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The synthesis of unprotected C-heteroaryl glycosides is challenging because of the lack of methods to utilize native saccharides as substrates. Now these compounds, capped as redox-active glycosyl sulfide donors, undergo C–C coupling with N-heteroarenes through a photoinduced, thiyl radical-mediated reaction with control over the chemo-, site- and stereoselectivity.

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.

Electron hopping in geometrically frustrated lattices can result in a rich variety of unusual behaviours. Now, the orbital arrangement in a van der Waals metal with a non-frustrated, primitive lattice is found to show similar effects.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Synapse dysfunction contributes to cognitive decline with age. Here, the authors show that aging-related changes in microglia and the extracellular matrix are associated with synapse abundance, extracellular matrix buildup, and cognitive deficits in aging mice.

Confocal microscopy enables high-resolution, high-plex 3D cyclic immunofluorescence of 30- to 50-µm-thick tissue sections. The approach allows for rich phenotypic assessments of intact cells and intercellular interactions with subcellular resolution.

Here, the authors demonstrate the electrical tunability of the nonlinear interactions, ultrafast formation and decay dynamics of layer-hybridized excitons in a field-effect device based on natural homobilayer MoS₂.

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.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Emerging materials between molecules and materials demand new modeling approaches. Here, the authors present a localized active space approach that enables accurate and efficient band structure calculations to capture long-range charge and energy transfer in correlated materials.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

During SARS-CoV-2 infection caspase-8 fuels harmful inflammation independent of apoptosis. Genetic loss of caspase-8 reduces cytokine levels, lowers viral load and mitigates disease severity, revealing non-apoptotic caspase-8 as a key driver of severe COVID-19.

Becker et. al developed a proteomic proximity labeling platform named POCA, which makes use of a photosensitizer for singlet oxygen production and protein capture in the presence of amine, enabling profiling of interactomes of proteins and lipids in living cells.

Using cryo-electron tomography, Lopez-Robles, Scaramuzza, Astorga-Simon, Ishida et al. solve the architecture of ESCPE-1, a protein scaffold that mediates the recycling of cargo from endosome to trans-Golgi network and plasma membrane in tubular carriers.

Barcoding aids in the optimization of lipid nanoparticles. Here, the authors report on multiplexed mRNA barcoding that enables high-resolution spatiotemporal profiling of lipid nanoparticles, linking accumulation kinetics to functional delivery and revealing zonal liver targeting.

Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.

A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Forests are essential for both climate change mitigation and biodiversity conservation, yet how to balance these goals in managed forests remains unclear. Here, using a Europe-wide dataset, the authors find that biodiversity increases with carbon stocks, but mostly when deadwood is included.

Liquid methane lakes dot Titan’s polar regions. Numerical models reveal that the creation of buoyant bubbles through nitrogen exsolution near the bed of the Ligeia Mare lake can explain transient brightenings observed by Cassini on the lake’s surface.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

APOBEC deaminases restrict retroviruses but can also mutate human DNA. Here, the authors show that cancerassociated APOBEC3s with low RNA binding, known to enter the nucleus, are selectively recognized by E3 ligases and degraded, eliminating harmful nuclear enzymes, and limiting genome mutation.

Rearrangements govern many properties of materials and molecules, but it has been largely unexplored how to create flexible structures from the bottom up. Here, the authors use colloidal particles to explore how to guide the kinetic self-assembly pathways into ordered structures that maintain flexibility.

Cancer patients are at increased risk for severe bacterial infections due to immune dysfunction. Here, the authors show that chronic tumor-derived G-CSF drives NAMPT/NAD-dependent neutrophil dysfunction from the progenitor stage, and that targeting this pathway restores infection control.

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.

Evolution selects for the fittest but must operate within the realm of the physically possible. Here, the authors present a theoretical framework that allows them to explore how ten abiotic constraints can shape the operation, regulation, and adaptation of metabolism in E. coli.

cSplotch compares spatial transcriptomics data across ages and regions of mouse colon tissue.

Electrocatalytic CO₂ reduction is typically studied at laboratory scale under ambient conditions; however, temperature and pressure may have a profound impact on the mechanism of this reaction and on its relevance to industrial applications. This study uses a custom temperature- and pressure-adjustable cell to reveal a chain growth mechanism emerging on copper electrodes at elevated temperatures and pressures.

Mitochondria play roles in sensing environmental and physiological stress, but their response can become maladaptive during chronic stress. Here they identify a protective miRNA response in C. elegans that maintains tissue health by attenuating mitochondrial stress signaling.

Laser-based micro-focused angle-resolved photoemission spectroscopy reveals both fractionalized and marginal quasiparticles in C₃-symmetric electron pockets near the Brillouin zone centre of the ferromagnetic kagome metal Fe₃Sn₂.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Chan and colleagues report that tumor ecosystem and microbiome features are associated with response to anti-PD-L1 avelumab plus chemoradiotherapy in patients with locally advanced head and neck cancer.

Here, the authors systematically map metaproteomic responses of ex vivo human gut microbiota to common therapeutics, identifying several drug classes inducing strong disruptions to the microbial ecosystem, providing a comprehensive view of how drugs influence gut microbiome function and ecology at the protein level.

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.

Pangenomic and epidemiological analyses reveal a genetic shift in U.S. Salmonella Hadar populations during 2019–20, driven by expansion of a lineage carrying a prophage-like element that likely arose in commercial poultry and spread to backyard flocks.

Human immunodeficiency virus (HIV)-associated gut microbiome dysbiosis correlates with systemic immunodeficiency and opportunistic gut infections. Faecal microbiome transplantation from people living with HIV with high peripheral CD4⁺ T cell counts improved intestinal immunity and protection against Cryptosporidium parvum in mice.

Interferometric imaging based on phase-sensitive OCT in living rat eyes demonstrates electromechanical deformation of the rod outer segment associated with reversible isomerization of rhodopsin, providing a new assay for studying visual transduction.

External Control Arm methods for clinical trials were developed to compare the efficacy of a treatment to a control group that is built with data from external sources. Here, the authors present FedECA, a privacy-enhancing method for analyzing treatment effects across institutions, streamlining multi-centric trial design and thereby accelerating drug development while minimizing patient data exposure.

Scaffold-guided bone regeneration is a promising treatment strategy for segmental defects, but clinical translation has been hindered, partially by mechanical function limitations. Here, Clark et al. describes a permanent printed polymer with a resorbable stem cell laden ceramic core for reconstructing segmental mandibular defects, which is tested in an ovine model.

Regeneration varies dramatically even between closely related species. Here they show that the evolutionary loss of foot regeneration observed in Hydra oligactis stems from weak Wnt activation after injury. Transient Wnt activation restores foot regeneration and the expression of foot transcription factor dlx2.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Mapping of spatial metabolic gradients in the mouse liver and intestine identifies fructose-induced focal derangements in liver metabolism.

The second sound is an entropy oscillation propagating with constant pressure. Here the authors demonstrate the variation of the second sound wave in the crossover from the Bose-Einstein condensate to the Bardeen-Cooper-Schrieffer superfluid using 6Li.

JWST observations suggest that both pebbles and planetesimals played an important role in forming the giant exoplanet WASP-121 b beyond the H₂O ice line. They also indicate that strong vertical mixing likely drives the nightside atmospheric chemistry.

The interplay between neuronal activity and tumor progression is well-established. Here, the authors demonstrate that blockade of β-adrenergic signaling via administration of propranolol suppresses lung metastasis in multiple mouse tumor models by enhancing the accumulation of cytotoxic CD4 T cells while reducing CCR2+ monocytes, highlighting the re-purposing of β-blockers as a valid therapeutic approach for cancer treatment.

Squeezed light field microscopy (SLIM) combines ideas from tomography and compressed sensing with light field microscopy to enable volumetric imaging at kilohertz rates, as demonstrated in blood flow imaging in zebrafish and voltage imaging in leeches and mice.