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Exportin-1 (XPO-1) inhibitor selinexor has been reported as a therapeutic option in solid cancer. Here, the authors present a phase 1 clinical trial combining selinexor with chemotherapy by gemcitabine in patients with advanced sarcoma.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

It is generally acknowledged that pathological B-cell receptors drive chronic lymphocytic leukaemia (CLL) via continuous signalling emanating from BCR-BCR homotypic interactions, rather than external antigens. Here the authors show, by analysing the structure and function of three B-cell receptors from patients with stereotyped CLL subset 1 that homotypic interactions and consequential autonomous signalling is not universal and other mechanisms could play roles in leukemic proliferation of CLL cells.

JWST’s COSMOS-Web survey is used to create an ultra-high-detail dark matter map, revealing hidden filaments, clusters and distant structures. By tracing features out to z = 2, this map shows how dark and luminous matter build the cosmic web across cosmic time.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Chronic stress disrupts the brain vasculature and contributes to mood disorders, but mechanisms of resilience remain unclear. Here, the authors show that enriched environments increase astrocytic Fgf2 to prevent stress-induced vascular alterations and depressive behavior with relevance to human depression.

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.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Although noise is typically detrimental to quantum devices, it can serve as a resource for quantum thermal machines. Here, the authors demonstrate a device based on a superconducting quantum circuit that leverages noise to function as either a quantum heat engine or a refrigerator.

Analyzing data of the Mexican Biobank project, a new study finds regional differences in clinically relevant genetic frequencies and presents MexVar, a publicly accessible resource designed to support ancestry-informed genetic testing.

Patient-specific C. elegans model of Glycogen Storage Disease Type III shows significant glycogen accumulation. Through computational and drug screening approaches, CHK1 was identified as a potential modifier of disease-relevant phenotypes.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

Aneuploidy impacts differentiation and threatens the safety of stem cell therapies. Here, the authors show that mosaic aneuploidies are eliminated during RPE differentiation, except 1q gain, which is rescued by co-culture through paracrine signals.

CELSR1 is a core component of the tissue/planar cell polarity pathway. Here, the authors report a CELSR1-related disorder featuring brain malformations, neurodevelopmental delay and epilepsy, and use mice to explore the pathophysiological mechanisms.

Cryo-EM structures of yeast complex II in active and inhibitor-bound states reveal fungi-specific features governing enzyme stability and fungicide binding, paving the way for structure-guided design of improved inhibitors for agriculture and health.

Combination treatment with two antiviral drugs (oseltamivir and baloxavir) effectively limits clade 2.3.4.4b A(H5N1) influenza virus replication and disease severity in ferrets.

Growth differentiation factor 15, hemoglobin A1c, cystatin C, leptin and insulin levels were consistently and positively associated with measures of multimorbidity, both cross-sectional and longitudinal, in individuals aged 60 and over.

How proteins — sequences of amino acids — fold determines their function. We discuss efforts towards the establishment of metrics traceable to the International System of Units that link the sequence of a protein to its structure and function.

Fractal analysis of structural MRI captures the formation of brain shape in human newborns and outperforms other morphological measures in predicting infant age and genetic similarity, including the identification of twins from their brain data.

This study assessed the durability of immunity in humans after vaccination with an MVA-based MERS vaccine. The data show that antibodies and T cells persist for at least two years, with the antibodies capable of cross-neutralizing MERS-CoV variants.

Different agonists produce equilibria of at least four distinct active states of the G-protein-bound M2 muscarinic acetylcholine receptor, each with a different ability to activate G proteins.

Fermionic currents of opposing chirality can be spatially filtered without the need for a magnetic field using the quantum geometry of topological bands in single-crystal PdGa.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Using Mendelian randomization, no causal links were found between estradiol exposure and brain age gap, Alzheimer’s disease and depression in females. The pattern was consistent for estradiol levels in pre- and postmenopausal samples and males.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Profiling of microRNAs reveals their dysregulation in the Alzheimer’s disease brain. Further biochemical analysis shows their association with tau pathology and a potential role in modulating the progression of tau pathology.

This study applies a global food and land system modelling framework to quantify the impact of 23 food system measures on 15 outcome indicators related to public health, the environment, social inclusion and the economy—from today until 2050.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

The somitic mesoderm is seen as the main source of brown adipose tissue, although some depots are of partially unknown origin. Here, the authors show that Osr1 labels multipotent dorsal aorta progenitors at E9.5 that contribute to cartilage, muscle, and adipose tissues, revealing a non-somitic contribution to several brown adipose depots.

The impact of transcription on germline mutagenesis remains poorly understood. Here, the authors identify a mutational hotspot at transcription start sites in the human germline that is significantly enriched with early mosaic variants; they also analyse the molecular mechanisms that could cause it and explore its potential consequences for disease.

Interwoven magnetic and non-magnetic layers in TbTi₃Bi₄ overcome kagome frustration, producing coupled elliptical-spiral magnetic and spin-density-wave orders and a very large anomalous Hall effect driven by strong electron–magnetic field interactions.

PPARγ regulates glucose and lipid metabolism, yet safer PPARγ-targeted insulin sensitizers are needed to treat metabolic disorders. Here, Kuang-Ting et al. elucidate structure–function relationships of non-covalent inverse agonists that enhance receptor binding and improve insulin sensitivity, providing a framework for next-generation drug design.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Aortopathy poses a high risk of aortic dissection, particularly during pregnancy and the postpartum period. Here the authors report a retrospective case series of seven women with aortopathy who underwent PEARS, a surgical strategy to prevent aortic root dilatation, and a subsequent pregnancy.

The human CYFIP1 gene is linked to brain connectivity defects in neurodevelopmental disorders (NDDs). Here authors showed that reduced calcium uptake underlies CYFIP1-related axonal defects, potentially contributing to NDDs.