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The mediobasal hypothalamus plays a central role in integrating nutritional and sex-related signals to regulate energy homeostasis. Here, through snRNA-seq of the mediobasal hypothalamus in female and male mice across nutritional states, authors show that Agrp neurons are nutrition-sensitive, DA neurons exhibit transcriptional differences in a sex-dependent manner, and KNDy neurons are responsive to both sex and nutrition.

The paper reports a scalable, chemical-free plasma process that converts methane and water into high-purity, single-layer graphene oxide while co-producing hydrogen, cutting greenhouse emissions, and lowering cost compared with conventional methods.

Borneol has repelled mosquitoes for millennia, but how it worked was unknown. Here, the authors show the sensory pathway mosquitoes use to detect and avoid this ancient plant compound, opening the door to improved natural repellents.

Here the authors identify nicotine-derived inhibitors of the SARS-CoV−2 main protease that outperform Paxlovid in cells and mice, remain effective against resistant variants, and show broad activity against multiple human coronaviruses.

Spatial CRISPR screens probe the functional impact of mutations within intact tissues. Here, authors present Spatial Perturb-Seq, a technology that localizes CRISPR perturbations and cell identities in situ, uncovers communication between cells, and shows how genes act beyond their cellular borders.

Here, the authors map malignant and non-malignant cellular states in human glioma using integrated single-cell and spatial transcriptomics, revealing spatially organized tumor-microenvironment interactions and distinct oligodendrocyte-associated programs linked to disease progression.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

Kv7.4 channels regulate auditory function. Here, authors use electrophysiological, optical and computational methods to investigate the structural changes that drive Kv7.4-channel opening, and how these are impaired by a deafness-causing mutation

Dai and colleagues implicate defective dendritic cell migration in impaired vaccine responses in aged mice. Oral delivery of yeast-derived nanoparticles promotes migration of dendritic cells from the gut to lymph nodes and restores vaccine efficacy in aged mice.

Long-term patterns of physical activity and the importance of consistent adherence to the recommended level remain poorly understood. Here, the authors show that maintaining physical activity over the long term offers added benefits beyond activity volume alone for chronic disease prevention.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.

Combining metabolic theory with global datasets, Li et al. show that root water content is a stronger predictor of root growth traits than the widely considered root nitrogen, better reflecting fast acquisition strategies and leaf–root alignment.

Here the authors systematically benchmark 13 polygenic score (PGS) methods in UK Biobank European and African populations, revealing factors that affect prediction accuracy. They also introduce an automated platform for standardized and reproducible PGS computation.

The depiction of crop exposure to heat stress is fundamental for reliably quantifying extreme-heat-induced yield loss and crop failure. Using more than 130,000 subnational yield records, this study estimated spatially explicit extreme degree day thresholds for maize and soybean across major Northern Hemisphere breadbaskets, revealing strong geographic heterogeneity.

In this study, the authors designed potent Enterovirus D68 capsid inhibitors that block viral binding and show that the lead compounds reduce virus levels, prevent paralysis and improve survival in EV-D68-challenged mice, even when treatment starts days after infection.

Biogenic–anthropogenic interactions increase the formation and prevalence of secondary organic aerosol coatings on urban black carbon in Nanjing, China. These coatings amplify radiative effects, according to a model–data analysis for 2023.

MASH is driven by the secreted GPNMB ectodomain, which binds hepatocyte RYK to activate ERK1/2 and promote lipid uptake and lipogenic programs; blocking the GPNMB–RYK axis prevented and treated MASH in preclinical models.

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.

Biocatalysis of the chemotherapy drug, doxorubicin, relies on the cytochrome P450 DoxA, which is inefficient. Here, the authors ameliorated the biosynthetic limitations by identifying DoxA redox partners and DnrV, which prevents product inhibition, helping improve microbial production.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Wang et al. analyzed data from the Detroit Neighborhood Health Study to explore links between social adversity, post-traumatic stress and epigenetic regulation through blood-derived micro-RNA profiles.

Using a random regression model, the study shows there are varying genetic profiles that act on BMI from infancy to adolescence. Change in BMI across childhood is genetically correlated with several adult cardiometabolic traits.

Transesterification reactions are essential in organic chemistry, however, performing these reactions in aqueous media is challenging due to the competing hydrolysis reaction. Here, the authors report a mutant of alcohol oxidase from Phanerochaete chrysosporium (PcAOx-VPN) that exhibits no hydrolytic activity, enabling transesterification reactions in water.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

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 APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

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.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Expression of agouti signalling protein in neurons in the medial preoptic area is increased by group housing and negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant mice.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

A human spinal cord organoid model can replicate two different types of spinal cord injury and can be used as an in vitro system to evaluate therapeutics and inflammatory reactions to treatments.

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.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Cobalt-based catalysts are regarded as a potentially cheaper alternative to platinum and chromium systems for the non-oxidative dehydrogenation of propane, although they often feature lower performance. Now mixed-valence Co^0/IIO_x clusters supported on silicalite-1 are identified as a competitive system for this reaction.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.

PhytoBabel is an AI model designed to capture the semantic similarity of cis-regulatory sequences across phylogenetically distant plant species, thereby establishing an approach for cross-species knowledge transfer and gene function prediction.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

O’Shea and colleagues establish that optimisation of charge and stability is sufficient to enable any single-chain variable fragment intrabody to function within the cell. The authors use AI-led inverse folding to optimise intrabody characteristics, and they present hundreds of intrabody sequences targeting sixty cytoplasmic proteins.

The CATS Net framework models how abstract concepts emerge from sensory experience. Aligning with human brain activity and enabling knowledge transfer, it provides a unified framework for understanding conceptual intelligence in both humans and AI.

A 3D soft electronic mesh allows high-resolution electrical recording and stimulation across the full surface of neural organoids, enabling long-term studies, drug testing and optogenetic control without compromising their viability owing to its porous design.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

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.

DeepRare—a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating specialized tools and up-to-date knowledge sources—has the potential to reduce healthcare disparities in rare disease diagnosis.

This study uncovers genetic links between plant roots and their microbiome in Brassica napus, identifying microbe-associated loci and a beneficial bacterium, Sphingopyxis, that promotes nitrogen uptake.

While neoadjuvant chemotherapy can improve outcomes in patients with esophageal squamous carcinoma, resistance often develops. Here, the authors identify elevated INCENP and CDCA8 via YTHDF3 mediated translation as markers of poor response to neoadjuvant chemotherapy in esophageal squamous carcinoma.