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Neuropathic pain is commonly treated with opioids due to limited alternatives. Here, authors determine cryo-EM structures of the neuronal glycine transporter GlyT2 and develop a reversible inhibitor that provides analgesia in vivo without side effects.

The chemistry of phosphaalumenes featuring multiple bonds between phosphorus and aluminum remains largely unexplored. Here the authors report the synthesis of a phosphaalumene and characterize its activation of small molecules.

T cell activation requires major metabolic adaptation. Here authors find that in mice and humans, expression of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1) increases in CD4+ T cells upon activation, particularly within the cytoplasm, which impacts NADP/H and reactive oxygen species signalling, restraining activation and cytokine production while promoting CD4 + T cell survival during viral and fungal infections.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

People constantly decide whether to stop what they are doing to do something else. Here, the authors show that the quality of available options has a greater influence on people’s decisions to help others than to help themselves.

Long COVID is associated with challenges in energy management, with limited interventions available. In this study, a just-in-time app-based energy management intervention for long COVID did not reduce postexertional malaise compared to usual care, though both groups improved over time, showing the approach was safe but not effective.

A vascular graft enables wireless, real-time and continuous stenosis diagnosis and management.

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 contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

Avian influenza jumped from wild birds into dairy cattle. Here, the authors report that two mutations in the viral polymerase helped the virus to quickly adapt to cattle. Mutations increased the polymerase activity and made the virus better at replicating in human cells.

Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.

The authors developed an LXR inverse agonist, TLC-2716, and show it is effective in reducing triglycerides and cholesterol in dysmetabolic preclinical models. Additionally, a phase 1 trial in healthy participants shows that TLC-2716 is well tolerated and reduces plasma triglycerides and postprandial remnant cholesterol, highlighting its potential for managing cardiovascular risk.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Mitochondrial dysfunction in dopaminergic neurons is a pathological hallmark of Parkinson’s disease. Here, the authors find a conserved mechanism by which a single transcription factor controls mitochondrial health in dopaminergic neurons during the aging process.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

In this study, the authors model the current mechanical properties of the seafloor of Jupiter’s icy moon Europa, and find those rocks to be too strong to allow the kind of fracturing that, on Earth, enables rock–water chemical reactions on which chemosynthetic life relies.

Mitochondrial damage is a central pathological mechanism of cerebral ischemia-reperfusion injury. This study develops a bioengineered nanolamellar system to sequentially restore neuronal cell mitochondrial function and modulate microglial polarization to mitigate ischemia-reperfusion injury.

Wafer bonding has allowed the synthesis of twisted interfaces which support polar discontinuities in ferroelectric lithium niobate. Two-dimensional sheet conductivity arises but is suppressed when twist angles lead to interfacial lattice aperiodicity.

Single-neuron recordings in humans reveal largely separate content and context neurons whose coordinated activity flexibly places memory items in context.

The authors discover a tissue-scale fitness sensing mechanism in the lung, where mesenchymal Yap antagonizes epithelial Yap to dictate epithelial cell fate. This inter-tissue cell competition orchestrates lung architecture and lung disease.

This study identifies 245 genetic loci associated with head-to-body ratios using 38,202 bone density scan images from the UK Biobank, revealing genetic links to skeletal and brain development, disease susceptibility, and human evolutionary adaptation.

Genome-wide association studies (GWAS) of deep learning-derived measurements of aortic valve function, along with multitrait analyses incorporating disease-based GWAS, identify 166 genetic loci associated with aortic valve function or aortic stenosis.

Mauthe et al. find that protein aggregate clearance requires fragmentation of the aggregate by a chaperone module and a proteasomal regulatory particle for recruitment and clustering of selective autophagy receptors to initiate phagophore formation.

This Review surveys how higher-order interactions, which link more than two units at a time, reshape collective dynamics in complex systems. New synchronization phenomena, analytical frameworks and emerging methods to reduce or infer higher-order structure from data, are highlighted.

A broad systems-level approach is necessary to understand the intricate etiology of clinical complications from atherosclerotic cardiovascular disease. Here, the authors reconstruct a causal network of circulating proteins and identify subnetworks linked to future risk of myocardial infarction and other cardiometabolic traits.

The authors show that in mice the glucocorticoid receptor is essential for caloric restriction to rewire stress hormone action and gene regulation to boost circadian rhythms, reprogram metabolism and promote healthy aging

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

Stroke affects the brain in complex, highly individual ways. Here, the authors show that applying generative and causal AI methods to routinely collected brain scans may enable more closely personalized treatment recommendations.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

The tightly closed conformation of the Spike helps SARS-CoV-2 evade the immune system. This cryptic conformation is shaped by increased mannosidic glycosylation and furin cleavage shielding conformational epitopes enable virus to persist in the presence of neutralizing antibodies.

This study shows that high-molecular weight tau has enhanced seeding capacity, and seeding differences can define molecular subtypes of progressive supranuclear palsy, underpinning the disease’s heterogeneity.