to mass spectrometry related experiments and analysis; R.H., Z.Y. and B.R. performed the library construction and next-generation sequencing for ChIP-seq and RNA-seq; M.H. and Y.G.Z. synthesized L-lactyl-CoA. H.H. and D.Z. analyzed ChIP-seq and RNA-seq data. G.Z. provided all primary BMDM cell cultures. D.M.C. carried out the bacterial infection experiments, C.C. carried out TAM experiments. Author Information. Y.Z. is a founder, board member, advisor to, and inventor on patents licensed to PTM Bio Inc. L.B. is co-founder and CSO of rMark Bio Inc., and founder and CEO of Onchilles Pharma Inc. Readers are welcome to comment on the online version of the paper. Data availability. The ChIP-seq and RNA-seq data have been made available at the Gene Expression Omnibus (GEO) repository under the accession number GSE115354. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE 31 partner repository with the dataset identifier PXD014870. All other data are available from the authors upon reasonable request.

Optical imaging of diseases represents a highly dynamic and multidisciplinary research area, and second near-infrared window (NIR-II, 1000–1700 nm) imaging is at the forefront of the research on optical imaging techniques.

The amaryllidaceae family consists of about 75 genera and 1100 species that are wide-spread in the tropics and warm temperate regions of the world. Since the first isolation of lycorine, more than 500 amaryllidaceae alkaloids have been isolated over the past three decades. The enormous numbers of diverse amaryllidaceae alkaloids are classified into different groups mainly according to their structural features. The representative alkaloids are norbelladine, lycorine, hippeastrine, narwedine, haemanthamine, pancratistatin, pretazettine, montanine, galanthindole, cherylline and ismine. Recently, more extensive studies have revealed that amaryllidaceae alkaloids exhibit a wide range of bioactivities, such as antitumor, antiviral, antibacterial, antifungal, antimalarial and analgesic. Acetylcholinesterase (AChE) inhibitory and cytotoxic activities have also been reported. The aim of the present review is to discuss the recent developments on the biological and pharmacological activities of amaryllidaceae alkaloids with IC 50 or EC 50 values since 2005, supporting the potential therapeutic possibilities for the use of these compounds.

The side-chain acetylation of lysine residues in histones and non-histone proteins catalyzed by lysine acetyltransferases (KATs) represents a widespread posttranslational modification (PTM) in the eukaryotic cells. Lysine acetylation plays regulatory roles in major cellular pathways inside and outside the nucleus. In particular, KAT-mediated histone acetylation has an effect on all DNA-templated epigenetic processes. Aberrant expression and activation of KATs are commonly observed in human diseases, especially cancer. In recent years, the study of KAT functions in biology and disease has greatly benefited from chemical biology tools and strategies. In this Review, we present the past and current accomplishments in the design of chemical biology approaches for the interrogation of KAT activity and function. These methods and probes are classified according to their mechanisms of action and respective applications, with both strengths and limitations discussed.

Chemical modifications on the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The “histone code” hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) on the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and over 450 histone PTMs discovered, and the PTMs on lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood. In this study, we investigated how naturally occurring N-terminal acetylation and PTMs on histone H4 lysine-5 (H4K5) affect arginine-3 methylation catalyzed by both type I and type II PRMTs at the biochemical level. Our studies found that acylations of H4K5 resulted in decreased arginine methylation by PRMT1, PRMT3, and PRMT8. In contrast, PRMT5 exhibits increased arginine methylation upon H4K5 acetylation, propionylation, and crotonylation, but not upon H4K5 methylation, butyrylation, or 2-hydroxyisobutyrylation. Methylation of H4K5 did not affect arginine methylation by PRMT1 or PRMT5. There was a small increase in arginine methylation by PRMT8. Strikingly, a marked increase in arginine methylation was observed for PRMT3. Finally, N-terminal acetylation reduced arginine methylation by PRMT3, but had little influence on PRMT1, 5, and 8 activity. These results together highlight the underlying mechanistic differences in substrate recognition among different PRMTs and pay the way for the elucidation of the complex interplays of histone modifications.