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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.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Surface acoustic waves have previously been used, in conjunction with electric currents and assisting magnetic fields, to manipulate magnetization. Here, Rivelles, Yanes, and coauthors succeed in driving magnetic domain walls solely with surface acoustic waves, an important milestone in acoustically controlled spintronic devices.’

Long-read sequencing enables high-quality genome assemblies, but challenges remain. Here, the authors introduce Cornetto, a method that improves assembly quality, enables genome sequencing from saliva, and accurately resolves medically-relevant repetitive genes.

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.

Here the authors provide the experimental demonstration of a widely tunable integrated frequency comb source unlocking the spectrum from the visible to the mid-infrared in a thin-film lithium niobate platform.

Bacterial ribonucleoprotein bodies are dynamic biomolecular condensates that play roles in RNA metabolism. Here, Ortiz-Rodríguez et al. show that, under stress, these condensates shift from a liquid state to a rigid state and switch their function from mRNA decay to mRNA storage, thus enabling transcript preservation and rapid recovery upon nutrient replenishment.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

A galvanic strategy enables the intercalation of diverse molecular cations into bulk and few-layer van der Waals crystals under mild conditions, yielding 50 organic–inorganic superlattices. This method enables the definition of vertical and lateral intercalation heterostructures, opening avenues for the device integration of hybrid quantum materials.

Experimental systems in which non-trivial topology is driven by spontaneous symmetry breaking are rare. Now, topological gaps resulting from two excitonic condensates have been demonstrated in a three-dimensional material.

Transition metal dichalcogenides exhibit diverse and tunable electronic states. Here the authors reveal a cascade of phase transitions upon increasing hydrostatic pressure in the few-layer 1T’-WS₂, including a re-entrant superconducting phase emerging from a normal state exhibiting anomalous Hall effect.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The interplay between electronic topology and superconductivity is of great current interest in condensed matter physics. Here, the authors unveil an unconventional two-dimensional superconducting state accompanied by a van Hove singularity in the recently discovered Dirac nodal line semimetal ZrAs₂, which is exclusively confined to the top and bottom surfaces.

The symmetry and mechanism underlying unconventional charge orders in Kagome materials are under debate. Here, the authors uncover a longitudinal and helicity-dependent photocurrent in KV₃Sb₅ that indicates broken symmetries and intrinsic chirality.

Drug molecules operate through physical interaction with specific cellular targets, and understanding this interaction is important for mechanisms and the potential therapeutic effect of drug candidates. Here, the authors show that bioluminescence resonance energy transfer can be used to monitor the intracellular engagement of a drug with its target.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Constrained catecholamines gain β₂AR selectivity. Although the orthosteric pockets are identical in β₁AR and β₂AR, surrounding residues allosterically modify the pockets and contribute to the β₂AR selectivity of the constrained catecholamines.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Topologically protected hinge modes could be important for developing quantum devices, but electronic transport through those states has not been demonstrated. Now quantum transport has been shown in gapless topological hinge states.

Understanding the structural basis for the inhibition of archaeal eukaryotic-like RNA polymerases (RNAPs) during virus infection is of interest for drug design. Here, the authors present the cryo-EM structures of apo Sulfolobus acidocaldarius RNAP and the RNAP complex structures with two regulatory factors, RIP and TFS4 that inhibit transcription and discuss their inhibitory mechanisms.

The prodrug gliocidin effectively kills glioblastoma cells by targeting de novo purine synthesis, improving survival in mouse models.

In a phase 1 trial, patients with pancreatic ductal adenocarcinoma who were treated with surgery and bespoke neoantigen mRNA vaccines combined with anti-PD-L1 and chemotherapy exhibited marked long-lived persistence of neoantigen-specific CD8⁺ T cell clones, which correlated with prolonged recurrence-free survival at a 3.2-year follow-up.

The pairing mechanism in kagome superconductors is still not fully understood. Now, CsV₃Sb₅, which belongs to this family, is shown to have orbital-selective pairing with two distinct superconducting domes that are not separated by any phase boundary.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

Klunk and colleagues identify signatures of natural selection imposed by Yersinia pestis and demonstrate their effect on genetic diversity and susceptibility to certain diseases in the present day.

IL-33 induces tertiary lymphoid structures.

The oncometabolite D-2-HG has been implicated in compromising DNA repair pathway. Here the authors show D-2-HG leads to genome-wide DNA hypermethylation and loss of CTCF coverage, which impairs the assembly of the homologous recombination DNA repair machinery and associated topology adjustment.

The accuracy of metagenomic DNA sequencing is limited by environmental DNA contamination. Here, the authors develop and test SIFT-seq, a metagenomic DNA sequencing assay that allows to identify and remove environmental DNA contamination introduced during sample preparation.

This study assessed COVID-19 social science preprints’ replicability using structured groups. Both beginners and more-experienced participants used a elicitation protocol to make better-than-chance predictions about the reliability of research claims under high uncertainty.

A hybrid topological phase of matter is discovered in the simple elemental-solid arsenic and explored using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis.

Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.

Anti-ferromagnetic based memories have a wide range of advantages over their ferromagnetic counterparts, however, their electrical signatures of switching are complicated by spurious signals. Here, Arpaci et al demonstrate an experimental method to distinguish between anti-ferromagnetic switching, and such spurious signatures.

Genome assemblies of 13 domesticated and wild rice relatives reveal salient features of genome evolution across the genus Oryza, especially rapid species diversification and turnover of transposons. This study also releases a complete long-read assembly of IR 8 ‘Miracle Rice’.

Variant detection in problematic genes is facilitated with a curated benchmark.

3D brain atlases enable spatial data integration across studies. Here, the authors present the Developmental Mouse Brain Common Coordinate Framework, a 3D multimodal atlas from embryonic to adult ages for cell type mapping through brain development.

In this mouse study, an adenine base editor shows potential as a durable therapy for glycogen storage disease type-Ia, correcting both the life-threatening lack of blood glucose control and metabolic abnormalities of this orphan disease.

Lung adenocarcinoma is often curable when diagnosed at an early stage, but a subsection of patients will progress. Here, the authors use multi-omics profiling to show that gene expression data can predict clinical outcome.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

Replacing the toxic lead in the state-of-the-art halide perovskite solar cells is highly desired but the device performance and stability are usually compromised. Here Chen et al. develop inorganic cesium tin and germanium mixed-cation perovskites that show high operational stability and efficiency over 7%.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations.