The interaction between ionizing radiation and materials composed of high Z-number elements could be applied to enhance radiotherapy. In this work, we fabricated an ionizing radiation-sensitive nanoplatform by grafting chlorin e6 (Ce6) onto the surface of ultrasmall gold nanoparticles (Au NPs), aiming to enhance the radiation effects induced by different radiation sources. Poly(ethylene glycol) (PEG) was applied as the shape-controlling agent during the synthesis of Au nanoparticles. The as-prepared Au NPs show excellent monodispersity, with an average hydrodynamic diameter of around 5 nm. U87 and HeLa cell lines were utilized to evaluate the biological properties of the as-prepared Ce6–Au NPs. The Cell Counting Kit-8 (CCK-8) results reveal that the Ce6–Au NPs conjugate can significantly affect the growth of U87 cells under X-ray and 68Ga exposure, which is not seen for the pure Au NPs, Ce6, and physically mixed Ce6 and Au NPs. Moreover, the Ce6–Au NPs conjugate show evident cell prefoliation inhibition of U87 and HeLa cells under both X-ray and 18F-radiolabeled fluorodeoxyglucose (18F-FDG) exposure. These results indicate that interaction exists between Ce6 and Au NPs under radiation exposure. The mRNA sequencing results show that the tumor killing performance induced by Ce6–Au NPs may be due to regulation of the tumor microenvironment (TME) and immune-relevant signaling pathway. Our research proves that the rational combination of Au NPs and Ce6 can make better use of ionizing radiation energy and thus improve the therapeutic outcome of radiotherapy.

The development of clinical imaging techniques significantly improves diagnostic accuracy and provides guidance for personalized treatment of individuals. However, every single imaging modality has its distinct drawbacks that cannot fully fulfil the diagnosis requirement. Thus, rational combination of different imaging modalities can achieve more comprehensive information of disease and in this way provide better personalized treatment strategy. The hybrid PET/MRI has drawn increasing attention since its first clinical application. Imaging probes play an essential role in achieving qualified figures with accurate information of diseases. The application of nanotechnology promotes the development of versatile molecular probes for PET/MRI technique. Though there is an emerging clinical requirement, only a small number of multimodal PET/MRI probes have been investigated in preclinical research. Thus, this review tries to thoroughly summarize the nano-sized PET/MRI probes on their design, preparation and biological application. By discussing the strength and limitations of these current available PET/MRI multimodal probes, this work aims to figure out the further research direction and promote the possible clinic translation of the novel PET/MRI probes.

Saccharomyces pastorianus strains are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus that have been domesticated for centuries in lager beer brewing environments. As sequences and structures of S. pastorianus genomes are being resolved, molecular mechanisms and evolutionary origins of several industrially relevant phenotypes remain unknown. This study investigates how maltotriose metabolism, a key feature in brewing, may have arisen in early S. eubayanus α S. cerevisiae hybrids. To address this question, we generated a nearly complete genome assembly of Himalayan S. eubayanus strains of the Holarctic subclade. This group of strains has been proposed to be the S. eubayanus subgenome origin of current S. pastorianus strains. The Himalayan S. eubayanus genomes harbored several copies of an S. eubayanus AGT1 (SeAGT1) α-oligoglucoside transporter gene with high sequence identity to genes encountered in S. pastorianus. Although Himalayan S. eubayanus strains cannot grow on maltose and maltotriose, their maltose-hydrolase and SeMALT1 and SeAGT1 maltose transporter genes complemented the corresponding null mutants of S. cerevisiae. Expression, in Himalayan S. eubayanus of a functional S. cerevisiae maltose metabolism regulator gene (MALx3) enabled growth on oligoglucosides. The hypothesis that the maltotriose-positive phenotype in S. pastorianus is a result of heterosis was experimentally tested by constructing an S. cerevisiae α S. eubayanus laboratory hybrid with a complement of maltose metabolism genes that resembles that of current S. pastorianus strains. The ability of this hybrid to consume maltotriose in brewer's wort demonstrated regulatory cross talk between subgenomes and thereby validated this hypothesis. These results support experimentally the new postulated hypothesis on the evolutionary origin of an essential phenotype of lager brewing strains and valuable knowledge for industrial exploitation of laboratory-made S. pastorianus-like hybrids. IMPORTANCE S. pastorianus, an S. cerevisiae α S. eubayanus hybrid, is used for production of lager beer, the most produced alcoholic beverage worldwide. It emerged by spontaneous hybridization and colonized early lager brewing processes. Despite accumulation and analysis of genome sequencing data of S. pastorianus parental genomes, the genetic blueprint of industrially relevant phenotypes remains unresolved. Assimilation of maltotriose, an abundant sugar in wort, has been postulated to be inherited from the S. cerevisiae parent. Here, we demonstrate that although Asian S. eubayanus isolates harbor a functional maltotriose transporter SeAGT1 gene, they are unable to grow on α-oligoglucosides, but expression of S. cerevisiae regulator MAL13 (ScMAL13) was sufficient to restore growth on trisaccharides. We hypothesized that the S. pastorianus maltotriose phenotype results from regulatory interaction between S. cerevisiae maltose transcription activator and the promoter of SeAGT1. We experimentally confirmed the heterotic nature of the phenotype, and thus these results provide experimental evidence of the evolutionary origin of an essential phenotype of lager brewing strains.