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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.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Systems of electron spins in nuclear-spin-rich hosts are gaining attention for quantum memory applications. Using spin ensemble studies, the authors propose transition metal ions in halide double perovskites as promising candidates, featuring long electron spin coherence and deterministic nuclear spin control.

In this study, the authors present an fMRI‑based signature of corticospinal connections, which predicts individual pain sensitivity, generalizes to patient cohorts, and tracks changes after brain stimulation, suggesting a biomarker to guide personalized pain care.

Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

Current long acting HIV therapies face challenges like prolonged pharmacokinetic tails, which increase resistance risk. The authors develop dimeric bictegravir prodrug nanosuspensions that sustain therapeutic levels for six months with a short PK tail, supporting safer ultra-long-acting HIV treatment.

The underlying molecular mechanisms of neuroinflammation and axonal damage in progressive multiple sclerosis remains unclear. Here, authors show proteomics results of human progressive multiple sclerosis brain tissues and found extracellular matrix proteins (annexin, S100, AHNAK families) were enriched in lesions and white matter.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

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.

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.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Cardiometabolic disease and depression often co-occur, but their multi-organ basis was unclear. Here, the authors analyse UK Biobank imaging and genetics, identifying abdomen-heart-brain networks and 43 shared loci, improving multimorbidity prediction

Lunar mare asymmetry could be explained by a higher nearside ilmenite content which would cause increased partial melting and volcanism relative to the farside, according to observations and petrological modelling of high-Ti glass impact beads in Chang’e-5 samples.

There is a lack of effective therapies for patients with non-V600E BRAF mutant cancer. Here, the authors report limited response in a phase II trial investigating the combination of binimetinib (MEK inhibitor) and encorafenib (BRAF inhibitor) for the treatment of non-V600E BRAF mutant cancer and subsequently investigate resistance mechanisms and combination therapeutic strategies in patient-derived models.

Chemoautotrophic carbon fixation is vital for evaluating permafrost carbon-climate feedback, but has been largely ignored. Here the authors find that dark carbon fixation predominates ~1/3 of the investigated thermokarst lakes on the Tibetan Plateau.

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.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

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.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Laser-induced conversion electron Mössbauer spectroscopy, which detects electrons emitted by ²²⁹Th nuclei in a thin ThO₂ sample excited by vacuum ultraviolet light, is demonstrated, opening the possibility of a conversion-electron-based nuclear clock.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

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.

Vinyard et al. present a generative method to model cell dynamics using neural stochastic differential equations that learn state-dependent drift and diffusion, outperforming existing approaches and enabling perturbation studies of development and disease.

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.

How myelin plays a role in long-range processing of disparate inputs remains elusive. Here, the authors show that myelin loss within the neocortex reduces the reliability to propagate cortical bursts across axons, causing an impaired temporal sharpening to compute sensory and cortical signals within the thalamus.

Efficient and durable energy storage is vital for renewable integration. Here, the authors design an aqueous iron-cerium redox flow battery using a universal complexing agent that enhances stability and efficiency, achieving long cycle life and high performance in neutral conditions.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

The Einstein Probe has discovered a fast X-ray transient, EP240414a, associated with a broad-lined type Ic supernova. Its unusually soft spectrum and weak jet add to the diversity of stellar deaths and suggest a previously unknown Wolf–Rayet star explosion mechanism.

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.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

Tools to identify who will develop Crohn’s disease in the future are limited. Here, the authors develop and validate a proteomics-based model that predicts disease onset up to 16 years before clinical diagnosis.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Solid-state sodium metal batteries with oxide solid-state electrolytes still face interfacial challenges. Here, authors report an electroinitiated polymerization strategy that heals interfaces, enhances stability, and enables long-life performance without external pressure.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

A transverse Peierls transition can occur when transverse acoustic phonons couple with conducting p-orbital electrons. Here, the authors observe an incommensurate transverse Peierls transition and signatures of a chiral charge density wave in EuAl₄.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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

Investigating the inner structure of baryons is important to further our understanding of the strong interaction. Here, the BESIII Collaboration extracts the absolute value of the ratio of the electric to magnetic form factors and its relative phase for e + e − → J/ψ → ΛΣ decays, enhancing the signal thanks to the vacuum polarisation effect at the J/ψ peak.