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Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

Smc5/6 association with DNA junctions can support genomic functions. Here, the authors show that Smc5/6 junction polarity preferences, targeting, and dwell times are determined by its structural modules as well as the RPA and PCNA genomic factors.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

A 15-year prospective cohort study found that during times of social unrest in Hong Kong, people experienced more conflicts with family and friends and this coincided with the use of social media—these factors were also associated with higher levels of depression.

Activin receptor-like kinase 4 (ALK4) is frequently downregulated or mutated in cancers. Here the authors find that ALK4 loss promotes canonical TGF-β signaling and cancer progression through increasing TGF-β receptor N-linked glycosylation and subsequently stabilizing these receptors at the cell surface.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

In this work, authors present their goal-directed subgroup identification (GD-SI) framework, reconciling biological heterogeneity with clinical actionability, and offering a scalable infrastructure for precision trial design and personalized sepsis management.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Using crystallography and in planta analysis, Shahul Hameed et al. reveal how ROS-induced disulphide bonding inhibits the strigolactone-degrading enzyme CXE15, uncovering a redox-sensitive mechanism for regulating hormone catabolism in plants.

AIRES (algorithmic iterative reticular synthesis) is an integrated cycle combining automated synthesis, image recognition, single-crystal X-ray diffraction and algorithmic decision-making to maximize the discovery of distinct crystal structures. Demonstrated on zeolitic imidazolate frameworks, AIRES offers a systematic and efficient blueprint for reticular synthesis, with broad implications for accelerating materials discovery.

A wearable human–machine interface combines inertial and electromyography sensors with deep learning to robustly extract gesture signals and enable real-time robotic control under diverse motion artefacts in dynamic environments.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

EuIn₂As₂ is a candidate as an axion insulator, a material that can host axion-like quasi-particles, in direct analogy with the axion proposed in particle physics to resolve the so called “strong CP problem”. Here Soh et al., perform resonant elastic X-Ray scattering on EuIn₂As₂ and show that the magnetic order consists of commensurate chiral magnetic structures, satisfying the symmetry requirements for EuIn₂As₂ to be an axion insulator.’

Preparing room temperature phosphorescent materials from biomass is important but challenging. Here, the authors report the use of liquid monomer 2-hydroxyethyl acrylate for dissolution of lignin and subsequent solvent-free preparation of lignin-based RTP materials.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

In this study, the authors combine interpolation techniques and deep learning methods, introducing Interpolating Neural Networks (INNs) to model complex systems with high accuracy and low computational cost.

Commensal Candida albicans enhances the virulence and dissemination of Salmonella enterica subsp. enterica serovar Typhimurium.

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.

Convenient and sustainable photoactivated room temperature phosphorescent (RTP) materials exhibit great potential in a wide ranging of applications but are difficult to obtain. Here the authors develop a photoactivated RTP materials by covalently attaching lignin to polylactic acid.

It is elusive to manufacture room temperature phosphorescent (RTP) materials through effective and ambient processing approaches. Here the authors report the production of photocured RTP materials using lignosulfonate to act as RTP chromophore and photoinitiator, achieving easy preparation, low cost and good performance.

iExoKras^G12D are engineered exosomes for the delivery of siRNA targeting KRAS^G12D. Here the authors describe the results of a phase I trial of iExoKrasG12D in patients with metastatic pancreatic cancer, reporting safety and clinical activity, as well as immunological correlates informing on tumor immune microenvironment reprograming and future combination with immune checkpoint inhibitors.’

A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them.

Organic materials potentially offer a low-cost, flexible and environment-friendly route to spintronics. Here, the authors demonstrate an organic spin-valve device in which an electric field can control both the magnitude and the sign of magnetoresistance.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

The authors develop a strategy that allows the diffusion limit of ions in water to be approached for large-area, free-standing, synthetic membranes using covalently bonded polymer frameworks with rigidity-confined ion channels.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

When a superconductor is in contact with a normal metal, Cooper pairs from the superconductor ‘leak’ into the metal, causing local superconductivity. When in contact with a ferromagnet, however, Cooper pairs do not stray very far. Therefore, the discovery that a ferromagnetic nanowire goes completely superconducting when placed between two superconducting electrodes is surprising indeed.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Single-photon sources with a single-photon efficiency of 0.60, a single-photon purity of 0.975 and an indistinguishability of 0.975 are demonstrated. This is achieved by fabricating elliptical resonators around site-registered quantum dots.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Wamaitha and colleagues used the rhesus macaque to characterize the transcriptional and spatial mechanisms underlying ovarian reserve formation in prenatal life providing insights into the molecular processes governing ovarian follicle establishment.

Base lesions can be directly repaired by oxidative dealkylation catalysed by AlkB in bacteria and by ABH2/ABH3 in man. Several structures of AlkB and ABH2 bound to dsDNA are solved. These structures reveal why AlkB prefers ssDNA to dsDNA substrates, and how ABH2 differs structurally, to allow it to repair dsDNA.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

The transcription factor Wilms’ tumour 1 (WT1) regulates kidney development, and Wt1 mutations are associated with renal cancer. Here the authors identify WT1 target genes in renal progenitors during early kidney development in mouse embryos and show that loss of Wt1suppresses FGF and induces BMP signalling.

The search for low-dimensional condensed matter platforms that host correlated electronic states has recently revolved around kagome lattices. Here, the authors evidence kagome-like bands in a 2D coloring-triangle lattice with a semiconducting bandgap.

Carbon coating of electrodes is a common way to enhance electrochemical activity, but the interface mechanism is unclear. Here, Wang et al. adopt a molten technique to produce a sample with large flat surface, which enables visualization of the electrode size-dependent interface change during coating.

The Fermi-LAT Collaboration reports a significant γ-ray detection (5.2σ) from the coronae of radio-quiet active galactic nuclei, revealing compact (~10 gravitational radii) and extended (~2.7 × 10⁶ gravitational radii) corona regions, challenging existing models.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.