More than 10,000-fold enhanced magnetic resonance signals with >20-min signal lifetimes on universal biomolecular markers.

A systematic interrogation of male germ cells is key to complete understanding of molecular mechanisms governing spermatogenesis and the development of new strategies for infertility therapies and male contraception. Here we develop an approach to purify all types of homogeneous spermatogenic cells by combining transgenic labeling and synchronization of the cycle of the seminiferous epithelium, and subsequent single-cell RNA-sequencing. We reveal extensive and previously uncharacterized dynamic processes and molecular signatures in gene expression, as well as specific patterns of alternative splicing, and novel regulators for specific stages of male germ cell development. Our transcriptomics analyses led us to discover discriminative markers for isolating round spermatids at specific stages, and different embryo developmental potentials between early and late stage spermatids, providing evidence that maturation of round spermatids impacts on embryo development. This work provides valuable insights into mammalian spermatogenesis, and a comprehensive resource for future studies towards the complete elucidation of gametogenesis.

Epithelial-to-mesenchymal transition (EMT) promotes both tumor progression and drug resistance, yet few vulnerabilities of this state have been identifi ed. Using selective small molecules as cellular probes, we show that induction of EMT greatly sensitizes cells to agents that perturb endoplasmic reticulum (ER) function. This sensitivity to ER perturbations is caused by the synthesis and secretion of large quantities of extracellular matrix (ECM) proteins by EMT cells. Consistent with their increased secretory output, EMT cells display a branched ER morphology and constitutively activate the PERK-eIF2α axis of the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK) activation is also required for EMT cells to invade and metastasize. In human tumor tissues, EMT gene expression correlates strongly with both ECM and PERK-eIF2α genes, but not with other branches of the UPR. Taken together, our fi ndings identify a novel vulnerability of EMT cells, and demonstrate that the PERK branch of the UPR is required for their malignancy. SIGNIFICANCE:EMT drives tumor metastasis and drug resistance, highlighting the need for therapies that target this malignant subpopulation. Our fi ndings identify a previously unrecognized vulnerability of cancer cells that have undergone an EMT: sensitivity to ER stress. We also fi nd that PERK-eIF2α signaling, which is required to maintain ER homeostasis, is also indispensable for EMT cells to invade and metastasize. Cancer Discov; 4(6);

Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) and nitrogen-15 targets in particular. We show that 15N-SABRE works more efficiently and on a wider range of substrates than 1H-SABRE, greatly generalizing the SABRE approach. In addition, we show that nitrogen-15 offers significantly extended T1 times of up to 12 minutes. Long T1 times enable higher hyperpolarization levels but also hold the promise of hyperpolarized molecular imaging for several tens of minutes. Detailed characterization and optimization are presented, leading to nitrogen-15 polarization levels in excess of 10% on several compounds.

The concept of coding metasurface makes a link between physically metamaterial particles and digital codes, and hence it is possible to perform digital signal processing on the coding metasurface to realize unusual physical phenomena. Here, this study presents to perform Fourier operations on coding metasurfaces and proposes a principle called as scattering‐pattern shift using the convolution theorem, which allows steering of the scattering pattern to an arbitrarily predesigned direction. Owing to the constant reflection amplitude of coding particles, the required coding pattern can be simply achieved by the modulus of two coding matrices. This study demonstrates that the scattering patterns that are directly calculated from the coding pattern using the Fourier transform have excellent agreements to the numerical simulations based on realistic coding structures, providing an efficient method in optimizing coding patterns to achieve predesigned scattering beams. The most important advantage of this approach over the previous schemes in producing anomalous single‐beam scattering is its flexible and continuous controls to arbitrary directions. This work opens a new route to study metamaterial from a fully digital perspective, predicting the possibility of combining conventional theorems in digital signal processing with the coding metasurface to realize more powerful manipulations of electromagnetic waves.