The jumonji (JMJ) family of histone demethylases are Fe2+- and α-ketoglutarate-dependent oxygenases that are essential components of regulatory transcriptional chromatin complexes1–4. These enzymes demethylate lysine residues in histones in a methylation-state and sequence-specific context5. Considerable effort has been devoted to gaining a mechanistic understanding of the roles of histone lysine demethylases in eukaryotic transcription, genome integrity and epigenetic inheritance2,4,6, as well as in development, physiology and disease3,7. However, because of the absence of any selective inhibitors, the relevance of the demethylase activity of JMJ enzymes in regulating cellular responses remains poorly understood. Here we present a structure-guided small-molecule and chemoproteomics approach to elucidating the functional role of the H3K27me3-specific demethylase subfamily (KDM6 subfamily members JMJD3 and UTX)8. The liganded structures of human and mouse JMJD3 provide novel insight into the specificity determinants for cofactor, substrate and inhibitor recognition by the KDM6 subfamily of demethylases. We exploited these structural features to generate the first small-molecule catalytic site inhibitor that is selective for the H3K27me3-specific JMJ subfamily. We demonstrate that this inhibitor binds in a novel manner and reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX. Our results resolve the ambiguity associated with the catalytic function of H3K27-specific JMJs in regulating disease-relevant inflammatory responses and provide encouragement for designing small-molecule inhibitors to allow selective pharmacological intervention across the JMJ family.

MXene films are attractive for advanced supercapacitor electrodes requiring high volumetric energy density due to their high redox capacitance combined with extremely high packing density. However, the self‐restacking of MXene flakes unavoidably decreases the volumetric performance, mass loading, and rate capability. Herein, a simple strategy is developed to prepare a flexible and free‐standing modified MXene/holey graphene film by filtration of the alkalized MXene and holey graphene oxide dispersions, followed by a mild annealing treatment. After terminal groups (—F/—OH) are removed, the increased proportion of Ti atoms enables more pseudocapacitive reaction. Meanwhile, the embedded holey graphene effectively prevents the self‐restacking of MXene and forms a high nanopore connectivity network, which is able to immensely accelerate the ion transport and shorten transport pathways for both ion and electron. When applied as electrode materials for supercapacitors, it can deliver an ultrahigh volumetric capacitance (1445 F cm−3) at 2 mV s−1, excellent rate capability, and high mass loading. In addition, the assembled symmetric supercapacitor demonstrates a fantastic volumetric energy density (38.6 Wh L−1), which is the highest value reported for MXene‐based electrodes in aqueous electrolytes. This work opens a new avenue for the further exploration of MXene materials in energy storage devices.

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Recently, superhydrophobic surfaces with tunable wettability have aroused much attention. Noticeably, almost all present smart performances rely on the variation of surface chemistry on static micro/nanostructure, to obtain a surface with dynamically tunable micro/nanostructure, especially that can memorize and keep different micro/nanostructures and related wettabilities, is still a challenge. Herein, by creating micro/nanostructured arrays on shape memory polymer, a superhydrophobic surface that has shape memory ability in changing and recovering its hierarchical structures and related wettabilities was reported. Meanwhile, the surface was successfully used in the rewritable functional chip for droplet storage by designing microstructure-dependent patterns, which breaks through current research that structure patterns cannot be reprogrammed. This article advances a superhydrophobic surface with shape memory hierarchical structure and the application in rewritable functional chip, which could start some fresh ideas for the development of smart superhydrophobic surface.

The NSD family histone methyltransferases, including NSD1, NSD2 and NSD3, play crucial roles in chromatin regulation and are implicated in oncogenesis 1 , 2 . NSD enzymes exhibit an auto-inhibitory state that is relieved by nucleosome engagement, allowing for H3K36 di-methylation catalysis 3 – 7 . However, the molecular basis underlying this mechanism is largely unknown. Here, we have solved the cryo-EM structures of NSD2 and NSD3 bound to mononucleosomes at atomic resolution. We find that NSD2/3 mononucleosome engagement causes DNA near the linker region to unwrap, which facilitates insertion of their catalytic core in-between the histone octamer and the unwrapped segment of DNA. A network of DNA- and histone-specific contacts between the nucleosome and NSD2/3 precisely define the enzymes’ position on the nucleosome, explaining the methylation specificity for H3K36. Further, NSD-nucleosome intermolecular contacts are altered by several recurrent cancer-associated NSD2/3 mutations. NSDs harboring these mutations are catalytically hyperactive in vitro and in cells, and their ectopic expression promotes cancer cell proliferation and xenograft tumor growth. Together, our research provides molecular insights into the nucleosome-based recognition and modification mechanisms of NSD2 and NSD3, which should uncover strategies for therapeutic targeting of the NSD family of proteins.

Recently, materials with controlled oil/water separation ability became a new research focus. Herein, we report a novel copper mesh film, which is superhydrophobic and superhydrophilic for nonalkaline water and alkaline water, respectively. Meanwhile, the film shows superoleophobicity in alkaline water. Using the film as a separating membrane, the oil/water separating process can be triggered on-demand by changing the water pH, which shows a good controllability. Moreover, it is found that the nanostructure and the appropriate pore size of the substrate are important for realization of a good separation effect. This paper offers a new insight into the application of surfaces with switchable wettability, and the film reported here has such a special ability that allows it to be used in other applications, such as sewage purification, filtration, and microfluidic device.

MXene films are attractive for use in advanced supercapacitor electrodes on account of their ultrahigh density and pseudocapacitive charge storage mechanism in sulfuric acid. However, the self-restacking of MXene nanosheets severely affects their rate capability and mass loading. Herein, a free-standing and flexible modified nanoporous MXene film is fabricated by incorporating Fe(OH)3 nanoparticles with diameters of 3-5 nm into MXene films and then dissolving the Fe(OH)3 nanoparticles, followed by low calcination at 200 °C, resulting in highly interconnected nanopore channels that promote efficient ion transport without compromising ultrahigh density. As a result, the modified nanoporous MXene film presents an attractive volumetric capacitance (1142 F cm-3 at 0.5 A g-1) and good rate capability (828 F cm-3 at 20 A g-1). Furthermore, it still displays a high volumetric capacitance of 749 F cm-3 and good flexibility even at a high mass loading of 11.2 mg cm-2. Therefore, this flexible and free-standing nanoporous MXene film is a promising electrode material for flexible, portable and compact storage devices. This study provides an efficient material design for flexible energy storage devices possessing high volumetric capacitance and good rate capability even at a high mass loading.

A facile strategy for the preparation of multifunctional Janus membranes was proposed, and excellent controllability of the membrane was demonstrated.