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Ethanol production from CO2 electroreduction is hindered by poor carbon–carbon coupling and competing ethylene formation. Here, the authors develop a ZnO1-x-shield copper catalyst that stabilizes Cu+ species and enables efficient and selective electrochemical ethanol synthesis.

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.

Glioma stem-like cells (GSCs) contribute to therapeutic resistance via enhanced capability of DNA damage repair. Here the authors identify that the upregulated transcription factor AATF in GSCs modulates the stability and release of XRCC4 protein to promote DNA repair and resistance to radiotherapy.

Profiling nuclear N⁶-methyladenosine (m⁶A) modifications revealed enrichment of m⁶A on nuclear RNAs derived from chromosome pericentromeric γ satellite DNA II (GSATII), which regulates GSATII transcription and influences chromosome segregation during mitosis.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

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.

The MLL complex promotes androgen receptor signaling and drives growth of castration resistant prostate cancer

This study reveals the structural basis of collagen processing by the KOGG complex, revealing how it catalyzes lysine hydroxylation and dual-glycosylation, essential for collagen folding and stability, with implications for collagen-related diseases.

Solid polymer electrolytes suffer from limited ionic conductivity and poor interfacial stability for lithium batteries. Here, authors propose a fluorinated ether diluent to reduce the dipole-dipole interaction of ionic solvate with the polymer matrix and induce the formation of aggregates.

A unified framework is presented that integrates observed spatial patterns of individual trees in forests with ecological processes into a novel coexistence theory.

Enhancing the arsenal of E3 ligases is important for PROTACs development. Here, the authors identify a non-inhibitory aptameric ligand to CRL2^ZYG11B E3 ligase, and develop a general, modular, and straightforward aptamer-based PROTAC platform, termed ZATAC, providing insights for untapped E3 ligases.

Rieske oxygenase chemistry is important for biochemical pathways, but it remains elusive how a common protein scaffold can be predictively tuned to catalyze divergent reactions. Here, the authors report a strategy that can rationally tune TsaM, a Rieske monooxygenase to catalyze dioxygenation and sequential monooxygenation reactions, and customize the reactivity of other Rieske oxygenases.

Hydrogels are essential for stem cell-based tissue regeneration but struggle with hard tissue repair. The authors report a shell-hardened macroporous hydrogel with spatiotemporally programmed mechanics to enhance stem cell-driven bone regeneration.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

An electrocatalyst mediator system in which CoO_x-cluster-decorated IrO₂ activates the NO₃^- mediator into a reactive radical that abstracts a hydrogen atom from benzylic C-H is presented. This approach enables the electrochemical conversion of toluene to benzaldehyde with high Faradaic efficiency.

Targeted IKZF2 degradation represents a potential therapeutic strategy for cancer immunotherapy. Here, the authors described the discovery of PVTX-405 as a potent, highly selective, and orally efficacious IKZF2 molecular glue degrader and their preclinical data support the clinical development of PVTX-405.

The lack of generalizability and reproducibility of machine learning models in medical applications is increasingly recognized as a substantial barrier to implementing such approaches in real-world clinical settings. Highlighting this issue, Jie Cao et al. aim to reproduce a recent acute kidney injury prediction model, and find persistent discrepancies in model performance in different subgroups.

A reanalysis of the Voyager 2 flyby of Uranus shows that it occurred during an extreme compression of the planet’s magnetosphere by the upstream solar wind. This would have had significant effects on the measurements made during the flyby.

Collagen requires complicated modifications for proper assembly. Here, the authors show the structural basis of human collagen processing by the P3H1/CRTAP/PPIB complex, revealing a ‘face-to-face’ catalytic site configuration, collagen binding sites, and transition between trimer and hexamer states.

Myeloid cell subsets are playing important roles in antitumour immunity, and genes affecting their functions are potential targets for immunotherapy. Here authors show that genomic deletion of Pikfyve in CD11c⁺ cells results in tumour growth inhibition via enhanced antigen presentation and priming of antigen-specific CD8⁺ T cells in a mouse tumor model.

This study provides structural insights into human AE3’s role in pH regulation in excitable tissues, highlighting its structural differences from AE2 in anion transport regulation and their sensitivity to inhibitors.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

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.

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.

Clinical exome and transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site, as part of the Michigan Oncology Sequencing (MI-ONCOSEQ) Program.

Glucocorticoid resistance is partly due to epigenetic alterations, but the regulatory mechanisms driving these remain poorly understood. Here, a link between the activity of a lineage-specific transcription factor PU.1 and epigenetic modulators mediating the response to glucocorticoids is described in acute lymphoblastic leukemia.

Researchers unveiled the structural details of sphingomyelin synthase (SMSr), shedding light on its role in sphingolipid biosynthesis. SMSr transfers the phosphoethanolamine from PE to ceramide, adding complexity to the field of lipid homeostasis.

Some cancer patients first present with metastases where the ___location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

CRISPR screen identifies coactivators of the androgen receptor (AR) complex, including NSD2. NSD2 contributes to AR cistrome reprogramming during prostate cancer progression, and its degradation via a novel PROTAC reduces prostate cancer cell viability in vitro.

The genome sequences of 175 Ebola virus from five districts in Sierra Leone, collected during September–November 2014, show that the rate of virus evolution seems to be similar to that observed during previous outbreaks and that the genetic diversity of the virus has increased substantially, with the emergence of several novel lineages.

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.

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.

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.

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.