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CLPP-deficiency-driven mitochondrial dysfunction in brown adipose tissue leads to the accumulation of d-2-hydroxyglutarate, in turn promoting lipid-droplet enlargement by altering gene expression and epigenetically regulating nuclear stiffness.

Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

Untargeted metabolomics demonstrate that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched, and inosine is identified as a metabolite released during apoptosis regulating thermogenic fat and counteracting obesity.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

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.

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.

Proxy records from Lake Baikal show that rapid cooling coincided with Northern Hemisphere ice sheet expansion 2.7 million years ago, a change accompanied by a transition to open steppe ecosystems.

Reverte-Salisa et al. show that, in preadipocytes, EPAC1 enhances brown adipose tissue growth and increases the function of thermogenic fat in obesogenic conditions. Activation of EPAC1 induces human brown adipocyte proliferation and differentiation.

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.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.

At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

The enzyme soluble guanylyl cyclase (sGC) regulates differentiation of brown fat. Here, Hoffman et al.show that a small molecule sGC stimulator increases brown fat activity and browning of white fat, thereby inducing energy expenditure, weight loss and partial protection from diet-induced obesity in mice.

A martensitic alloy with a tensile strength exceeding 3 GPa and a fracture elongation of 5.13% is developed. These mechanical properties arise from interface complexes interacting with dense dislocation networks, which is a mechanism shown to be applicable to other compositions.

Brown adipose tissue (BAT) produces heat by burning lipid triglycerides. Here, Berbée et al. show that pharmacological BAT activation protects hyperlipidemic mice from atherosclerosis, provided mice retain the metabolic capacity to clear cholesterol-enriched lipoprotein remnants by the liver.

Optomechanical crystals are promising building blocks for quantum networks but suffer from thermal mechanical noise. Here the authors demonstrate on-demand conversion of single phonons into high-purity telecom photons with low thermal noise and MHz-scale narrow bandwidth using a quasi-2D optomechanical system.

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.

Brown and beige adipose tissues contribute to organismal energy expenditure by generating heat. Here, Klepac et al. survey G protein-coupled receptors in brown fat and show that G_q-coupled receptors inhibit expression of thermogenic proteins in mice and in human adipocytes.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

Brown fat can dissipate energy as heat and has an important role in energy homoeostasis of rodents and possibly humans. Chenet al. show that microRNA 155 regulates the differentiation of brown adipocytes as well as the 'browning' of white fat cells in mice.

Nrf1-mediated proteosome activity in brown fat is required for the normal thermogenic behavior of this tissue in mice.

Chlorpyrifos is a widely-used pesticide and a common residue on vegetables and fruits. Here the authors show that at non-neurotoxic doses, chlorpyrifos reduces energy expenditure, by inhibiting diet induced thermogenesis, and promotes obesity and insulin resistance.

Brown adipose tissue (BAT) has high thermogenic potential and is considered a promising target to counteract obesity. Here de Jong et al. demonstrate that human BAT is more similar to classical brown than to beige adipose tissue from mice kept at thermoneutrality and challenged with a high-fat diet.

Single-cell transcriptomic analysis of progenitor cells from human adipose depots reveals an adipogenic and a structural branch of cells, the latter named SWAT cells and shown to display a multipotent phenotype.

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.

In this study, the authors develop a flavivirus vaccine strategy by introducing mutations into envelope glycoproteins resulting in structural changes that conceal the ADE-prone fusion loop epitope. They show that the Zika virus-specific construct protects mice against viral challenge and prevents ADE by Dengue virus.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Ginhoux, Dutertre and colleagues provide a comprehensive analysis of dendritic cell subsets and states across human tumoral and juxtatumoral tissues.

Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo, and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

Hanbury Brown and Twiss measurements on speckle patterns propagating along curved surfaces improve understanding of spatial coherence.

Haines et al. developed an MEK–RAF molecular glue called IK-595 that blocks MAPK pathway activation in RAS-mutant and BRAF-mutant cancer cells. IK-595 exhibited high tolerability and strong antitumor effects in preclinical models across cancer types.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

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.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

Macrophages serve important functions in defense and tissue homeostasis. Jung and colleagues demonstrate that a resident population of macrophages controls the innervation of brown adipose tissue and thereby regulates energy use.

The authors report the synthesis of (La_0.9Y_0.1)H₁₀ superhydrides and their characterization using synchrotron-based, spatially resolved x-ray diffraction and electrical transport imaging. They reveal μm-scale structural inhomogeneity with coexisting cubic and hexagonal clathrate phases exhibiting distinct superconducting transition temperatures.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Fusion genes involving KMT2A rearrangements are frequent oncogenic drivers of acute myeloid leukaemia (KMT2A-r AML) but the cell of origin remains unclear. Here, using preclinical models of EVI1 positive KMT2A-r AML the authors investigate the cell of origin and find that the presence of exogenous factors influences AML initiation and the resulting phenotype.

Structural designs based on the geometric arrangement of their building blocks have been utilized to develop advanced mechanical metamaterials. Here, the authors use the DNA origami method to realize a nanoscale metastructure exhibiting mechanical frustration, the mechanical counterpart of the well-known magnetic frustration, and show that this DNA metastructure can be precisely controlled to adopt either frustrated or non-frustrated mechanical states.

The data fusion method presented here integrates multi-omics datasets for gene prioritisation, biomarker discovery, and pathway enrichment analysis by finding genes and proteins with significant and directionally consistent changes across the data modalities.

Elevated triglyceride levels often occur in obesity and can contribute to cardiovascular disease. Brown adipose tissue (BAT) is known to burn fat, and now Joerg Heeren and his colleagues show that BAT actively takes up triglycerides in cold conditions, suggesting a possible therapy to lower triglyceride levels in states of obesity.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Hund’s exchange interaction energy in two-dimensional materials is challenging to extract from experiments. Now, this is achieved in rhombohedral graphene, which allows an estimate of the interactions that drive the variety of correlated states in this material.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

Zierer et al. engineered cassava to express a modified potassium channel that enhances sugar flow, improving the yield and drought resilience. This strategy offers a route to increase cassava productivity in tropical regions.

Flicker noise limits the performance of electronics. Here, the authors demonstrate in nanowires of charge-density wave materials (TaSe₄)₂I and NbS₃ that low-frequency electronic noise is suppressed below the limit of thermalized charge carriers in passive resistors.