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Targeted ablation of prostaglandin E₂ (PGE₂) signalling in CAR T cells enhances their activity in PGE₂-rich solid tumours, with demonstrations of efficacy in vitro, in mouse xenografts and in patient-derived organotypic tumour spheroids.

Soft electrostatic actuators are crucial for advancing robotic systems that require adaptability and safety in unstructured environments. This study introduces ultralight soft electrostatic actuators utilizing solid-liquid-gas architectures, achieving significant improvements in power-to-weight ratio and actuation speed, exemplified by a 60% increase in jump height in a jumping robot compared to traditional designs.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Bartonella bacilliformis, a bacterium endemic in South America, causes the deadly Oroya fever, marked by massive red blood damage. This study identifies that porin A and α/β-hydrolase are important bacterial proteins in driving this hemolytic process.

Our understanding of chromosome organization and dynamics in spherical bacteria, such as Staphylococcus aureus, remains limited. Here, the authors show that chromosome replication and cell division cycles are not synchronized in S. aureus, with cells exhibiting two segregated origins of replication at the start of the cell cycle.

Surgical adhesions are organ-joining bands of scar tissue that remain clinically untreatable. Here, the authors show that adhesions are formed through expansive mesothelial membrane bridges, and that blocking these with small molecules prevents formation of adhesions in mice.

Here, the authors present a new method for isolating methanogenic archaea from human fecal samples and establish stable archaeal cultures yielding nine previously uncultivated strains, which upon further genomic and functional analyzes suggest may be potentially associated with gastrointestinal diseases.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Fatty liver disease exacerbates atherosclerosis, but the underlying mechanisms remain unclear. Here, the authors show that D-dopachrome tautomerase (D-DT/MIF-2) acts as an atypical chemokine, promoting both atherosclerosis and hepatic lipid accumulation.

By individually replacing 16 yeast genes encoding ABC transporters by GFP, mating and selecting for strains with accumulated mutations the authors create a Green Monster, a strain with deletions in all 16 genes.

Imaging of muscle fibrosis with a handheld device could potentially serve as a biomarker for disease progression and response to therapy in patients with Duchenne muscular dystrophy.

Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

Constructing a minimal protein machinery for self-division of membrane compartments is a major goal of bottom-up synthetic biology. Here, authors achieved the assembly, placement and onset of contraction of a minimal division ring in lipid vesicles.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Boos et al. show that impairing mitochondrial protein import induces a global transcriptional response to activate the ubiquitin–proteasome system and heat stress response and repress oxidative phosphorylation genes.​

piRNAs are small RNA molecules found primarily in the testes of mice and men. Stallmeyer et al. demonstrate that variants in specific genes can disrupt the formation of piRNAs, impairing spermatogenesis and causing human male infertility.

RNA base editing enables a precise, reversible and doseable change of genetic information. Here, authors propose base editing as a method to control post-translational modifications via removal of regulatory phosphorylation and acetylation sites, applying the approach to modulation of the JAK/STAT pathway via editing of wildtype alleles.

Metal-organic frameworks are versatile materials but typically suffer from poor electrical conductivity. Here, a patterning technique allows controlled metal-organic framework growth on predefined areas of functionalized carbon nanotube for increased conductivity.

A nucleofection-based method to enable efficient gene editing of primary human resting CD4⁺ T cells.

This protocol enables ex vivo immunocapture of cell-type-specific mitochondria directly from their tissue context in heterogeneous tissues such as the nervous system, using MitoTag reporter mice.

After myocardial infarction, dedifferentiated cardiomyocytes secrete the protein Reg3β, thereby recruiting macrophages required for neutrophil clearance and myocardial healing.

Light-based modulation of the microtubule (MT) cytoskeleton is an attractive goal for spatiotemporally-resolved MT studies. Here the authors develop a first generation photoswitchable small molecule MT stabiliser based on paclitaxel, allowing optical control over cellular MT dynamics.

Innate lymphoid cells (ILC), including natural killer (NK) cells, are important innate immune regulators. Here the authors show that, in human infant intestines, CD103⁺Eomes⁺ NK cells are the predominant ILC population, but are replaced gradually by Eomes⁺ T cells, while NKp44⁺ NK cells persist in adult intestines.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Lifespan can be affected by both physiological ageing and specific sets of pathologies associated with old age. Here the authors report a resource of large-scale cross-sectional phenotyping of aging male mice at different time points to analyse a large set of phenotypes and molecular markers, including during genetic and diet interventions affecting lifespan.

Cancer-associated fibroblasts (CAFs) are a major component of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDA). Here the authors report the importance of macrophage-derived Oncostatin M in reprogramming CAFs to drive a pro-tumorigenic environment in PDA.

The development of specific anti-cytokine/chemokine therapeutic strategies for atherosclerotic disease is challenging. Here, the authors have designed a peptide-based ectodomain mimic of the chemokine receptor CXCR4 that selectively targets MIF but not CXCL12 and blocks experimental atherosclerosis in vivo.

RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

Anaerobic archaea enriched in thermophilic microbial consortia completely degrade butane by modifying mechanisms which were hitherto thought to be specific to methane metabolism.

Characterization of xylan utilization loci in the butyrate-producing Firmicute Roseburia intestinalis provides mechanistic insight into its growth on different xylan substrates and its ability to co-grow and compete with a xylan-degrading commensal from the Bacteroides genus.

The bacterial insertase BAM is a key target for novel antibiotics that are urgently needed. Here, we describe the implementation of an assay that allows screening for BAM inhibitors in the native membrane in high-throughput format.

Illness signals from the gut reactivate and strengthen flavour representations in the amygdala to support learning from delayed postingestive feedback.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .

Epsilonproteobacteria, such as Sulfurospirillum, can use molecular hydrogen as an electron donor for respiration. Here, the authors show that Sulfurospirillum can, in addition, release hydrogen during fermentation, allowing metabolic interactions with other hydrogen-consuming microorganisms.

Excitatory input onto inhibitory interneurons in the developing mouse cortex acts through PTEN to protect interneurons from cell death and thus regulate the balance between excitation and inhibition.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

The open-source Single Cell Genotyper software addresses common artifacts in single-cell sequencing data in order to robustly infer clonal genotypes, enabling the study of tumor heterogeneity and evolution.

Sohrab Shah, Samuel Aparicio and colleagues analyze whole genomes and single cells from ovarian cancers in the peritoneal cavity to establish patterns of disease spread. They determine the clonal relationships between multiple tumor sites and characterize the migratory potential of genomically diverse clones.

The ASAP4 family of genetically encoded voltage indicators allows recording of action potentials and subthreshold activity with either one- or two-photon microscopy over extended periods of time.

Here the authors perform a high-throughput screen to identify compounds that stimulate or repress the splicing of neuronal microexons. One of these compounds rescues the splicing of several microexons in the brains of mice haploinsufficient for Srrm4.