Autophagy, a lysosomal degradation pathway, plays an essential role in multiple aspects of immunity, including immune system development, regulation of innate and adaptive immune and inflammatory responses, selective degradation of intracellular microbes, and host protection against infectious diseases 1 , 2 . Unlike autophagy induction by stimuli such as nutrient deprivation and mTOR suppression, little is known about how autophagosomal biogenesis is initiated in mammalian cells in response to viral infection. We performed genome-wide siRNA screens and found that the endosomal protein sorting nexin 5 (SNX5) 3 , 4 is essential for virus-induced, but not for basal, stress- or endosome-induced, autophagy. We showed that SNX5 deletion increases cellular susceptibility to viral infection in vitro , and that Snx5 knockout in mice enhances lethality after infection with multiple human viruses. Mechanistically, SNX5 interacts with beclin 1 and ATG14-containing Class III phosphatidylinositol 3-kinase (PI3KC3) complex 1 (PI3KC3-C1), increases the lipid kinase activity of purified PI3KC3-C1, and is required for endosomal generation of PI3P and recruitment of the PI3P-binding protein WIPI2 to virion-containing endosomes. These findings identify a context- and organelle-specific mechanism – SNX5-dependent PI3KC3-C1 activation at endosomes – for autophagy initiation during viral infection.

In response to starvation, cells undergo increased levels of autophagy and cell cycle arrest but the role of autophagy in starvation-induced cell cycle arrest is not fully understood. Here we show that autophagy genes regulate cell cycle arrest in the budding yeast Saccharomyces cerevisiae during nitrogen starvation. While exponentially growing wild-type yeasts preferentially arrest in G1/G0 in response to starvation, yeasts carrying null mutations in autophagy genes show a significantly higher percentage of cells in G2/M. In these autophagy-deficient yeast strains, starvation elicits physiological properties associated with quiescence, such as Snf1 activation, glycogen and trehalose accumulation as well as heat-shock resistance. However, while nutrient-starved wild-type yeasts finish the G2/M transition and arrest in G1/G0, autophagy-deficient yeasts arrest in telophase. Our results suggest that autophagy is crucial for mitotic exit during starvation and appropriate entry into a G1/G0 quiescent state.

Progesterone is often used to protect the endometrium and prevent endometrial cancer. An intensive study on its molecular mechanism in endometrial cancer would contribute to the development of more promising therapies. Relevant lncRNAs and mRNAs expression data in endometrial cancer cell line Ishikawa pretreated and post‐treated with progesterone were derived from Gene Expression Omnibus (accession no. GSE29435), and then we analyzed long noncoding RNAs and mRNAs with differential expressions in two different conditions. The Cytoscape software, TargetScan, miRanda, and Human microRNA Disease Database (HMDD) websites were employed. Gene set enrichment analysis (GSEA) was used to determine related Kyoto Encyclopedia of Genes and Genomes pathways alteration in Ishikawa cells treated with progesterone. In addition to bioinformatics analysis, Reverse Transcription‐Polymerase Chain Reaction (RT‐PCR), Western blot, and dual‐luciferase reporter assays were performed. The impact of progesterone on cell propagation and cell cycle was testified by colony formation and flow cytometry analysis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was the most significantly downregulated lncRNA in endometrial cancer cells treated with progesterone. Lymphoid enhancing factor 1 (LEF1) was positively associated with NEAT1, and eventually hsa_miR‐146b‐5p was validated to target both LEF1 and NEAT1. Wnt/β‐catenin signaling pathway was identified to involve in endometrial cancer. NEAT1 or LEF1 was overexpressed in endometrial cancer cells while downregulated following post‐treatment with progesterone. Conversely, miR‐146b‐5p was notably decreased in Ishikawa cells while upregulated after treatment with progesterone. Downstream gene c‐myc or MMP9 regulated by upstream gene LEF1 in Wnt/β‐catenin signaling pathway was remarkably increased in Ishikawa cells and positively related with NEAT1. Progesterone inhibited cell cycle and viability through regulating NEAT1/miR‐146b‐5p axis via Wnt/β‐catenin signaling pathway. Progesterone exerted suppressive influence on endometrial cancer progression via regulation of lncRNA NEAT1/miR‐146b‐5p‐mediated Wnt/β‐catenin signaling pathway, which might reveal new strategies for developing more effective therapeutics. © 2018 IUBMB Life, 71(1):223–234, 2019

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide, and both cardiac necroptosis and endoplasmic reticulum stress (ERS) have been involved in the pathophysiology of AMI. ZYZ-803 is a hybrid molecule of a dual donor for gasotransmitters H2S and NO. The aim of the present study is to investigate the antinecroptosis role and potential mechanisms of ZYZ-803 in the setting of ERS during AMI injury. In vivo, ZYZ-803 preserves cardiac function and reduces infarct size significantly after 24-hour left coronary artery ligation through revising H2S and NO imbalance. In addition, ZYZ-803 relieves ERS and necroptosis in an AMI heart. In vitro, ZYZ-803 ameliorates ERS-related necroptosis induced by tunicamycin, and such effect has been depending on the receptor-interacting protein 3- (RIP3-) Ca2+-calmodulin-dependent protein kinase (CaMKII) signaling pathway. These findings have identified a novel antinecroptosis potential of ZYZ-803, providing a valuable candidate for cardioprotection in acute myocardial ischemia.

Cr 3+ , Eu 2+ , and Dy 3+ codoped Sr 4 Al 14 O 25 has been synthesized by solid-state reaction. Long persistent phosphorescence in red of Cr 3+ and in blue of Eu 2+ has been observed in this system with persistence times of over 2 h for the red and 10 h for the blue. Red phosphorescence is performed through persistent energy transfer from Eu 2+ to Cr 3+ , converting the blue to the red. Concentration effect is analyzed based on energy transfer. The calculated results are in good agreement with the experimental data. The different decay patterns of the red and blue phosphorescence are measured and discussed.