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The authors report on engineering metazoan fatty acid synthase variants with tunable selectivity to obtain short- and medium-chain fatty acids, alcohols and aldehydes. Pairing these optimized enzymes with a yeast strain designed for efficient β-oxidation yields high production levels of medium-chain fatty acids.

A key step in the evolution of the nitrogen-fixing root nodule symbiosis, occurring 100 million years ago, subjected the control of Nodule Inception (NIN) gene expression to a protein complex that regulated transcription much earlier in the arbuscular mycorrhiza symbiosis.

Using brain organoids models, Prigione and colleagues uncovered the impact of Huntington’s disease on human brain developmental and identified early dysregulation of CHCHD2, which disrupted mitochondria and might serve as a therapeutic target.

Cancer patients are at increased risk for severe bacterial infections due to immune dysfunction. Here, the authors show that chronic tumor-derived G-CSF drives NAMPT/NAD-dependent neutrophil dysfunction from the progenitor stage, and that targeting this pathway restores infection control.

Histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division.

Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

Antibodies targeting the spike protein of coronaviruses are potential candidates for therapeutic development. Here, Bertoglio et al. use phage display to select anti-SARS-CoV-2 spike antibodies from the human naïve universal antibody gene libraries HAL9/10 that block interaction with ACE2 receptor to inhibit infection.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

MethyLYZR, an epigenetic classifier of brain tumors, provides clinically relevant cancer classification results within 15 min of sequencing, with potential applications for neurosurgical intraoperative use.

Gram-negative bacteria rely on the Ton system for nutrient uptake. Here, authors uncover how the ExbD protein acts as a conformational switch and the function of peptidoglycan in order to energize this transport process across the outer membrane.

MYC drives S-phase progression and immune invasion in pancreatic ductal adenocarcinoma (PDAC), but the underlying mechanisms are not fully understood. Here, the authors show that the transcription elongation complex PAF1c controls the competition of different gene sets for RNA polymerase and elongation factors to regulate these MYC-associated mechanisms in PDAC.

Merz and colleagues perform single-cell multiomic analysis of mononuclear cells isolated from individuals receiving BCMA-directed CAR T cell therapy for myeloma and show that nonresponders are characterized by an immune-suppressive microenvironment.

A method combining genetic-code expansion, bioorthogonal Staudinger reduction and sortase-mediated transpeptidation enables site-specific and orthogonal modification of proteins with ubiquitin and SUMO in vitro and in living cells.

Motility coupled with responsive behavior is essential for microorganisms to establish suitable habitats, with simple responses like reversing motion enabling them to form stable aggregates. Kurjahn et al. show that filamentous cyanobacteria use light gradients and boundary curvature of light stimuli to form ordered, entangled aggregates, revealing how these dynamics could influence adaptive colony architectures.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

SARS-CoV-2 mutations associated with the escape from antibody-mediated neutralization have been widely reported. Here, in a patient with defective antibody responses, the authors find a potential association between SARS-CoV-2 mutations and CD8 T alterations to implicate possible contributions of CD8 T cells in evasion of SARS-CoV-2 from host immunity.

Here, using cryo-EM and biochemistry, the authors delineate how the XPD helicase unorthodoxly uses its Arch domain to separate double-stranded DNA upon approaching a DNA lesion, promoting our understanding of NER bubble formation and damage verification.

CD19 CAR-T cells have achieved some success in treating myeloma patients despite the limited detection of the CD19 antigen. Here, the authors show using dSTORM that 10/14 myeloma samples studied express ultra-low levels of CD19, which are sufficient for engaging CAR-T cells in vitro.

Gain of function mutations in isocitrate dehydrogenase 1 (IDH1) have been detected in cases of acute myeloid leukemia (AML). The application of an allosteric IDH1 inhibitor in AML cells promotes blast differentiation and restores DNA cytosine methylation patterns.

The surface area of living cells is tightly regulated. Here, authors show that the surface area and shape of cells can be reversibly manipulated with light using amphiphilic molecular photoswitches that enter and leave the membrane.

Large language models are increasingly used for diverse tasks, yet we have limited insight into their understanding of chemistry. Now ChemBench—a benchmarking framework containing more than 2,700 question–answer pairs—has been developed to assess their chemical knowledge and reasoning, revealing that the best models surpass human chemists on average but struggle with some basic tasks.

Injury repair is characterized by the generation of transient cell states important for tissue recovery. Here, the authors present a single cell RNA-seq map of recovery from bleomycin lung injury in mice and uncover a Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis.

JN.1 lineage is a globally dominant variant of SARS-CoV-2. Here, the authors examine structural insights into the BA.2.86 and JN.1 spike dynamics to help understand the mechanisms underlying SARS-CoV-2 infection and its neutralizing-antibody evasion.

Catch bonds have a role in bacterial adhesion and infection by uropathogenic E. coli.Here, the authors report crystal structures, molecular dynamics simulations, ligand binding analysis and cell tracking to characterise the catch bond interaction between the adhesin FimH and carbohydrate receptors.

Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.

Non-invasive monitoring of solid tumour growth in mice is difficult. In this study, the authors develop a system for monitoring the secretion of luciferase either from Gaussia princeps or Cypridina noctiluca in the blood of mice harbouring luciferase-labelled tumour cells, thus providing a system to monitor two different cell populations in vivo.

Bacteria–bacteria interactions and resultant microbiota changes were characterized using a synthetic phyllosphere community in planta.

The emergence of acquired resistance to standard platinum-etoposide chemotherapy in small cell lung cancer (SCLC) is a common event. Here, the authors using paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models reveal a mechanism of drug resistance in SCLC mediated by Notch and nitric oxide activation of soluble guanylate cyclase signalling.

Hartl et al. demonstrate how metabolism and the cell cycle are coupled in prokaryotic cells by analysing the metabolome during the cell cycle in Caulobacter crescentus. Whereas the levels of most metabolites are independent of the cell cycle, glutathione fluctuates and is required for coordinated cell cycle progression.

The surfactant-like protein Ki-67 mediates the clustering of chromosomes during mitotic exit, which displaces large cytoplasmic molecules from the future nuclear space and thus enables the separation of cytoplasmic and nuclear components before the nuclear envelope reforms.

Autologous transgenic epidermal stem cell cultures are used to reconstitute almost the entire epidermis of a patient with severe junctional epidermolysis bullosa.

Dark reversion of the red-light receptor phytochrome B (phyB) converts the receptor to the inactive state. Here, Enderle et al. show that PCH1 and PCHL bind phyB and suppress dark reversion, and that far-red and blue-light induced upregulation of PCH1 and PCHL increases red light sensitivity in Arabidopsis.

Structural characterization of B6, a monoclonal antibody that cross-reacts with eight β-coronavirus spike proteins from three viral lineages, reveals a conserved cryptic epitope that could serve as a target for structure-guided design of a pan-β-coronavirus vaccine.

In DNA-PAINT, transient binding of dye-labeled oligonucleotides to their target strands creates the ‘blinking’ required for stochastic nanoscopy. This protocol describes how to apply DNA-PAINT, from sample preparation to data processing.

The authors show that binding of 14-3-3ζ enhances cytosolic Tau solubility by promoting phosphorylated Tau removal from microtubules, while simultaneously inhibiting Tau aggregation both directly and indirectly via suppression of condensate formation.

The authors provide protocols for rapid and scalable genome engineering in somatic cells of the liver and pancreas through both viral and nonviral delivery of CRISPR components into living mice.

NLRP10 has been considered as an inflammasome inhibitor. Here the authors show that upon mitochondrial rupture, NLRP10 assembles a canonical inflammasome and is highly expressed in differentiated keratinocytes, possibly supporting skin homeostasis.

The ABL-ERK-MYC signaling axis inhibits WIPI1 gene expression, thereby controlling the autophagy-enhancing effect of WIPI1 in the context of C. elegans lifespan control.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.