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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.

Li et al. report a spatially decoupled heavy atom antenna strategy by integrating alkyl bromides into a hybridized local and charge-transfer scaffold, originated from benzothiadiazole acceptors, to create an organic scintillator with a short radiative lifetime of 3.42 ns and spatial resolution around 50 lp mm^-1.

In vivo base editing of a causative mutation that leads to the neurodevelopmental disorder Snijders Blok–Campeau syndrome restores protein dosage and ameliorates molecular and behavioural deficits in a humanized mouse model of the condition.

The genetic basis underlying resistance to Sclerotinia stem rot (SSR) in oilseed rape remains elusive. Here, the authors identify BnaA07.MKK9 as a pivotal regulator of SSR resistance in oilseed rape by GWAS, providing new insights into plant defense mechanisms against necrotrophic pathogens.

Droplet impacts shape technologies from erosion to bioprinting. Here, authors show a scaling crossover in peak impact force on soft substrates, from inertial to Hertzian, unified by a similarity parameter. The proposed stress tomography provides a practical map to design impact-resistant processes.

Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

Macrocyclization typically proceeds via thioesterase mediation in type I polyketide synthases. Now, using genome mining and crystallographic analysis, an alternative mechanism for stereoselective macrocyclization in the akaeolide biosynthetic pathway is reported. The mechanism is proposed to proceed via an iminium-catalysed tandem Michael addition and Knoevenagel condensation, using nuclear transport factor 2-like enzymes.

Enzymes adapt by sampling new conformations while balancing destabilizing effects of mutations. Here, the authors reveal how TEM-1 β-lactamase acquires cefotaxime resistance through reshaping of dynamic conformational ensembles and localized stability networks, offering insight into the molecular framework of the activity-stability tradeoff.

This scoping review examines previous experience in performing silent evaluations of clinical AI applications, collecting evidence from 75 studies on implementation features and the sociotechnical context.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

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

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.

X-ray study of compressed water shows that superionic ice adopts mixed close-packed structures rather than a single phase - a far more complex behaviour than expected, mirroring solid ice’s rich phases and informing planetary interior models.

A rationally designed assay detects granzyme A activity by integrating peptide-based GzmA-targeted inhibitors and probes with chemiluminescent reporters to monitor inflammatory bowel disease.

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.

This research identifies two neural factors linked to externalizing and internalizing symptoms through a longitudinal imaging-genetic cohort. Distinct neural configurations and cognitive-behavioral relevance highlight the need for tailored therapeutic strategies addressing psychiatric comorbidity across developmental stages.

Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.

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.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

A bioresorbable microneedle sensor array provides continuous, wireless and multimodal monitoring of organ metabolism, oxygenation and electrophysiology for up to 7 days in postoperative kidney ischaemia and gut disorders.

The propagation of structured light in free space is bound to the existing solutions of Helmholtz equation. Here, authors propose a hydrodynamic formulation of optics to design and generate well-known beam families and introduce additional specialized modes. The formalism is experimentally validated through optical tweezers and free-space communications.

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 enzyme PCMT1 was found to install a C-terminal cyclic imide modification on proteins that marks them for degradation by CRBN, uncovering a conserved protein turnover pathway with implications in metabolism and neurological function.

Micromitophagy is found to occur in plant male germline cells, mediated by ATG5–HSP90.2 signalling, and is evolutionarily conserved in angiosperms. This mechanism underpins paternal mitochondrial elimination and supports the zygote-to-embryo transition.

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.

Signalosomes amplify cellular responses, but how they avoid uncontrolled activation is unclear. The authors use quantitative super-resolution imaging and mathematical modeling to reveal optimal RIP3:RIP1 ratios that ensure precise cell death signaling.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

The authors developed MOBILE, a compact photoacoustic imaging system for non-invasive hemodynamic monitoring in motion. It reveals how microcirculation adapt during exercise, offering a dynamic window into cardiovascular health.

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.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

Lattice strain impacts battery cathode performance and cycle life. Here, authors visualize and quantify strain in layered oxides through electron backscatter diffraction imaging, revealing heterogeneous, cycle-dependent distortions that slow Li transport and limit capacity, with irreversible layer bending driving capacity fade.

This study identifies regions and features of three stages of plateau evolution in the present-day Tibetan Plateau, based on structural features of intra-crustal low-velocity zones, depth of the crust-mantle boundary and surface topography.

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.

Age-related inflammation is a key mediator of the pathogenesis of osteoarthritis (OA), but the mechanism is not fully understood. Here, the authors show that IL-36 agonists are systemic inflammatory factors released from aged skin to promote senescence in joint cells and aggravate OA progression.

Zeng et al. analyzed cfDNA methylation and fragmentomic data from 1,294 patient plasma samples across 14 major cancer types to present a comprehensive landscape of pancancer and cancer-specific cell-free DNA methylation and fragmentomic features.

Metabolite signatures were identified for subtypes of dietary carbohydrate, including added sugar, whole grain and refined grain, and showed different associations with type 2 diabetes, providing an objective measure of dietary risk.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

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.

Metabolic syndrome (MS) is associated with enhanced risk to develop endometrial cancer (EC). Here, the authors show that oleic acid, increased in MS, promotes endometrial cancer by supporting the stability of the rate-limiting enzyme in polyamine metabolism ODC1 and polyamine accumulation.

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.

Authors report drug repurposing screens against O-GlcNAc cycling enzymes, finding kinase inhibitors that act as splicing modulators to disrupt O-GlcNAc homeostasis and downregulate OGT and OGA. These findings reveal splicing modulator chemotypes and approaches to disrupt O-GlcNAc homeostasis.

Natural hydrogen is generated through chemical and radioactive processes in the Earth’s crust, and could be an important future clean chemical feedstock and energy resource. This Review examines the processes of geological hydrogen generation, migration, accumulation and preservation that enable the development of exploitable reserves.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Per- and polyfluoroalkyl substances (PFAS) have substantial environmental and health hazards, but their persistence and stability challenge remediation efforts. Now, a lithium-metal-mediated electroreduction strategy has been developed to effectively degrade PFAS with a high defluorination efficiency across different functional end groups while allowing for upcycling of the released fluoride.