibility of the CA/PCL and CB/PCL pairs was also taken into consideration.

The cystine/glutamate antiporter, system x c − , is essential for the efficient uptake of cystine into cells. Interest in the mechanisms of system x c − function soared with the recognition that system x c − presents the most upstream node of ferroptosis, a recently described form of regulated necrosis relevant for degenerative diseases and cancer. Since targeting system x c − hold the great potential to efficiently combat tumor growth and metastasis of certain tumors, we disrupted the substrate-specific subunit of system x c − , xCT (SLC7A11) in the highly metastatic mouse B16F10 melanoma cell line and assessed the impact on tumor growth and metastasis. Subcutaneous injection of tumor cells into the syngeneic B16F10 mouse melanoma model uncovered a marked decrease in the tumor-forming ability and growth of KO cells compared to control cell lines. Strikingly, the metastatic potential of KO cells was markedly reduced as shown in several in vivo models of experimental and spontaneous metastasis. Accordingly, survival rates of KO tumor-bearing mice were significantly prolonged in contrast to those transplanted with control cells. Analyzing the in vitro ability of KO and control B16F10 cells in terms

A N-acetylated chitosan hydrogel was investigated for ocular applications. One of the drawbacks in the original hydrogel protocol, poor moldability, was circumvented by optimizing the addition of the acetylating agent, acetic acid anhydride (Ac 2 O), at −10 °C. This simple but significant optimization realized the preparation of N-acetylated chitosan hydrogels with a wider variety of parameters such as higher chitosan concentration and molecular weight, the use of a more benign solvent (ethanol replaced methanol), and the arbitral shapes ranging from microbeads and contact lenses to bulky blocks that could be gripped. The prepared N-acetylated chitosan hydrogels exhibited high transparency and integrity given the nanofibrous network made of highly crystalline α-chitin. Furthermore, the gel retained a regenerable character: an oven-dried gel was reswollen by emersion in an acid bath. These previously unnoticed advantages and the innate high biocompatibility of chitosan and chitin elevate N-acetylated chitosan hydrogel as a next-generation bio-derived soft material for ocular applications such as contact lenses, artificial corneas, and drug delivery vehicles.