Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids 1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols 3,4. Ferroptosis has been implicated in the cell death that underlies several degenerative conditions 2 , and induction of ferroptosis by inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death 5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines 6 , suggesting that additional factors govern resistance to ferroptosis. Here, employing a synthetic lethal CRISPR/Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

A substantial body of literature has provided evidence for the role of gut microbiota in metabolic diseases including type 2 diabetes. However, reports vary regarding the association of particular taxonomic groups with disease. In this systematic review, we focused on the potential role of different bacterial taxa affecting diabetes. We have summarized evidence from 42 human studies reporting microbial associations with disease, and have identified supporting preclinical studies or clinical trials using treatments with probiotics. Among the commonly reported findings, the genera of Bifidobacterium, Bacteroides, Faecalibacterium, Akkermansia and Roseburia were negatively associated with T2D, while the genera of Ruminococcus, Fusobacterium, and Blautia were positively associated with T2D. We also discussed potential molecular mechanisms of microbiota effects in the onset and progression of T2D.

The molecular understanding of autophagy has originated almost exclusively from yeast genetic studies. Little is known about essential autophagy components specific to higher eukaryotes. Here we perform genetic screens in C. elegans and identify four metazoan-specific autophagy genes, named epg-2, -3, -4, and -5. Genetic analysis reveals that epg-2, -3, -4, and -5 define discrete genetic steps of the autophagy pathway. epg-2 encodes a coiled-coil protein that functions in specific autophagic cargo recognition. Mammalian homologs of EPG-3/VMP1, EPG-4/EI24, and EPG-5/mEPG5 are essential for starvation-induced autophagy. VMP1 regulates autophagosome formation by controlling the duration of omegasomes. EI24 and mEPG5 are required for formation of degradative autolysosomes. This study establishes C. elegans as a multicellular genetic model to delineate the autophagy pathway and provides mechanistic insights into the metazoan-specific autophagic process.

We describe the development of novel and biocompatible core/shell (α-NaYbF4:Tm3+)/CaF2 nanoparticles which exhibit highly efficient NIRin-NIRout upconversion (UC) for high contrast and deep bioimaging. When excited at ~980 nm, these nanoparticles emit photoluminescence (PL) peaked at ~800 nm. The quantum yield of this UC PL under low power density excitation (~0.3 W/cm2) is 0.6±0.1%. This high UC PL efficiency is realized by suppressing surface quenching effects via hetero-epitaxial growth of a biocompatible CaF2 shell which results in a 35-fold increase in the intensity of UC PL from the core. Small animal whole-body UC PL imaging with exceptional contrast (signal-to-background ratio of 310) is shown using BALB/c mice intravenously injected with aqueously dispersed nanoparticles (700 pmol/kg). High-contrast UC PL imaging of deep tissues is also demonstrated, using a nanoparticle-loaded synthetic fibrous mesh wrapped around rat femoral bone, and a cuvette with nanoparticle aqueous dispersion - covered with a 3.2-cm thick animal tissue (pork).

A novel high excited state energy transfer pathway to overcome the phonon quenching effect in rare-earth (RE) oxide upconversion (UC) materials is reported. In Er(Tm)-Yb oxide systems, an extraordinary enhancement of UC luminescence efficiency with four orders of magnitude is realized by Mo co-doping. The RE oxides with significant UC efficiency are successfully utilized for temperature sensing and in vivo imaging.