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Vitamin K-dependent carboxylation is vital for human health. Here, authors present cryo-EM structures of the relevant γ-glutamyl carboxylase, uncovering substrate recognition, processive modification, and a bicarbonate-mediated CO₂ fixation mechanism.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

This study reveals the structural basis of collagen processing by the KOGG complex, revealing how it catalyzes lysine hydroxylation and dual-glycosylation, essential for collagen folding and stability, with implications for collagen-related diseases.

Lai et al. present a spatially resolved atlas of human atherosclerotic plaques, revealing cellular heterogeneity and identifying lymphoid structures and their potential functions and implications.

During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.

Collagen requires complicated modifications for proper assembly. Here, the authors show the structural basis of human collagen processing by the P3H1/CRTAP/PPIB complex, revealing a ‘face-to-face’ catalytic site configuration, collagen binding sites, and transition between trimer and hexamer states.

This study provides structural insights into human AE3’s role in pH regulation in excitable tissues, highlighting its structural differences from AE2 in anion transport regulation and their sensitivity to inhibitors.

Huang et al. report the tertiary structure of a small monomeric fluorogenic RNA aptamer named Clivia, characterized by a large Stokes shift, revealing the fluorescence activation mechanism and enabling a multivalent design to enhance the fluorescence output at specific dye concentrations.

piRNA processing factors and piRNA/PIWI complex are found in intermitochondrial cement (IMC) and chromatoid body (CB). Here, the authors show that piRNA loading orchestrates MIWI translocation from the IMC to CB, demonstrating its crucial role in spermatogenesis.

Lack of trabeculation compromises heart structure and function. How myocardial trabeculation is regulated by nonmyocytes is poorly understood. Researchers found that histone deacetylase 3 in the developing endocardial cells guides myocardial trabeculation by inducing growth signals.

Synthetic biology applications require finely tuned gene expression, often mediated by synthetic transcription factors. Here the authors validate two plant-derived proteins, FHY1 and FHL, acting as transactivators in mammalian cells for orthogonal, modular, and tunable control of gene transcription by forming a photosensing transcriptional regulation complex with PhyA.

Epigenetic changes can drive drug resistance in cancer. Here, the authors show that in BET inhibitor resistant leukaemia cells, genome-wide enhancer remodelling drives therapeutic resistance and targeting enhancer plasticity may overcome this resistance.

IFIs pose a significant threat to immunocompromised individuals, and there is an urgent need for rapid and sensitive diagnostic assays. Here, the authors present a rapid molecular diagnostic method based on magnetic fungal enrichment and CRISPR-based detection.

Cells maintain a narrow physiological pH by exchanging intracellular bicarbonate for extracellular chloride. Here, authors determine the cryo-EM structures of human anion exchanger 2 (AE2) in five major operating states and one transitional state, to collectively demonstrate the process of pH-balancing.

Qiao et al. report the design and characterization of an optogenetic platform for the dynamic control of protein expression and secretion by engineered bacteria, with implications for cancer therapy.

The crystal structure of the phage anti-CRISPR protein AcrF3 in complex with Cas3 reveals its mode of inhibition of the CRISPR–Cas bacterial immune system.

Highly sensitive photoswitchable dimerizer enables the control of biological processes with red light in mammals.

The development of broad-spectrum antivirals is an important part of pandemic preparedness and response. Here the authors present ALICE, synthetic biology designer immune-like cells that act as a sense-and-destroy antiviral system can detect viruses from seven different genera, mimicking the human innate immune system.

Very-long-chain fatty acids (VLCFAs) mediate recruitment of septins to the plasma membrane in fungal appressoria, leading to formation of a septin ring at the point of plant infection. VLCFA biosynthesis-inhibiting chemicals prevent septin assembly and have broad-spectrum fungicidal activity.

Multi-omics analysis reveals that differential plant performance among Populus species is associated with Pseudomonas in the rhizosphere. Further mechanistic investigation identifies GL3 as a regulator of flavone biosynthesis contributing to Pseudomonas recruitment.

Margaret Goodell, Wei Li and colleagues report conditional ablation of the Dnmt3a DNA methyltransferase in hematopoietic stem cells (HSCs) in mice. They show that Dnmt3a is critical for epigenetic silencing of HSC regulatory genes and for HSC differentiation.

While recurrence is frequent in ependymoma, the underlying molecular mechanisms remain to be explored. Here, the authors investigate epigenetic, genetic and tumorigenic changes in 30 patient-matched repeated relapses over 13 years and identify distinct patterns of DNA methylation.

Structural insights into the Derlin-1/p97 complex reveal a dynamic 6:6 architecture that expands the ERAD retrotranslocation pathway, highlighting ATPase-powered plasticity in processing bulky substrates.

The increase in detoxification gene expression is a common transcriptome marker for longevity interventions. Here, the authors show that nomilin extends lifespan and healthspan in animals through activation of PXR regulated detoxification functions.

Wolbachia induced cytoplasmic incompatibility (CI) is caused by linked pairs of genes named cifA and cifB. Here, authors show that the residues at interfaces of the CidA-CidB complex is crucial for their binding and contribute to the diversity of CI.

Alveoli are the lung’s functional units composed of two major epithelial cell types, type I and type II. Type II cells are adult lung stem cells, but this study shows that differentiated Type I cells can also self-renew and give rise to Type II cells, revealing a bidirectional relationship between lung epithelial cell types.

Researchers unveiled the structural details of sphingomyelin synthase (SMSr), shedding light on its role in sphingolipid biosynthesis. SMSr transfers the phosphoethanolamine from PE to ceramide, adding complexity to the field of lipid homeostasis.

Margaret Goodell and colleagues report genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified mouse hematopoietic stem cells. They identify large regions of low methylation with borders marked by 5-hydroxymethylcytosine. These borders become eroded in the absence of DNA methyltransferase 3a.

IFT-A plays crucial roles in bidirectional ciliary transport, vital for cilia biogenesis and signaling. Here, Ma et al. report the IFT-A structure in two distinct states and unveil the assembly mechanism of IFT-A into the anterograde train.

A diverse intestinal microbiota is required for mice to undergo extinction-related neuronal plasticity and normal fear extinction learning.

SPX proteins sense phosphate levels in plant cells by binding to inositol polyphosphates (InsP) and suppressing the activity of PHR transcription factors. Here the authors show that when bound to InsP₆, the rice SPX1 protein inhibits the activity of PHR2 by attenuating both its dimerization and DNA binding activity.

Zhang et al. report that the lncRNA H19 stabilizes dystrophin by competing with the ubiquitin E3 ligase TRIM63 for association with dystrophin, thereby alleviating muscular dystrophies.

Tet-mediated DNA demethylation is intimately involved in reguatling embryonic development. Here the authors characterise DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice and provide evidence that Tet-mediated DNA demethylation plays a role in regulating chromatin organization during early heart development.

It has been suggested that the magnetic properties of metal layers using reversible redox reactions could form the basis of memory devices but this requires fast electric control to be practical. Here the authors demonstrate this on sub-millisecond timescales in a metal–oxide heterostructure.

Pachytene piRNAs are abundant piRNAs in mammalian adult testes but their biogenesis pathway is not fully understood. Here, the authors identify TDRD5 as a piRNA biogenesis factor in mice, showing that it binds piRNA precursors and promotes pachytene piRNA production from specific transcript regions.