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Chen et al. identify a brain-to-bone communication axis whereby extracellular vesicles from aged brain neurons transport WDFY1 protein to distal bone, driving bone-fat imbalance and promoting osteoporosis.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

Manipulating the chemical composition of proteins and peptides has been central to the development of polypeptide-based therapeutics and to help address fundamental biological questions. This Review describes how nature-inspired protein ligation strategies have been repurposed as chemical biology tools.

IsoNet, an isotopologue similarity networking strategy based on mass spectrometry-resolved stable-isotope tracing metabolomics, enables ab initio elucidation of unknown metabolites and their reactions, which is applied to the glutathione metabolic reaction network.

Huang and colleagues report that TIM4–AMPK signaling induces downregulation of the mitochondrial HSP90 chaperone TRAP1 in tumor-associated macrophages, thereby enhancing their immunoinhibitory function and promoting immune evasion and tumorigenesis.

The mechanism of how different anion dopants influence the catalytic performance for sulfur species is currently lacking systematic theoretical studies. Here, an accurate p-p-s electronic coupling descriptor was proposed as a criterion to guide the design of anion-doped Li-S catalysts.

In this work, the authors build on the high-resolution structural characterization of the tubulin-binding site and show that the microtubule inhibitor KY216 blocks NSCLC metastasis by prompting α-tubulin detyrosination and inhibiting the miR429/VASH2/ZEB1 axis.

In Caenorhabditis elegans, nociception and avoidance behaviour are crucial for survival, but their modulation is poorly understood. Here, the authors describe a cross-inhibitory neural circuit between ASH and ASI sensory neurons that fine-tunes nociception and mediates adaptive avoidance behaviour.

Li et al. characterized the gene GRAVITROPISM LOSS 1 (OsGLS1) in rice, which regulates root system architecture (RSA) to enhance nutrient uptake and yield. OsGLS1 promotes the degradation of OsPIN2, influencing auxin transport and root growth patterns.

Chaperone-mediated autophagy (CMA) is often dysregulated in cancer, but its mechanisms remain unclear. This study reveals that MST4- mediated LAMP2A phosphorylation regulates CMA by stabilizing lysosomal LAMP2A, thereby promoting GBM tumorigenicity and immune evasion.

The precise spatiotemporal control of chemokine exposure would be an advantageous tool for immune cell research. Here, Chen et al. develop a two-photon-activatable chemokine CCL5 and use it to direct lymphocyte migration in vivo and to show that PI3-kinase is not required to sense a gradient in vitro.

Translation inhibition is a strategy for organisms to overcome various environmental stresses including viral infections. Here the authors show that a tRNA/rRNA-targeting RNase Schlafen13 inhibits protein synthesis by directly digesting cytoplasmic tRNA and rRNA with the ability to restrict viral propagation.

Lu and colleagues delineate a pathway through which the PKM2 enzyme promotes aerobic glycolysis, known as the Warburg effect, in cancer cells. They show that EGFR-activated ERK phosphorylates PKM2, leading to its accumulation in the nucleus. Nuclear PKM2 subsequently promotes the c-Myc-dependent upregulation of genes involved in the Warburg effect, resulting in tumour growth.

The Shc1 scaffold mediates a switch in the signaling output of the epidermal growth factor receptor tyrosine kinase over time through recruitment of successive waves of proteins with distinct biological functions.

Ghrelin receptor regulates energy homeostasis through constitutive activity or by the ghrelin. Here the authors report two structures of ghrelin receptor bound to agonist and inverse agonist, providing insights into the mechanism of inverse agonism, which is of interest for specific ligand design.

Under conditions of energy starvation, the p38β–PRAK pathway is activated and inhibits mTORC1 by phosphorylating the small GTPase Rheb. This finding links a major stress response pathway with energy homeostasis.

This study reports that the CK2 kinase–H3K27 methyltransferase (PRC2) signalling promotes genome-wide H3K27 trimethylation and the formation of epigenetic cold memory at a potent floral repressor in Arabidopsis in response to prolonged cold exposure.

Chen et al. report on a renal UTX-phosphoglycerate dehydrogenase axis that regulates serine secretion to affect lipid metabolism in the kidney and liver upon over-nutrition, suggesting potential treatment targets for obesity-related diseases.

The kinase Plk1 regulates multiple processes during mitosis in mammalian cells. Chen and colleagues show that Plk1 also controls a transcriptional network required for orderly cell-cycle progression through Cdk1-dependent phosphorylation of the transcription factor FoxM1

Macrophage infection by Yersinia or specific stimulations trigger caspase-8-mediated GSDMD cleavage. RIOK2 kinase is essential for this process by interacting with FADD and driving the lysosome-to-ER transport of the cell death complex accompanied by GSDMD cleavage, thereby enhancing host defense.

GSK3 promotes trehalose biosynthesis by phosphorylating TPS at Ser-529, thereby regulating the mycelial growth and response to high temperatures.

This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.

TAAR1 has a rigid consensus binding motif that binds to endogenous trace amine stimuli as well as two extended binding pockets that accommodate diverse chemotypes.

Here, by characterizing 477 genomes from cultivated bacteria and metagenome-assembled genomes of the bee gut microbiota, the authors uncover uncharacterized biosynthetic gene clusters encoding small molecules with potential antimicrobial activity against bee pathogens, shedding light on the role of microbiome in honeybee health.

Native chemical ligation is pivotal in chemical protein synthesis but often requires excessive additives due to the low reactivity of peptide alkyl thioesters. Here, the authors introduce a thioacid-based additive-free peptide ligation using vinyl thianthrenium tetrafluoroborate, enhancing efficiency and simplicity in synthesizing complex proteins like hyalomin-3 and ubiquitin.

RinRK1 interacts with NFR1 and NFR5 through their extracellular domains, facilitating a complex with Flot1. This interaction promotes their localization at root hair tip nanodomains, crucial for mediating the rhizobial infection.

Immune check point therapies have not been successful for prostate cancers, but the underlying mechanisms are unclear. Here the authors show that a transcription factor, YY1, may promote the SUMOylation and stability of HIF-1α to suppress anti-tumor immunity, while targeting YY1 helps improve tumor control, in mouse prostate cancer models.

Tandem electro-biocatalytic systems present a versatile platform for producing a variety of synthetic products using CO₂ as a starting material. Here direct ocean carbon capture is incorporated into an electrolysis scheme to produce formic acid from CO₂ dissolved in seawater that is subsequently converted to succinate in a bioreactor.

Phylogenetic and biochemical analyses show a diversity of components of the DNA replication machinery in different Asgard archaea that contributed to the eukaryotic DNA replication machinery.

SLC26A2 transports crucial ions and mutations in it cause diverse diseases. Here, authors present cryo-EM structures of SLC26A2 with substrates, revealing details of its homodimer assembly, dynamic substrate binding, and effects of mutations.

Limited high quality multi-omics resources are available for plants with complex genomes. Here, authors generate transcriptome, proteome, phosphoproteome, and acetylproteome data sets across wheat developmental stages and reveal de-acetylation of TaP5CS1 by TaHDA9 regulates Fusarium crown rot resistance.

Methods for selective modification of the N-terminus of proteins are of high interest, but mostly require specific amino acid residues. Here, the authors report a selective and fast method for N-terminal modification of proteins based on quinone-mediated oxidation of the alpha-amine to aldehyde or ketone, and apply it to diverse proteins.

Chen et al. show that the endoplasmic reticulum stress sensor IRE1α acts in white and beige adipocytes to restrain beige adipocyte activation, through regulation of lipolysis and Pgc1α messenger RNA levels, respectively.

This study demonstrates a WAKL4 receptor-like kinase that is rapidly and specifically induced by Cadmium. It reveals a unique mechanism conferred by the WAKL4-NRAMP1 module that enables plants to actively respond to Cadmium and limit its uptake.

Rice blast disease caused by Magnaporth oryzae is one of the most devastating diseases to threaten sustainable rice production. This study reveals that OsUBC45, encoding a ubiquitin-conjugating enzyme, may be useful in improving disease resistance. Overexpression of OsUBC45 enhances resistance to both the blast disease and bacterial leaf blight, while also resulting in a significant increase in grain yield of over 10%.

The molecular mechanisms underlying metabolic remodelling in colorectal cancer (CRC) are not completely elucidated. Here, they authors show that the oncogenic protein MYG1 promotes CRC progression not only through regulating mitochondrial activity, but also through activating a nuclear-associated pathway for glycolysis increase.

How D-type cyclins become dysregulated in cancer remains to be understood. Here, the authors identify that F-box protein FBXO32 catalyzes the K27-linked polyubiquitination and subsequent stabilization of D-type cyclins, contributing to cancer progression in both liver and pancreatic tumor models.

The enzyme butyrylcholinesterase (BChE) can metabolize cocaine, albeit at relatively low speeds. Here the authors use computational methods to define mutations that increase BChE-mediated cocaine hydrolysis, achieving a catalytic activity comparable to that of one of the fastest naturally occurring enzyme.