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Hepatitis C virus remains a health burden due to the lack of an effective vaccine, hindered by difficulties in replicating the native E1E2 antigen structure. Here, the authors engineer a stabilized E1E2 heterodimer using cryo-EM-guided modifications, enhancing immunogenicity and paving the way for future HCV vaccine development.

RNA polymerase II (RNAPII) is typically considered as an essential enzyme. Here the authors show that natural degradation of RNAPII drives chromatin reorganization in growing oocytes, preparing the chromatin for genome activation after fertilization.

Exposure to inflammation drives hematopoietic stem cells (HSC) aging, limiting their self-renewal capacity and differentiation. Here, the authors explore the mechanistic link between inflammation and HSC aging. Using mouse models, they identify the innate immune RNA sensor MDA5 as a key mediator of HSC aging and show that MDA5 loss ameliorates the aging phenotype by improving proteostasis in aged HSCs.

CRISPR–Cas9 in Streptococcus pyogenes prevents self-cleavage through abasic CRISPR RNA oxidations that suppress off-target activity. Inspired by a natural mechanism, Gu and Kim et al. designed chemically modified abasic guide RNAs to enhance genome-editing specificity of SpCas9, suppressing off-target toxicity in in vivo applications.

Although river protection is core to social and environmental well-being, the extent to which river conservation policies are effective is difficult to assess. This study reveals that, under all relevant protection mechanisms in the contiguous USA, only 12% of rivers are adequately protected.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

C-prenylated flavonoids possess notable pharmaceutical potential, but their production is hindered by the challenging selective prenylation of their unstable polyphenolic cores. Here, the authors present a directed evolution strategy to reshape the active pocket of the prenyltransferase AtaPT, uncovering an aromatic cage that governs both regioselectivity and donor specificity, and achieve efficient and scalable synthesis of 27 C-prenylated flavonoids.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

Bång-Rudenstam et al. report that the acidic tumour microenvironment facilitates the assembly of chondroitin sulfate-enriched glycocalyx to disrupt lipid scavenging and prevent ferroptosis, thereby providing an adaptive mechanism upon tumour acidosis.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Taniuchi and colleagues show that differential phosphorylation of the terminal Y residue in Runx proteins connect MHC restriction with the helper versus cytotoxic T cell lineage choice.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

In a phase 1 trial, personalized mRNA vaccines tailored to individual tumour mutations in triple-negative breast cancer induced robust, long-lasting T cell responses and improved prognosis.

Coronaviruses use suboptimal codons yet efficiently translate proteins. Here, the authors show that SARS-CoV-2 and HCoV-OC43 infections reprogram four host tRNA modifications, linking stress-induced tRNA remodelling to enhanced viral translation.

Microscopic imaging and biochemical studies show that sinuses in mouse and human form a highly dynamic surface that regulates fluid movement and immune cell surveillance via RAMP1-dependent regulation of smooth muscle contraction and RAMP2-dependent regulation of the sinus endothelial barrier.

Battery electrode binders are hard to image but strongly affect battery performance. Here, authors use silver and bromine staining to reveal common cellulose- and rubber-based binders in graphite and Si negative electrodes and identify processing that reduces electrode resistance.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

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.

Rapid immune activation requires tight control of mRNA stability in CD8⁺ T cells. Here, the authors show that a compositive RNA motif – m⁶A sites positioned next to AU-rich elements - marks mRNAs for rapid decay during activation, revealing a coordinated mechanism that shapes T-cell immunity.

CRISPR/Cas9 screens have identified genetic contributions to many phenotypes. However, studying combinations of genes or regulatory elements remains challenging. Here, the authors use CRISPR/Cas12a to overcome those challenges and enable new approaches to study combinatorial genetic mechanisms.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

Most pachytene PIWI-interacting RNAs (piRNAs) have no biological function; however, a small population enhances sperm fitness, which has led to their persistence in mammalian evolution.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Epigenetic traits can persist across generations through small RNAs and chromatin marks. Here, the authors show that SET-24, a non-enzymatic SET protein, partners with HCF-1 to maintain RNAi silencing and sustain chromatin states and small RNA populations in C. elegans.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

Here, the authors present a bioinformatic pipeline to annotate lncRNA genes in Aspergillus fumigatus. The majority of these lncRNAs are only conserved at the species level, and their expression is highly responsive to antifungal exposure in Aspergillus fumigatus.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

A low thermal expansion chromium alloy overcomes inherent brittleness via atomic faulting in layered precipitates. This tough, corrosion-resistant material enables stable components for extreme environments.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

Spectroscopic observations of the ultra-hot Jupiter WASP-189b reveal both volatile (H₂O, CO, OH) and refractory (Fe, Mg, Si) gas in its atmosphere. Here, the authors show that the abundance ratio of refractory species reflects that of the host star.

Large biospecimen banks are limited by a lack of fast, flexible, database-like retrieval. Here, authors encode metadata as DNA barcodes on silica-encapsulated samples and demonstrate numerical range, categorical, and Boolean queries, enabling rapid, precise recall from pooled DNA/RNA archives.

The study shows that incorporating information on pre-existing moisture conditions into the atmospheric river scale improves early-warning identification of flood-generating events.

Most kiwifruit species are vulnerable to high levels of heat stress. Here, the authors report natural variation at the GATA transcription factor binding site of EGY3 gene mediates chloroplastic ROS homeostasis to confer kiwifruit thermotolerance.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Crohn’s disease is associated with disturbances in the B-cell compartment and secreted antibodies. Here, the authors reveal impaired colonic dimeric IgA responses in patients with Crohn’s disease and verify this phenotype in murine models, demonstrating that mitochondrial dysfunction drives defective mucosal humoral immunity.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

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.

DNA methylation heterogeneity and dynamics hinder distinguishing early pathological changes from normal variation. Here, the authors identify stable sites whose disruption is linked to blood cancers, aging, and cardiovascular risk.

Japonica subspecies has a lower nitrogen use efficiency (NUE) than that of indica rice. Here, the authors show that natural variations in the NIN-like protein 4 (OsNLP4) encoding gene are responsible for the divergence and introgression of the indica OsNLP4 allele into elite japonica cultivar can increase NUE and grain yield.

The open interfaces of a three-dimensional all-dielectric photonic topological insulator operate as effective metasurfaces with helical surface states, enabling spin-dependent steering and directional control of far-field surface state emission.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Amundsen Sea records show warm Circumpolar Deep Water drove major West Antarctic Ice Sheet retreat from 18,000–10,000 years ago. Subsequent cooling stabilized the grounding line, indicating ocean heat—not atmospheric warming—controlled long-term WAIS change.

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.