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Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

The authors find that O-GalNAc transferase 2 (GALNT2) restricts viral infection, probably through the regulation of the proteolytic processing of viral glycoproteins via its O-linked glycosylation activity, impairing virus–cell fusion.

Lymphatics maintain lipid transport, immunity, and fluid balance. Kim J and Chaudhary S et al. reveal an AIBP-driven cholesterol efflux mechanism that regulates lymphangiogenesis via VEGF signaling.

HIV remission of more than 6 years was achieved in a patient with functional viral co-receptors after CCR5 wild-type/Δ32 allogeneic stem cell transplantation, providing evidence of other mechanisms that can be harnessed to attain long-term remission.

Cytosolic CHMP5 is known for its primary function in membrane remodelling. Here the authors report that nuclear CHMP5 promotes T cell acute lymphoblastic leukemia initiation and maintenance in part through regulating epigenetic and transcriptional events.

Extrachromosomal circular DNAs (ecDNAs) are prevalent in human cancers and are thought to drive tumor evolution and drug resistance by amplifying oncogenes. Here, authors develop ec3D to reconstruct three-dimensional ecDNA structures, revealing how their spatial organization rewires regulatory circuits.

PSC can be differentiated into blood cells in vitro. In this report, Sun and Motazedian et al describe a differentiation method that generates blood-forming endothelial cells that push newly emerging blood cells to become lymphocytes.

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.

Human embryonic stem cells are differentiated to cells similar to the embryonic aorta-gonad-mesonephros, which gives rise to hematopoietic stem cells.

Motazedian et al. examine human T-cell genesis in haematopoietic organoids and show that RAG1 marks multipotent T-cell progenitors that arise directly from the haemogenic endothelium.

R2 retrotransposons are natural RNA guided gene insertion systems. Here, Edmonds et al. characterize the structure and biochemistry of an avian R2 and engineer a compact, all-RNA system to integrate DNA in mammalian cells, aiding the development of future retrotransposon-based gene editors.

Human hematopoietic cells derived from pluripotent cells repopulate multiple blood lineages in mice.

Huang and colleagues report that TIM4–AMPK signaling induces downregulation of the mitochondrial HSP90 chaperone TRAP1 in tumor-associated macrophages, thereby enhancing their immunoinhibitory function and promoting immune evasion and tumorigenesis.

Adoro and colleagues report the involvement of the IRE1α–XBP1 signaling axis in protecting hematopoietic stem and progenitor cells from proteomic stress and as a safeguard against leukemic transformation.

Oxide memristors exhibit noise in excess of 2–4 orders of magnitude above the baseline at quantized conductance states. Here, the authors measure anomalous electrical noise at these states in tantalum oxide memristors and relate it to thermally-activated atomic fluctuations by numerical simulations.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

This study presents FolTAC-dual, a folate receptor-mediated platform for dual degradation of EGFR/HER2 and PD-L1/VISTA, offering a strategy to overcome drug resistance and enhance antitumor immunity for cancer treatment.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Using lipid nanoparticle delivery of mRNAs to the liver in aged mice, T cell function and declining immune cues can be restored.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

Andy Feinberg and colleagues show in a colon cancer model that most DNA methylation alterations occur in sequence regions distinct from promoters or canonical CpG islands, termed 'CpG island shores', and that this methylation is strongly related to gene expression and can discriminate tissue types regardless of species of origin.

As presented at the ESMO Congress 2025: Results of the phase 2/3 AGITG DYNAMIC-III trial show that de-escalated chemotherapy based on ctDNA-negative status in patients with stage III colon cancer did not meet non-inferiority for 3-year recurrence-free survival when compared to standard of care, although it enables better informed treatment decisions.

Urine can be used to easily analyse the health of patients. Here, the authors identify proteins in urinary extracellular vesicles that distinguish prostate cancer from benign lesions.

A human embryonic stem cell line expressing a fluorescent reporter of cardiac differentiation is described. The authors use this tool to optimize differentiation methods and to identify cell-surface markers in the cardiac lineage.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

Adipogenesis associated Mth938 Domain Containing gene (AAMDC) is frequently amplified in the IntClus2 subgroup of ER + breast cancer. Here, the authors show that AAMDC drives tumourigenesis through activating PI3K-AKT-mTOR pathway for metabolic reprogramming.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

Here, authors use NeuroPainting, a high-content imaging assay, to reveal cell-type-specific effects of 22q11.2 deletion in neural cells, linking adhesion gene dysregulation to mitochondrial and structural abnormalities, especially in astrocytes.

Mouse models show that respiratory infections from viruses such as influenza and SARS-CoV-2 can trigger metastasis of dormant breast cancer cells in the lungs, a finding supported by epidemiological data from two large human cohorts.

Keller and colleagues show that haemogenic and vascular endothelium represent distinct lineages and that haemogenic endothelium gives rise to multipotent haematopoietic progenitors through a NOTCH-dependent endothelial-to-haematopoietic transition.

The role of phosphorylated CTD interacting factor-1 (PCIF1) in neuropathic pain-anxiety comorbidity remains elusive. Here, authors identify the SERBP1–PCIF1 complex, which targets m6Am modification in glutamatergic neurons of the S1HL, as a potential therapeutic target.

A novel personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off may represent a viable alternative approach for the treatment of antimicrobial-resistant bacterial infections.