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Protein function is governed by more than abundance alone. Here, the authors introduce a supercharging-enhanced nDIA-MS workflow to map drug-induced solubility changes across the proteome, enabling high-throughput analysis of protein state transitions.

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.

A population genomic analysis of 1,854 Listeria soil isolates collected across the contiguous United States identifies geographically prevalent phylogroups with increased pangenome openness and recombination, as a result of adaptation to variable environments.

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.

Intramolecular coupling of extended biphen[n]arenes is developed to yield cycloparaphenylenes (CPPs). The modular nature of biphen[n]arenes makes it possible to customize CPP structures, which permits tuning of their photophysical properties. The syntheses are short and excellent yields are achieved. Moreover, postsynthetic functionalization is possible.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Polariton interferometry reveals flat-band ultrastrong coupling between phonons and surface plasmon polaritons over a large wavevector range.

Electrocatalytic CO₂ conversion offers opportunities for producing sustainable fuels and chemicals, but achieving strong performance with realistic CO₂ sources remains a challenge. Here a system is designed to use high-pressure captured CO₂, and achieves 85% Faradaic efficiency and high-purity C₂H₄ for over 1,500 h.

Antarctic Bottom Water progressively filled more of the deep Southern Ocean through the last deglaciation, potentially contributing to the increase in atmospheric CO₂, according to neodymium isotope records from the Weddell–Enderby Basin.

Deterministically generated single photons are useful for quantum communications, but the processes that create such light are often non-deterministic. Here, the authors enhance the single-photon output probability by multiplexing photons from four temporal modes using fibre-integrated optics.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

Composites of carbon nanotubes and superconductors provide technologically important new, or improved, functionalities. Here, with a chemical solution approach, well-aligned carbon nanotube forests embedded in a superconducting NbC matrix are shown to effectively enhance the superconducting properties of NbC.

This study present a strategy involving construction of 22,821 photovoltaic, onshore-wind, and offshore-wind plants in 192 countries worldwide under cost minimization, emphasizing the physical and socioeconomic challenges forward.

Chiral antiferromagnets, such as Mn3Pt, host a variety of transport phenomena arising due to the chiral arrangement of the spins. Herein, the authors find two contributions to the anomalous hall effect in Mn3Pt, and through comparison with other chiral antiferromagnets develop a universal scaling law for the anomalous hall effect in chiral antiferromagnets.

Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor subtype preference.

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.

The results of the Fifth RNA-Puzzles contest highlights advances in RNA three-dimensional structure prediction and uncovers new insights into RNA folding and structure.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

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.

A magnetic-spectrometer-free method for electron–proton scattering data reveals a proton charge radius 2.7 standard deviations smaller than the currently accepted value from electron–proton scattering, yet consistent with other recent experiments.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Induced proximity by molecular glues is a strategy that leverages the recruitment of proteins to facilitate their modification or degradation. Here the authors present unbiased quantitative proteomic, biochemical and computational workflows that uncover hundreds of CRBN molecular glue targets using recombinant protein and cell lysate.

A computational model called Centaur, developed by fine-tuning a language model on a huge dataset called Psych-101, can predict and simulate human nature in experiments expressible in natural language, even in previously unseen situations.

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.

Tirofiban is an inhibitor of platelet αIIbβ3 which may contribute to venous thrombosis. Here the authors developed a non-agonizing modified tirofiban, defined by its cryo-EM structure bound to platelet αIIbβ3 and elucidated the pathogenic role of αIIbβ3 in venous thrombogenesis.

External Control Arm methods for clinical trials were developed to compare the efficacy of a treatment to a control group that is built with data from external sources. Here, the authors present FedECA, a privacy-enhancing method for analyzing treatment effects across institutions, streamlining multi-centric trial design and thereby accelerating drug development while minimizing patient data exposure.

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

Organic semiconductors are attractive candidates for spintronics applications because of their long spin lifetimes. But few studies have investigated how to optimize the injection of spin into these materials. A new study suggests that the metal/organic interface is key.

As a ‘safe’ alternative to harmful monomeric halogenated flame retardants, the use of polymeric flame retardants has surged in recent years. The authors show that polymeric flame retardants break down in the environment into small toxic molecules that can pose environmental hazards.

Traditional photonic crystals consist of periodic media with a pre-defined optical response. Here, the authors combine nanostructured back-gate insulators with a continuous layer of graphene to demonstrate an electrically tunable two-dimensional photonic crystal suitable for controlling the propagation of surface plasmon polaritons.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

The authors analyze genetic correlations and perform Mendelian randomization to reveal bidirectional links between major depressive disorder and various traits, highlighting its role as an important risk factor across medical, functional and psychosocial domains and identifying potential causal relationships.

The lymphotoxin (LT) system has several defined roles in the regulation of immunity as well as vascular and lymphatic biology, however its role in cancer is less understood. Here the authors show that regulatory T cell-derived LTα1β2 promotes LTβ receptor-nonclassical NFκB signaling in tumor cells and lymphatic endothelial cells, accelerating tumor growth and metastasis.

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.

SARS-CoV-2 S protein prematurely refolds to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yield. Here, Juraszek et al. present a stable SARS-CoV-2 S-closed protein variant with increased expression and correct folding, predominantly in closed prefusion conformation.

Polyploidy and subsequent post-polyploid diploidization (PPD) contribute to evolutionary success of plant species. Here, using 11 genomes from all nine subfamilies of Malvaceae as an example, the authors provide evidence to support the “polyploidy for survival and PPD for success” hypothesis.

The death of massive stars has traditionally been discovered by explosive events in the gamma-ray band. Liu et al. show that the sensitive wide-field monitor on board Einstein Probe can reveal a weak soft-X-ray signal much earlier than gamma rays.

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.

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.

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.

Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

The development of the efficient catalyst in the direct H2O2 synthesis (DHS) from H2 and O2 remains a formidable challenge. Here, the authors develop a two-step approach to prepare a layer of Pd oxide on PdSn nanowires which displays superior reactivity in the DHS at zero Celcius.

Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics’ Precivity AD test for Aβ42 and Aβ40. Compared to white individuals, Black individuals had higher average plasma Aβ42/40 levels at baseline, consistent with a lower average level of amyloid pathology.

Presence of peritoneal metastasis is associated with a decreased survival in patients with colorectal cancer. Here, the authors show that peritoneal-resident macrophages promote the formation of an immunosuppressive environment that facilitate peritoneal metastasis in colorectal cancer.

Multivalent display of integrin antagonists enhances their efficacy, but current synthetic scaffolds used to display ligands are limited in range and precision. Englundet al. develop a new scaffold to study the multivalent effects of integrin antagonists across wide ranges of ligand number, density, and 3D arrangement.