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A wearable that continuously measures the concentration of a drug is demonstrated in humans.

CRISPR–Cas9 in Streptococcus pyogenes prevents self-cleavage through abasic CRISPR RNA oxidations that suppress off-target activity. Inspired by a natural mechanism, Gu and Kim et al. designed chemically modified abasic guide RNAs to enhance genome-editing specificity of SpCas9, suppressing off-target toxicity in in vivo applications.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

The authors found that the Alzheimer’s disease-associated protein tau, widely considered pathogenic when hyperphosphorylated, has a natural function as part of the innate immune system in the brain and can protect against herpes simplex virus 1.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

The mantle upwelling beneath the Afar rift may be influenced by tectonic processes in the overriding lithospheric plates that shape the distribution of both the compositional heterogeneities and abundance of melt, according to a geochemical and statistical study of volcanic samples.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

To humanize models of liver metabolic disease research, authors develop a microfluidic platform leveraging human hepatic spheroids integrated with microvasculature and circulating monocytes to model hepatic insulin resistance.

This report describes a nanobody targeting glycine receptor mGlyR that inhibits its ability to regulate G protein signaling and produces anti-depressant effects in mice providing an immunotherapy approach to potentially treat depression.

Analysis of Babesia divergens egress from host cells reveals druggable targets and identifies compounds for potential babesiosis treatment.

Although the resolution achievable with cryo-EM can now rival crystallography, its application to small protein assemblies remains challenging. Here the authors demonstrate the use of the Volta phase plate for single particle analysis and its potential for the study of small specimens.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

Cystine levels in pancreatic ductal adenocarcinoma (PDAC) tumour microenvironment are deficient, despite its crucial role for cancer cell maintenance. Here, the authors show that adaptation to cystine limitation stress promotes PDAC growth through induces metabolic reprogramming to promote PDAC tumor growth, while conferring a vulnerability in lipid metabolism targetable by lomitapide.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Optical spin orientation of itinerant ferromagnets in twisted MoTe₂ homobilayers is demonstrated, enabling control of topological Chern numbers with circularly polarized light.

Yoshioka et al. show that bacteria wrap their flagella to squeeze through near cell-width confinements, which allows symbiotic microbes to navigate constricted gut regions within insect hosts.

Mouse models demonstrate that vagal sensory neurons transmit signals from lung adenocarcinoma to the brain, increasing sympathetic efferent activity in the tumour microenvironment and thereby creating a immunologically permissive environment for tumour growth.

How leptin signalling produces anti‑obesity effects is incompletely understood. Here, the authors demonstrate that FAK and PYK2 are required for STAT3 activation, normal leptin responses, and HDAC6 inhibitor‑mediated weight loss, with their loss causing hyperphagic obesity.

Genes encoding key epigenetic regulators, including Lysine Demethylase 6A (KDM6A), are frequently mutated in bladder cancer. Here, the authors show that loss of KDM6A promotes formation of extrachromosomal circular DNA (eccDNA), genomic instability, and metabolic reprogramming, driving resistance to cisplatin chemotherapy while simultaneously enhancing sensitivity to immune checkpoint inhibitors.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

Self-assembled monolayers are efficient hole-selective contacts but suffer from aggregation and adhesion issues. To address these, Wang et al. introduce a dimeric molecular design that forms a hydrogen-bond network, enabling 28.4% certified efficiency in all-perovskite tandem solar cells.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Cas12a3 nucleases constitute a distinct clade of type V CRISPR–Cas bacterial immune systems that preferentially cleave the 3′ tails of tRNAs after recognition of target RNA to induce growth arrest and block phage dissemination.

While CDK4/6 inhibitors (CDK4/6i) are often initially successful in many breast cancer subtypes, often resistance develops and other subtypes like triple-negative breast cancer (TNBC) fail to respond. Here, the authors demonstrate that the CDK2 inhibitor BLU-222, alone or with CDK4/6i, restores cell-cycle control via p21/p27 induction overcoming resistance in preclinical models of breast cancer, including TNBC.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

Measles virus and canine distemper virus (CDV) are still causing health impairments in humans and animals. Here, the authors develop a synthetic antibody protecting ferrets from lethal CDV infections, providing a roadmap for antiviral drug design.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Using a non-human primate model, the authors identified the tissue sites of initial viral rebound after discontinuation of antiretroviral therapy, demonstrating that such rebound preferentially occurs in the gastrointestinal tract-associated lymphoid tissues.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Laboratory automation, machine learning, and metabolic engineering may be combined to quickly and efficiently build productive microbial strains. Here the authors used these techniques in P. putida to boost isoprenol titers 5-fold over six DBTL cycles while sampling a reduced design space.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

Lipid nanoparticle based mRNA vaccines are known to induce robust CD4 + T cell responses. Here the authors establish a role of endogenously derived antigen processing in the optimal priming of CD4 + T cell responses to mRNA lipid nanoparticle vaccines.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

Unusual mechanical properties can be obtained with careful design of metamaterials. Here, Davami et al. use a microscale periodic cellular design to create plate mechanical metamaterials which exhibit ultralow mass per unit area, enhanced bending stiffness and ability to recover after extreme deformations.