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Gene editing technologies enable precise DNA modifications but remain limited by efficiency, precision of intended edits, and flexibility. Here, authors develop chimeric oligonucleotide-directed and Cas polymerase-based systems that enhance programmable gene correction across cells and embryos.

Kancharla, Kelly et al. identify an acridone antimalarial potent across all major parasite life stages. Lead candidate T111 shows oral efficacy, low toxicity, and synergy with tafenoquine, providing a unique mechanism to overcome resistance.

Yashinskie, Zhu and colleagues show that p53 activation triggers increased synthesis and accumulation of phospholipids, with enhanced activation of autophagy and lysosomal catabolism programmes and increased reliance on lipid headgroup recycling.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

In vivo adenine base editing corrects a common Pex1 pathogenic allele in mouse models of Zellweger spectrum disorder, rescuing liver pathology, fatty acid levels, body weight and peroxisome function.

Here, by integrating host gene expression and airway microbiome data, the authors distinguish true lower respiratory infection from incidental pathogen carriage, and identify biologically distinct patterns that improve diagnostic precision beyond pathogen detection alone

Climate of the last 2.5 million years is simulated, showing good agreement with proxy data, and identifying CO2 and ice feedbacks, rather than direct orbital forcing, as the primary causes of global temperature change.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Key papers on the role of nutrition and metabolic cues in puberty timing were published in 1963, and there have been many advances in this field in the subsequent 60 years. This Review discusses the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development.

An improved strategy for siting food and energy production is needed to avoid further habitat loss. This paper presents a multi-sector framework that can empower land use planners to find synergies across conservation and development sectors.

Wang, Wilfahrt and colleagues show that phosphoethanolamine, a phospholipid intermediate, is enriched in tumour interstitial fluid and induces T cell dysfunction, in part by depleting diacylglycerol and dampening T cell receptor signalling.

An in vitro toolkit for studying VSG diversification defines key molecular requirements underlying the formation of mosaic VSGs, providing an experimental framework for the exploration of antigen diversification in Trypanosoma brucei and in other pathogenic microorganisms.

It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

The authors show that mitochondria can chronically hyperpolarize under normal or disease conditions and be induced by environmental exposures. This triggers phospholipid remodeling, which in turn affects the epigenome to regulate transcription.

Tumour expression profiling is currently used for prognostic and predictive purposes without taking into account the intra patient heterogeneity. Here the authors show that cancer cell specific signatures overcome the tumour heterogeneity effect and result in better classification of colorectal cancer patients.

Retinitis pigmentosa is a genetic disease causing degeneration of retinal pigment epithelial and photoreceptor cells. Here, the authors show that PNPLA6 regulates choline metabolism for retinal homeostasis, and its dysfunction leads to degeneration, which can be rescued by choline supplementation.

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

Fetal brain development is dependent on the maternal supply of long chain polyunsaturated fatty acids (LC-PUFAs). Here, the authors show that pregnancy-induced liver-X-receptor (LXR) signaling in the maternal liver promotes the synthesis of LC-PUFA-containing phospholipids for export to the fetus.

Various intrinsic factors, including the metabolic state of cancer cells, govern their ability to evade immune destruction. Here the authors show that inactivation of dihydroorotate dehydrogenase (DHODH), an enzyme in the pyrimidine synthesis pathway, increases the sensitivity of cancer cells to T cell cytotoxicity through CDP-Choline dependent induction of ferroptosis.

Gut microbial changes promoted by weaning in mice result in epigenetic modification in intestinal stem cells with long-lasting impact on host immunity.

Coupling an optogenetic lipid-modifying enzyme with proximity labeling reveals protein networks and mechanisms regulating lipid homeostasis in the membranes of target organelles.

Lazarevic et al. reveal a shared loss of a TBX5-dependent atrial gene network in cardiomyocytes and a disease-specific network gain in activated fibroblasts across atrial fibrillation and heart failure models.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Here, the authors present the cryo-EM structure of yeast CPT1, a critical enzyme in phospholipid synthesis, identifying residues crucial for substrate preference. This enable a reaction mechanism for the family of CDP-alcohol phosphotransferases to be proposed.

Expression quantitative trait loci (eQTL) analysis in patients with inflammatory bowel disease identify potential target genes for IBD GWAS loci not readily detected in individuals without disease highlighting the importance disease-focused studies.

Human mutations in PCYT2 result in severe pathology with failure to thrive and progressive degenerative disease. Cikes et al. demonstrate that loss of PCYT2-synthesized phosphatidylethanolamines in muscle impairs sarcolemmal lipid bilayer stability and mitochondrial homeostasis, leading to muscle degeneration and premature ageing in mice.

Previously uncharacterized cysteine-derived conjugates, including with endogenous sugar metabolites, accumulate in cancer cells with constitutive NRF2 activation and account for some of the increased cystine uptake that cannot be explained by conventional cysteine metabolism.

The authors developed a microfluidic device, FIND-Chip, designed to automate and enhance oocyte recovery from follicular fluid, a process traditionally done manually. When used in clinical settings, the device recovered additional oocytes missed during manual screening, substantially increasing the number of viable oocytes available for in vitro fertilization.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.