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The authors describe the discovery of a series of potent non-competitive allosteric inhibitors of the ZIKV NS2B-NS3 protease, which exhibit antiviral activity in vitro and robust oral efficacy against ZIKV infections in a mouse model.

Conventional slurry electrodes limit high-energy lithium batteries. This work shows that dry-processed electrodes with molecularly coupled carbon–binder networks enable high mass and active material loading, supporting stable high-voltage operation and enhancing battery energy density.

Vestibular schwannomas that are caused by genetic mutations in the NF2 gene are hard to treat and lead to hearing loss. Here authors show in a mouse model that faithfully represents the human condition that combination therapy with anti-PD-1 and anti-VEGF inhibits tumor growth via normalizing the tumor vasculature and enhances T and NK cell antitumor cytotoxicity via upregulation of NKG2D.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

Here the authors report that using an “isogenomic” reference genome (fully matched to the experimental cell line) improves the accuracy of genomic, epigenomic and transcriptomic analyses, as well as genome editing, compared to a non-matched generic reference.

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

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.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

DBiTplus represents an integrated experimental and computational workflow that unifies sequencing-based and imaging-based spatial omics, demonstrated by combining transcriptomic profiling and multiplexed protein imaging on the same tissue section.

Two main acceleration mechanisms in the auroral acceleration region are electric potential and Alfvénic acceleration but associated energy dynamics are not completely resolved. Here, the authors show that Alfvén waves power the Earth’s auroral arc through a static potential drop in the auroral acceleration region.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

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.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The rapid expansion of agricultural irrigation raises concerns about exacerbating water scarcity, but land–atmosphere interactions are often overlooked. This study isolates irrigation impacts from other drivers using a multi-model framework to reveal that historical irrigation expansion substantially reduces net atmospheric water influx, intensifying drying trends and accelerating terrestrial water storage depletion, urging immediate mitigation strategies.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

The authors present a diploid reference-quality genome assembly of the widely used cell line RPE-1, revealing heightened variation between haplotypes and other human genomes at centromeres. The availability of a reference genome matching the cell line under study promises a new era of high-precision haplotype-resolved functional genomics.

Authors use data from Togo to model onchocerciasis infection trends and elimination probabilities. Both ivermectin and vector control led to marked prevalence decline. Some areas may reach elimination by 2030 but others need alternative strategies.

The recent global mpox outbreaks underscore the critical need for antiviral development, hindered by the complexity of the MPXV genome. Using yeast TAR cloning, CRISPR-Cas9, and Lambda Red recombination to engineer replication-defective MPXV, the authors offer a platform for therapeutic research and identify G243-1720, a compound with a tecovirimat-like mechanism, as a promising anti-poxvirus compound.

Machine learning is increasingly used to support IVF pretreatment prognostic counseling. Here, the authors find that center-specific models improved IVF live birth predictions over a US registry model, and draw conclusions for improving IVF access, affordability and patient-centric counseling.

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.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

Sepsis may progress into lethal septic shock, but the cellular mechanisms are still unclear. Here the authors show that, in septic mice, platelets activate perivascular mast cells to cause systemic hypotension and vascular pathology, while inhibiting platelets or mast cell activation suppresses septic shock induction, thereby implicating potential therapy targets.

A variant of the OAS1 gene, which encodes an enzyme that is critical for the innate immune response to viral infections, is associated with decreased risk of death in patients with COVID-19.

Genome-wide analysis in individuals of African ancestry identifies a nonsense variant in CD36 associated with increased risk of dilated cardiomyopathy (DCM), partly accounting for the higher incidence of DCM in African-ancestry populations.

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.

Combining multiomic datasets from adolescent and middle-aged-to-older population cohorts with a purposefully devised analytical framework, we revealed substantial heterogeneity in brain-chronotype-behavior patterns and their complex interactions with everyday life.

Most quantum technologies rely upon quantum wires to ensure the faithful transfer of quantum states between remote locations—a process that is especially vulnerable to decoherence. Yao et al.propose a means to harness topological protection to design a quantum wire that is intrinsically robust against decoherence.

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.

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.

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.

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.

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.

A facile and cost-effective synthesis of MXenes is not yet available. Here, the authors propose a one-pot molten salt-based method of MXenes synthesis from elemental precursors in an air atmosphere. Li-ion storage properties of the MXenes are also reported and discussed.

Accurate modelling of memristor dynamics is essential for the development of autonomous learning in artificial neural networks. Through a combined theoretical and experimental study of the polarization switching process in ferroelectric memristors, Boynet al. establish a model that enables learning and retrieving patterns in a neural system.

Interatomic Coulombic decay (ICD) is a relaxation of an atom in a weakly bound environment by the transfer of excess energy to ionize the neighbouring atom. Here the authors observe intra-Rydberg ICD in neon clusters, which is a decay that involves the ionization of Rydberg atoms in the cluster.

Spin defects in 2D materials offer practical advantages for quantum sensing over their 3D counterparts. Here, the authors demonstrate quantum sensing under high pressure using boron vacancy centers in hBN placed inside a diamond anvil cell and use it to detect both stress gradient inside the pressure chamber and pressure-induced magnetic phase transitions.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.