) system. Here we report the design of multicolor versions of CRISPR using catalytically inactive Cas9 endonuclease (dCas9) from three bacterial orthologs. Each pair of dCas9-fluorescent proteins and cognate single-guide RNAs (sgRNAs) efficiently labeled several target loci in live human cells. Using pairs of differently colored dCas9-sgRNAs, it was possible to determine the intranuclear distance between loci on different chromosomes. In addition, the fluorescence spatial resolution between two loci on the same chromosome could be determined and related to the linear distance between them on the chromosome's physical map, thereby permitting assessment of the DNA compaction of such regions in a live cell.1f:T518,Understanding the reaction mechanism for the catalytic process is essential to the rational design and synthesis of highly efficient catalysts. MoS₂ has been reported to be an efficient catalyst toward the electrochemical hydrogen evolution reaction (HER), but it still lacks direct experimental evidence to reveal the mechanism for MoS₂-catalyzed electrochemical HER process at the atomic level. In this work, we develop a wet-chemical synthetic method to prepare the single-layer MoS₂-coated polyhedral Ag core-shell heterostructure (Ag@MoS₂) with tunable sizes as efficient catalysts for the electrochemical HER. The Ag@MoS₂ core-shell heterostructures are used as ideal platforms for the real-time surface-enhanced Raman spectroscopy (SERS) study owing to the strong electromagnetic field generated in the plasmonic Ag core. The in situ SERS results provide solid Raman spectroscopic evidence proving the S-H bonding formation on the MoS₂ surface during the HER process, suggesting that the S atom of MoS₂ is the catalytic active site for the electrochemical HER. It paves the way on the design and synthesis of heterostructures for exploring their catalytic mechanism at atomic level based on the in situ SERS measurement.

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