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In a case series of eight pediatric patients with systemic lupus erythematosus, dermatomyositis or systemic sclerosis, autologous anti-CD19 CAR T cell therapy was feasible, safe and effective in reducing disease activity.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

Da Pra, Boriati and colleagues show that physiological glucocorticoids suppress growth-factor-induced cardiomyocyte regeneration by inhibiting ERK signaling and propose glucocorticoid receptor antagonism as a strategy to enhance their protective and regenerative effects.

Glucose deprivation triggers the secretion of the cytokine LIF, which promotes angiogenesis and immune suppression in lung cancer models.

Kornfeld-Sylla et al reveal how alpha brainwaves are altered in children and adults with Fragile X Syndrome (FXS) and find parallel changes in alpha-like rhythms in juvenile and adult FXS model mice, showing their use for testing potential therapies.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

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.

Studying many-body quantum chaos on current quantum hardware is hindered by noise and limited scalability. Now it is shown that a superconducting processor, combined with error mitigation, can accurately simulate dual-unitary circuit dynamics.

In a double-blind, placebo-controlled phase 2 trial in patients with metastatic renal cell carcinoma treated with anti-PD-1 plus a VEGFR tyrosine kinase inhibitor, donor fecal microbial transplantation (FMT) from complete responders to immunotherapy did not significantly improve the primary endpoint of 12-month progression-free survival (PFS) but did significantly improve median PFS versus placebo FMT.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

The role of oxytocin in modulating astrocytes during stress behaviour is not fully understood. Here the authors show that in the amygdala, oxytocin modulates stress related behaviour by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium.

Arrays of nanowire loops consisting of two temperature-dependent superconducting switches and a variable kinetic inductor can be used to create a robust and scalable superconducting memory.

Rizzollo et al. show that BDH2 participates in iron distribution between cellular compartments, which sets the threshold for the ferroptosis vulnerability of the melanoma cell phenotypes, ultimately affecting their metastatic capacity

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

How neural responses to boundaries develop in the subiculum remains unknown. Here authors show that the receptive fields of Boundary Vector Cells (neurons signalling vector displacement to boundaries) are altered by environment geometry, with directional tunings aligning with square arena walls, including during development.

Smoldering multiple myeloma (SMM) may develop into life- threatening MM, with gut microbiota and Th17 possibly contributing to this progression via unknown mechanisms. Here the authors use a mouse SMM model, VkMYC mice, to show that treatments with butyrate or the commensal, Prevotella melaninogenica, suppress Th17 and cancer progression.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.

Supersolids combine superfluid and crystal order and their response to external driving remains unclear. Now it is shown that, in a dipolar supersolid, rotation induces synchronization of the crystal motion via vortex nucleation.

Chromatin structure is regulated by chemical modifications of histone proteins, but measuring these at single-cell resolution has been challenging. Here, the authors develop a mass spectrometry-based method to profile histone modifications in individual cells, revealing chromatin heterogeneity and differential co-regulation.

Platelets are known to have functions beyond those in thrombosis and haemostasis. Here the authors use multi-colour flow cytometry and proteomics to analyse platelet phenotypes in psoriatic disease and proteins that are potentially involved in the interaction of platelets with immune cells.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

Comprehensive large-scale studies of multi-national populations identified microbiome species consistently associated with favourable and unfavourable health markers, informing future studies of the human gut microbiome and its association with diet and cardiometabolic conditions.

Coagulation factor IX (FIX) contributes to hemostasis through both plasma activity and binding to extravascular collagen IV. Here, the authors show that collagen binding of albumin-fused hyperactive FIX can be engineered to tailor the pharmacokinetics, distribution, and functional properties in mice for tailored short- or long-term hemophilia B therapy.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.

The authors have previously reported split-GFP-based contact site sensors (SPLICS) to document endoplasmic reticulum/mitochondria contact sites. Here they extend this work and develop a range of improved SPLICS sensors to detect single and multiple organelle contact sites at different distances.

Malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division.

Haematopoietic stem cell (HSC) clonogenic activity, lineage output, lineage commitment and somatic mutation rates are influenced by the underlying disease, patient age, extent of genetic defect correction and hematopoietic stress imposed by the inherited disease, suggesting HSC adaptation.

Protein structure can be predicted from amino acid sequences with unprecedented accuracy, yet the prediction of protein–protein interactions remains a challenge. Here, authors present a sequence-based model that jointly encodes protein pairs, achieving state-of-the-art cross-species and virus-host PPI prediction and mutation effects analysis.

This study uses somatic mutations as a natural barcoding system to retrospectively and prospectively trace the fate of hematopoietic stem cells across all major blood cell lineages in healthy aged individuals. It reveals the existence of intrinsically fate-biased hematopoietic stem cells in native human hematopoiesis, validated by transplantation assays.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.

Asymmetric cell division often requires alignment of the mitotic spindle to cortical polarity cues. Here the authors show that cortical Wnt signaling induces formation of a complex between NuMA/dynein microtubule motors, LRP6 and β-catenin that promotes asymmetric division.

Mejía-Ramírez, Iáñez Picazo, Walter et al. explore how nuclear biomechanical changes limit the regenerative capacity of aged hematopoietic stem cells and show that targeting RhoA rejuvenates aged hematopoietic stem cells by reducing nuclear envelope tension and remodeling nuclear architecture.

Beneficial effects of fasting combined with endocrine therapy for oestrogen receptor-α-expressing breast cancers can be recapitulated using exogenous glucocorticoid receptor ligands instead of fasting to reduce harmful effects.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Emission of methane from ‘point sources’—small surface features or infrastructure components—is monitored with an airborne spectrometer, identifying possible targets for mitigation efforts.

Neural mechanisms underlying state-dependent flexible selection are not fully understood. Here authors show that NPY homologues in Drosophila larva differentially modulate reciprocally connected inhibitory neurons to bias non-feeding decisions, favoring escape-type actions (Head Cast), over protective-type actions (Hunch), in response to a mechanical cue.

Pretrained on SpatialCorpus-110M, a curated resource of vast and diverse transcriptomes of dissociated and spatially resolved cells from both human and mouse, Nicheformer advances toward building foundation models for spatial single-cell analysis.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.

Light can control neural activity but often requires genetic modification. Here, the authors present a graphene-based platform for non-genetic light controlled neuronal stimulation, enabling all-optical network analysis, stem cell derived neuron maturation, and closed-loop robotics.