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TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

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.

Integrating complex multi-omics data for individual patient decision making can be challenging. Here, the authors develop Knowledge Connector as a decision support system to generate and document Molecular Tumor Board recommendations and support medical decision-making.

The study presents a recyclable polymer system that stores solar energy and releases it as hydrogen on demand, offering an efficient and sustainable route for renewable energy storage and fuel generation.

Natural product–inspired compounds are primed to interact with and manipulate biological processes, but obtaining these complex molecules poses synthetic challenges. The development of a 12-step, 1-pot cascade reaction leads to the 'centrocountins', tetrahydroindoloquinolizines that modulate mitosis by targeting the centrosome-associated proteins nucleophosmin and Crm1.

In the phase 1/2 CASTLE basket trial, autologous CD19 CAR-T cell therapy in patients with treatment-refractory systemic lupus erythematosus, systemic sclerosis or idiopathic inflammatory myopathy was safe, with improved disease activity and patient-reported global health in most patients.

Chronic tinnitus is often treated with cognitive-behavioural therapy, hearing aids, counselling, or sound therapy, but their combined benefit is unclear. Here, the authors show, in a multicentre randomised trial, that combination treatments improve tinnitus scores more than single therapies, though benefits appear compensatory rather than synergistic.

We show that FOXF2 maintains cerebrovascular function through Tie2 signaling, and that pharmacological activation of Tie2 with AKB-9778 rescues deficits in cerebral small vessel disease and stroke.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Pertpy serves as a one-stop and performant framework for single-cell perturbation data analysis.

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

Platelets are known to have functions beyond those in thrombosis and haemostasis. Here the authors use multi-colour flow cytometry and proteomics to analyse platelet phenotypes in psoriatic disease and proteins that are potentially involved in the interaction of platelets with immune cells.

Diamond colour centres are of interest for solid-state quantum technologies but obtaining an efficient spin-photon interface remains challenging. Here, the authors use resonant excitation under magnetic fields to optically access the electronic spin sublevels of silicon-vacancy centres in diamond.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, but its spike protein doesn’t efficiently bind human ACE2. Here, the authors show that exchange of spike residue 403 between RaTG13 and SARS-CoV-2 spike proteins affects binding to human ACE2 and entry of pseudotyped viruses.

Highly pathogenic avian influenza H5N1 viruses cause mass mortality in birds and have infected over 50 mammalian species, including humans. Here, the authors report the use of a propagation-defective vesicular stomatitis virus replicon vaccine in captive birds, which provides protection against lethal H5N1 challenge.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Tracers are fluorescent protein ligands required for various displacement assays. Here, the authors announce a curated database named tracerDB, which will make essential tracer data, contributed by the worldwide research community, easily available and searchable.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

CD123 expression on leukemic stem and progenitor cells (LSPCs) and leukemic blasts representing a promising therapeutic target. However previous CD123-targeting approaches had limited efficacy and safety concerns. The authors here evaluate the bispecific CD123/CD16A innate cell engager AFM28 and manifest its efficacy both in vitro and in vivo, which is mediated by NK cells.

The products and dynamics in mutual neutralisation of \({{{{\rm{O}}}}_{2}}^{+}\) with O⁻ occurring in atmospheric sprites are unknown. Here, the authors reveal a dissociative two-step mechanism via intermediate Rydberg states and a dependence on the \({{{{\rm{O}}}}_{2}}^{+}\) vibrational state.

The wheat Pm3 immune receptors confer resistance against powdery mildew by recognizing isolate-specific avirulence (AVR) effectors of the pathogen. Here, the authors identify and characterize two new AVR genes and demonstrate that Pm3 receptors are determinants of host-specificity for grass mildews.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.

Causal and mechanistic modelling strategies, which aim to infer cause–effect relationships, provide insights into cellular responses to perturbations. The authors review computational approaches that harness machine learning and single-cell data to advance our understanding of cellular heterogeneity and causal mechanisms in biological systems.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Dynamic control of components is required for large-scale quantum photonic networks. Here, Kapfingeret al. show dynamic control of the interaction between two coupled photonic crystal nanocavities forming a photonic molecule. Tuning is achieved by using an electrically generated radio frequency surface acoustic wave.

The experimental investigation of relaxation times in graphene quantum dots has long been hindered by the limited tunability of these devices. Here Volk et. al.employ a device design to study this problem and report charge relaxation times of around 60–100 ns.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Gonzalez-Gallego et al. developed a fully iPS-cell-based human three-dimensional blood–brain barrier (BBB) model and used it to study roles of the stroke risk gene FOXF2 in BBB dysregulation, demonstrating its applicability for mechanistic research and drug development.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Climate change affects agricultural productivity. New systematic global agricultural yield projections of the major crops were conducted using ensembles of the latest generation of crop and climate models. Substantial shifts in global crop productivity due to climate change will occur within the next 20 years—several decades sooner than previous projections—highlighting the need for targeted food system adaptation and risk management in the coming decades.

Prions are infectious agents that initiate transmissible spongiform encephalopathies. The study demonstrates that Prion proteins lower cellular oxidative stress via GPX8, remodel membrane lipids, and together with RAC3, sensitize cells to ferroptotic death, highlighting new therapeutic targets in prion diseases.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Authors present both preclinical data in mice and clinical data from humans in support of the hypothesis that stress negatively affects bone growth and repair. These effects are mediated by neutrophil-derived catecholamines inhibiting cartilage-to-bone transition via β2-adrenoceptor signaling in chondrocytes.

Advances in electron microscopy are enabling ever smaller features to be probed, with the measurement of atomic electric fields standing as a major challenge. Towards that aim, Müller et al.present a simplified theoretical approach for enhancing the resolution in differential phase contrast microscopy.

In atrial fibrillation patients, circulating biomarkers reflecting inflammation, myocardial injury, and coagulation improve prediction of stroke, heart failure, and bleeding, outperforming clinical scores and enhance risk stratification.”.

The accuracy of melanoma diagnosis can vary considerably among clinicians, impacting both patient outcomes and the performance of related AI tools. Here, the authors systematically assess interrater variability among expert pathologists reviewing histopathological images and clinical metadata of melanoma-suspicious lesions collected at eight German hospitals.

Comparative Physicochemical Profiling (CPP), an interpretable machine learning algorithm, identifies physicochemical signatures of γ-secretase substrates, capturing features hidden in sequences and enabling proteome-wide prediction of substrate recognition.