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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.

New methods for targeted covalent protein modification at low reactivity aspartates and glutamates are of high interest. Here, the authors report a technique inspired by the HaloTag technology, which employs a covalent conjugation reaction between ligands with a reactive chloroalkane linker and a specific aspartic acid, and use it to covalently modify lipoprotein chaperone PDEδ at a binding site glutamic acid.

This study finds that plastic mulch substantially increases crop yields but also contaminates soils and pollutes the environment. The authors propose biodegradable films, AI-driven farming, and policy reforms to address the productivity–sustainability trade-offs.

Papaya is a trioecious species with XX females, XY males, and XY^h hermaphrodites, and the combination of Y and Y^h chromosomes is lethal. Here, the authors identify the degeneration of the YY lethality gene on the Y chromosome as the causal balancing lethal factor that reenforces dioecy and stabilizes balanced sex ratios.

Self-oscillators are critical in various natural and engineered systems, as they enable complex collective behaviors through interactions among individual units. This study demonstrates that populations of Quincke colloids-self-oscillators whose back-and-forth motion defines both a phase and a nematic oscillation axis-can achieve a form of collective order, termed synchronematic order, characterized by hydrodynamic interactions that synchronize their oscillation phases and align their orientations.

Soil life relies on microbial nutrient exchange to maintain ecosystem balance. This study shows that cobamide-producing microbes act as essential connectors in soil food webs, supporting host health and highlighting cross-kingdom links central to One Health.

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.

In Eastern Asia, vegetation greening, especially in perennial drylands, has increasingly reduced dust emissions since the early 2000s, with effects amplified over long timescales, underscoring the mitigating capacity of land-surface change for multi-decadal dust trends.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Polygenic scores often underperform in non‑European ancestries. Here, the authors present GPTL, an R package with three transfer‑learning methods that improve cross‑ancestry PGS using either individual‑level data or GWAS summary statistics.

This study demonstrates that suppressing interfacial molecular aggregation enables highly efficient and scalable perovskite solar cells. The approach delivers over 26% power conversion efficiency, supports large-area modules, and improves operational stability.

Rearrangement of the B cell receptor is sequential, and pairing of the successfully assembled heavy chain with the surrogate light chain proteins VpreB and λ5 to form the pre-B cell receptor is an important checkpoint signal for continued B cell development. Here, the authors show that λ5 plays a key role in the multi-step assembly process involving association-induced folding reactions.

A universal approach to construct low-resistance oxide layer by multiple tunnelling paths is proposed for efficient and durable Si-based photocathode. This approach can speed up the pace of development of practical photoelectrochemical devices.

The study shows forests near edges store less carbon due to higher environmental stress. Spatial optimization of new forest plantations could boost carbon storage by 986 Tg by 2060, with 53% of the gain from reducing edge effects.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

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.

Fabricating breakthrough materials capable of desalinating seawater and brine with high selectivity and low energy consumption is vital to address the global water shortage and energy crisis. Here the authors describe the synthesis of thin films with submicron thicknesses and subnanometer pores with outstanding desalination performance.

Through integrated multi-omics and experimental validation, this study reveals that altered gut microbiota and bile acid metabolism activate TLR3 to induce urothelial injury in interstitial cystitis, identifying a pathway with therapeutic potential.

Here, the authors document the evolutionary dynamics of angiosperm pollen, using pollen morphology and time calibrated phylogeny. They identify two surges in pollen disparity in the mid-Cretaceous and Paleogene that are associated with environmental changes and important pollen adaptations.

Recent work has revealed that dendritic cells (DCs) are more heterogeneous than previously thought, yet the functional roles of these newly described DC subsets remain unclear. Here, Li et al. find that in mice, TSLP from keratinocytes activates transitional DC-derived DC2 to promote GATA3⁺ regulatory T cells and mediate immunosuppression during inflammation and cancer.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

Atomic force microscopy is used to investigate the adsorption and organization of ions on charged surfaces. Trivalent ions adopt complex networks, clusters and layers associated with overcharging, whereas divalent ions follow classical predictions.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Prior hypoglycemia alters the paracrine interaction between islet α and δ cells, leading to impaired counter-regulatory glucagon secretion through somatostatin hypersecretion, increasing the risk of recurrent hypoglycemia.

The study introduces radio interferometric multiplexed spectroscopy (RIMS), a method designed to efficiently monitor the radio emissions of massive samples of stars. Applying it to LOFAR data, the authors identify stellar bursts, offering clues to possible star–planet magnetic interactions.

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.

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.

Efficient Kr/Xe separation is crucial for high-tech industries, defense, and aerospace applications. While conventional adsorbents typically capture Xe, their application is hindered by high energy costs during desorption. Here authors present a MOF with synergistic structural dynamics and local flexibility that reverses conventional selectivity, enabling preferential adsorption of Kr at room temperature.

Tunable moiré WSe₂ bilayers realize Hubbard-model physics, exhibiting antiferromagnetism, strange metals and superconducting domes, offering a controllable platform to study high-transition-temperature superconductivity.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

This study shows that many small RNAs in Capsella rubella pollen originate from maternal tissues. These mobile small RNAs support proper pollen development, revealing that non-cell-autonomous small RNAs are crucial for successful plant reproduction.

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.

Dredging and dumping in the North Sea strongly disturb sediment and carbon fluxes, affecting coastal Blue Carbon systems. Global estimates show these activities rival natural fluxes and should be included in sediment and carbon budgets.

Anti-phased changes in Antarctic Circumpolar Current strength between the Indian and Pacific sectors of the Southern Ocean occurred on orbital timescales over the past one million years, linked to glacial cycles and obliquity forcing, according to proxy records and modelling.

The success of photocatalytic coupling of CH₄ has been limited by the low solar absorption of wide-bandgap semiconductors and the uncontrolled oxidation caused by radical oxygen species. Here a Pd/Co₃O₄ heterojunction derived from a metal–organic framework demonstrates the selective conversion of CH₄ to C₂H₆ by less reactive oxygen species under full-solar-spectrum irradiation.

Yakut communities, with Trans-Baikal admixture during the Mongol expansion, preserved genomic diversity and oral microbiomes despite the Russian conquest, which introduced cereals, pathogens and Christianity, whereas marital practices preserved low consanguinity except in one late case of traditional shamanism.

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.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

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.

Catalytic breakdown of highly persistent fluorinated pollutants is hindered by limited proton availability and catalyst degradation. This study shows that in situ proton-supplying sites enable low-temperature, long-lasting decomposition of stubborn PFAS gas.

The present study shows that maternal presence beyond early life remains crucial for brain, behavioural and physiological development in young horses, highlighting the importance of the mother–offspring relationship during a childhood-like stage.

Lakes fed by melting and retreating glaciers are becoming important freshwater reservoirs, and their value depends on their storage capacity and sedimentation-dependent lifespan. This study estimates the volumes and lifespans of >70,000 glacial lakes globally as of 2020, improving our understanding on the potential of these lakes and the sustainable use of these reservoirs.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Resistance noise in memristive devices is often described as a thermally activated process across simple energy barriers, but this can underestimate the role of entropy in a complex free energy landscape. Quantifying transition rates between discrete resistance states during resistance fluctuations in nanoscale GeTe shows that entropic contributions can strongly shape the free energy barriers.