In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.Antifreeze proteins (AFPs) can inhibit the freezing of body fluid at subzero temperatures to promote the survival of various organisms living in polar regions. Type III AFPs are categorized into three subgroups, QAE1, QAE2, and SP isoforms, based on differences in their isoelectric points. We determined the thermal hysteresis (TH), ice recrystallization inhibition (IRI), and cryopreservation activity of three isoforms of the notched-fin eelpout AFP and their mutant constructs and characterized their structural and dynamic features using NMR. The QAE1 isoform is the most active among the three classes of III AFP isoforms, and the mutants of inactive QAE2 and SP isoforms, QAE2ACT and SPACT, displayed the full TH and IRI activities with resepect to QAE1 isoform. Cryopreservation studies using mouse ovarian tissue revealed that the QAE1 isoform and the active mutants, QAE2ACT and SPACT, more effectively preserved intact follicle morphology and prevented DNA double-strand break damage more efficiently than the inactive isoforms. It was also found that all active AFPs, QAE1, QAE2ACT, and SPACT, formed unique H-bonds with the first 310 helix, an interaction that plays an important role in the formation of anchored clathrate water networks for efficient binding to the primary prism and pyramidal planes of ice crystals, which was disrupted in the inactive isoforms. Our studies provide valuable insights into the molecular mechanism of the TH and IRI activity, as well as the cryopreservation efficiency, of type III AFPs.Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on Mucor and Rhizopus. Selleck SNDX-5613 This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic modification of the outer spore wall of Lichtheimia corymbifera, one of the major causative agents of mucormycosis. Episporic modifications were performed and their consequences on phagocytosis, intracellular survival and virulence by murine alveolar macrophages and in an invertebrate infection model were elucidated. While depletion of lipids did not affect the phagocytosis of both strains, delipidation led to attenuation of LCA strain but appears to be dispensable for infection with LCV strain in the settings used in this study. Combined glucano-proteolytic treatment was necessary to achieve a significant decrease of virulence of the LCV strain in Galleria mellonella during maintenance of the full potential for spore germination as shown by a novel automated germination assay. Proteolytic and glucanolytic treatments largely increased phagocytosis compared to alive resting and swollen spores. Whilst resting spores barely (1-2%) fuse to lysosomes after invagination in to phagosomes, spore trypsinization led to a 10-fold increase of phagolysosomal fusion as measured by intracellular acidification. This is the first report of a polyphasic measurement of the consequences of episporic modification of a mucormycotic pathogen in spore germination, spore surface ultrastructure, phagocytosis, stimulation of Toll-like receptors (TLRs), phagolysosomal fusion and intracellular acidification, apoptosis, generation of reactive oxygen species (ROS) and virulence.An extracellular lipase from Amycolatopsis mediteranei (AML) with potential applications in process biotechnology was recently cloned and examined in this laboratory. In the present study, the 3D structure of AML was elucidated by comparative modelling. AML lacked the ‚lid‘ structure observed in most true lipases and shared similarities with plastic degrading enzymes. Modelling and substrate specificity studies showed that AML was a cutinase with a relatively exposed active site and specificity for medium chain fatty acyl moieties. AML rapidly hydrolysed the aliphatic plastics poly(ε-caprolactone) and poly(1,4-butylene succinate) extended with 1,6-diisocyanatohexane under mild conditions. These plastics are known to be slow to degrade in landfill. Poly(L-lactic acid) was not hydrolysed by AML, nor was the aromatic plastic Polyethylene Terephthalate (PET). The specificity of AML is partly explained by active site topology and analysis reveals that minor changes in the active site region can have large effects on substrate preference. These findings show that extracellular Amycolatopsis enzymes are capable of degrading a wider range of plastics than is generally recognised. The potential for application of AML in the bioremediation of plastics is discussed.Regulatory T cells (Tregs) are enriched in the tumor microenvironment and play key roles in immune evasion of cancer cells. Cell surface markers specific for tumor-infiltrating Tregs (TI-Tregs) can be effectively targeted to enhance antitumor immunity and used for stratification of immunotherapy outcomes. Here, we present a systems biology approach to identify functional cell surface markers for TI-Tregs. We selected differentially expressed genes for surface proteins of TI-Tregs and compared these with other CD4+ T cells using bulk RNA-sequencing data from murine lung cancer models. Thereafter, we filtered for human orthologues with conserved expression in TI-Tregs using single-cell transcriptome data from patients with non-small cell lung cancer (NSCLC). To evaluate the functional importance of expression-based markers of TI-Tregs, we utilized network-based measure of context-associated centrality in a Treg-specific coregulatory network. We identified TNFRSF9 (also known as 4-1BB or CD137), a previously reported target for enhancing antitumor immunity, among the final candidates for TI-Treg markers with high functional importance score. We found that the low TNFRSF9 expression level in Tregs was associated with enhanced overall survival rate and response to anti-PD-1 immunotherapy in patients with NSCLC, proposing that TNFRSF9 promotes immune suppressive activity of Tregs in tumor. Collectively, these results demonstrated that integrative transcriptome and network analysis can facilitate the discovery of functional markers of tumor-specific immune cells to develop novel therapeutic targets and biomarkers for boosting cancer immunotherapy.