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RNA design aims to find a sequence that folds into a target structure. Here, the authors formulate it as a continuous optimization over a coupled-variable distribution and leverage sampling to optimize arbitrary objectives. On Eterna100, it outperforms state-of-the-art methods across key metrics.

The study develops a printable concrete using cellulose nanofibers and limestone filler, enhancing rheological and mechanical properties while reducing cement content. It demonstrates improved buildability and sustainability, with potential for large-scale 3D printing applications in construction.

Many vascular‑disease risk loci lack defined causal genes. Here, the authors integrate functional genomics and CRISPR screens to identify genes influencing smooth muscle cell behaviour, validating roles for FES, BCAR1, CARF and SMARCA4, with Fes loss promoting atherosclerosis and hypertension.

The herpes simplex virus lytic-latent balance is incompletely understood. In this study, the authors show that it is controlled by the relative abundance of host activating and repressive forkhead box (FOX) transcription factors that recruit epigenetic cofactors to the viral genome to remodel viral chromatin.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Chemical modifications on DNA are key regulators of epigenetic function. Here, the authors develop 6-base-CUT&Tag to simultaneously profile multiple DNA and chromatin features on the same DNA fragment. This work reveals how specific DNA and histone marks colocalise at different enhancer regions.

The role of the innate immune system in pancreatic cancer is largely unexplored. Here, the authors reveal a targetable cancer cell-intrinsic axis in pancreatic cancer comprising ASC inflammasome complexes that link innate immunity with mitochondrial function and metabolism.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A Kitaev chain formed by two quantum dots coupled via a superconductor support the so-called poor man’s Majorana bound states. Here, the authors form a minimal Kitaev chain using Yu-Shiba-Rusinov states and show that the resulting bound states are more robust than in the case of unproximitized quantum dots.

The authors demonstrate a nanoscale particle-exchange heat engine using a diradical molecule coupled to superconducting electrodes. By driving a phase transition into the Yu-Shiba-Rusinov regime, they achieve a fivefold boost in thermoelectric power, enabling advances in cryogenic heat recovery and quantum cooling.

GGC repeat expansions causing oculopharyngeal myopathy with or without leukoencephalopathy are located in small open reading frames and translated into polyglycine proteins that form cellular aggregates, driving neuronal and muscle cell dysfunction.

Producing valuable hydrocarbons electrochemically from carbon monoxide (CO) is an energy-efficient pathway, but reliance on costly pure CO as a feedstock limits its economic viability. This article shows that abundant CO-rich syngas can be directly used to synthesize ethylene.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

An optical archival storage technology based on femtosecond laser direct writing in glass addresses the practical demands of archival storage.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

The emergence of resistant subpopulations often underlies the development of resistance to cancer therapy. Here, using a DNA barcoding approach, the authors demonstrate EGFR TKI treatment in non-small cell lung cancer enriches for resistant subpopulation which can be prevented by treatment with the multikinase inhibitor sorafenib via inhibition of MKNK, STAT3 and MCL1.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

DNA hybridisation thermodynamics parameters underlie rational design of oligonucleotides for diagnostics and nanotechnology. Here, the authors present an accurate method to measure the free energy of a given DNA structure at specific temperature and buffer conditions.

Electrochemical CO reduction to multi-carbon products offers a carbon-negative approach to produce chemicals, but the intricate reaction pathways lead to a broad spectrum of products. Now it has been shown that alkali cations alter the mechanistic pathways that govern the reaction selectivity involved in the formation of hydrocarbons versus oxygenates.

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.

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.

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.

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

Single iron atoms on nitrogen-doped carbon catalysts are a promising alternative to platinum for the oxygen reduction reaction on fuel cell cathodes, but commonly suffer from low stability. Here an in situ chemical vapour deposition synthetic approach is presented, enabling high iron active site dispersion and reducing surface porosity, which mitigates demetallation and carbon corrosion, ensuring high activity and stability.

A protein biomarker, the NOTCH3 extracellular domain, identifies individuals with idiopathic pulmonary hypertension, correlates with disease progression, improves mortality risk prediction and provides a readily implementable, noninvasive blood test for this disease.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

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.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

HIV remission of more than 6 years was achieved in a patient with functional viral co-receptors after CCR5 wild-type/Δ32 allogeneic stem cell transplantation, providing evidence of other mechanisms that can be harnessed to attain long-term remission.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

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.