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By analyzing the structures of the Polycomb repressive deubiquitinase complex, which catalyzes the deubiquitination of H2AK119Ub on nucleosomes, Zhang, Zheng, Tong and Deng et al. reveal that ubiquitin acts as a proteinaceous glue to fasten the intersubunit interaction within the complex to allosterically enhance its activity.

Tong et al. chemically trapped the structure of the E4 enzyme Ufd2, which mediates K48 branched ubiquitination on K29diUb and K29triUb, identifying Ufd2’s core region as a K29diUb binding domain and a dimeric conformation for distal ubiquitin stabilization.

ALKBH8 is a tRNA methyltransferase, specifically modifying the wobble uridine (U34) in tRNAs. Here, the authors discover that ALKBH8 is a direct transcriptional target of β-catenin, and that mediates intestinal tumorigenesis through regulation of the translation of KRAS in a codon-dependent manner.

Ubiquitin E3 ligases are key to accessing ubiquitinated proteins, but only a few substrates have defined E3 ligases. Here, the authors reveal the mechanism of naturally occurring E3-independent ubiquitination and develop an E3-free enzymatic strategy for the versatile generation of ubiquitinated proteins.

The K29/K48 hetero-polyubiquitin signal has been reported to be an enhanced degradation signal, but the enzymatic mechanism of this ubiquitin chain formation is unclear. Here, the authors reveal how the HECT E3 ligase Ufd4/TRIP12 generates K29/K48 branched ubiquitin chains and provide structural insights into this process.

Dual targeting of BRAF and MAPK signaling in the BRAF v600E mutant colorectal cancer patients has shown limited efficacy in clinical studies. Here, the authors identify PLK1 inhibition as synthetic lethal with dual BRAF and EGFR inhibition due to loss of ferroptosis inhibition via a PLK1-CBX8-GPX4 signaling axis in preclinical models of colorectal cancer.

By engineering boundary conditions, the authors obtain the self-assembly two-order ferroelectric radial vortices in high-density BiFeO3 nanostructures. Tuning the size of the BiFeO3 nanostructures enables stabilization of other kinds of multi-order radial vortices.

Dissection of the physiological interactomes of histone post-translational modifications is crucial for understanding epigenetic regulatory pathways. Here, authors develop a nucleus-targeting histone-tail-based photoaffinity probe capable of profiling the hPTM-mediated interactomes in native cells.

Topological structures could spark promising functionalities in next generation nanoelectronics. Here, the authors report the realization of complex topological polar textures in epitaxial multiferroic BiFeO₃ –SrTiO₃ superlattices induced by competing electrical and mechanical boundary conditions.

Using site-specific chemical crosslinking strategies, Ai, Tong and Deng et al. captured structural intermediates of ubiquitin E3 ligase RNF168-mediated H2A K13 and K15 monoubiquitination and adjacent dual monoubiquitination in the DNA damage repair response; the structural analysis revealed a helix-anchoring mechanism.

Bone is a dynamic tissue and requires the precise coordination of formation with loss. Here, Xu Cao and his colleagues show that the bone-chewing activity of osteoclasts results in the local release of active TGF-β1 from the surface of the bone, inducing the migration of nearby bone-forming osteoblastic progenitor cells to this resorbed region. In this manner, proper matching of the localized rates of bone loss and bone creation is ensured (pages 729–731).

Activation of white adipose tissue (WAT) thermogenesis alleviates obesity-associated metabolic disorders in rodents. Here the authors report that the m6 A RNA modification reader YTHDF1 promotes WAT thermogenesis in a study with male mice, and may be a potential target for the treatment of obesity.

The 1T′ phase of MoS₂ monolayers, as well as the 2H phase and their heterophase bilayers, can be grown directly by tuning the potassium concentration in the reaction atmosphere. The pure 1T′ phase demonstrates in-plane anisotropic properties.

Fast intermetallic electron transfer is expected in principle in nanozised transition metal complexes, but has been prevented by the bridging ligands. Here the authors synthesize a mixed-valence iron metal-ligand nanocluster with cyanide bridges, showing extended delocalized electronic structure

Cancer chemoprevention approaches generally use long-term, continuous treatment, which can lead to adverse events. This Opinion article discusses whether short-term, intermittent therapy that exploits synthetic lethal interactions in premalignant cells might reduce the toxicity of chemoprevention while retaining its benefits.

Two-dimensional transition metal dichalcogenides with peculiar spin–orbit coupling may lead to exotic phenomena. Here, the authors report a large in-plane upper critical field with a two-fold symmetry, suggesting a novel asymmetric spin–orbit coupling in few-layer 1T_d-MoTe₂.

Remodeling complexes can affect DNA transactions by altering chromatin, thus affecting accessibility of DNA. The INO80 remodeling complex has previously been implicated in replication and analyses now argue that it specifically acts through the DNA damage tolerance pathways that resolve recombination intermediates at impeded replication forks.

In response to parathyroid hormone (PTH), TGF-β type II receptor (TβRII) directly phosphorylates the PTH type I receptor (PTH1R) and modulates PTH-induced endocytosis of a PTH1R/TβRII complex. Mice that lack TβRII display higher bone mass — a phenotype similar to that observed in mice expressing a constitutively active version of PTH1R.

Bone remodeling involves a coupled balance between bone resorption and bone formation. Xu Cao and his colleagues have shown before that mesenchymal stem cells (MSCs) are recruited to the surface of the bone during this process. They now show that insulin-like growth factor 1 (IGF-1) is released from the bone surface during bone resorption, where it signals the recruited MSCs to differentiate into osteoblasts. In this way, bone resorption is linked to bone formation, and IGF-1 as a target of bone therapy is suggested.

Molten-salt-assisted chemical vapour deposition is used to synthesize a wide variety of two-dimensional transition-metal chalcogenides.

Cancer 'chemoprevention' uses substances to reverse, suppress or prevent the initial phase of carcinogenesis or the progression of neoplastic cells to cancer cells. Here it is shown that treatment with TRAIL proteins and all-trans-retinyl acetate can cause the death, in vitro and in vivo, of premalignant cells deficient in the adenomatous polyposis coli gene. Normal cells are unaffected. Selectively eliminating premalignant tumour cells in this way is thus an effective method for chemoprevention.

Multidrug and radiation resistance, as well as nonspecific toxic effects of some drugs, currently limit some cancer therapies. Ekaterina Lukianova-Hleb and colleagues address this with the development of an intracellular drug release system using plasmonic nanobubbles for the on-demand release of the encapsulated payload from nanocarriers, achieving high target cell specificity and intracellular concentration and enhanced therapeutic efficacy of both drugs and X-rays. Validation is shown in aggressive and multidrug resistant head and neck squamous cell carcinoma using encapsulated doxorubicin and paclitaxel.

In this study, the authors show that metformin, a drug primarily used for the treatment of diabetes, provides protection against cryoinjuries in porcine oocytes by reducing membrane fluidity and mitochondrial activity.

Perovskite nanocrystals are promising for use in light emitting diodes, but improved hole injection is needed. Here, MoO₃ is added as an electric dipole layer between hole injection and transport layers, achieving a current efficiency of 72.7cd/A in a green light emitting diode.