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Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

Free fatty acids drive uncoupled respiration in white adipocytes, mediated in complex with ATP/ADP carriers, to modulate thermogenesis and cold tolerance in obese thermoneutral-adapted mice.

Mouse models show that lymphoedema caused by impaired lymphatic drainage is ameliorated by removal of cholesterol deposits, which promotes the regeneration of lymphatic vessels.

Using phylogenetic comparative methods across 237 species from disparate phyla, the authors show that species with fast-paced ecologies have higher temporal resolution of perception.

Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

Succinate metabolism is reported to be involved in acute myeloid leukemia (AML) tumorigenesis. Here, the authors demonstrate that succinate receptor 1 (Sucnr1) restricts hematopoiesis via regulation of S100A9, counterbalancing the Sucnr1-independent tumorigenic effect of succinate in AML.

Although antiretroviral therapies (ART) have expanded the life expectancy of patients with HIV, they are not curative due to the presence of latently infected cells. Here, the authors present IMC-M113V, a bispecific soluble TCR targeting the HIV peptide Gag_77-85 complexed to HLA-A*02:01 as an approach for targeting HIV reservoirs and test safety, tolerability and pharmacodynamics in a first-in-human clinical trial on 12 HLA-A*02:01-positive male individuals on ART.

Combining metabolic theory with global datasets, Li et al. show that root water content is a stronger predictor of root growth traits than the widely considered root nitrogen, better reflecting fast acquisition strategies and leaf–root alignment.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

Urbanization often leaves cities with fewer iconic species, and not just of animals. This study focusing on urban trees finds that urban trees have homogenized over large geographic differences but diversified over short ones.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Schizophrenia is a complex brain disorder with its underlying protein changes generally not well understood. Here, authors show widespread alterations in the prefrontal cortex, marked by reduced energy production and disrupted synaptic function.

A genetic study in over 300,000 males reveals that Y chromosome loss affects type 2 diabetes risk differently in East Asians and Europeans. Multi-omics data suggest that this may be due to impaired glucose metabolism in Y-deficient pancreatic β cells.

Biological system for stable object manipulation is facilitated by a unified tactile memory system. Here, GenForce enables transferable force sensing across diverse tactile sensors using a unified representation, enhancing robot manipulation through cross-sensor transfer and multi-sensor coordination.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

In this work, researchers build a scalable photonic Chern insulator by twisting a fibre during fabrication, breaking an effective time-reversal symmetry and inducing a pseudo-magnetic field. The team reveals a ‘Goldilocks’ regime that guarantees topological protection against fabrication-induced disorder of any symmetry class in the fibre cross-section.

Using plasma proteome profiles from over 53,000 UK Biobank participants, Zhang et al. examined proteins associated with suicidal behavior and investigated pathways that could explain the association

Preclinical studies indicate a synergistic effect of radiotherapy treatment (RT) and Immune checkpoint inhibitors (ICI) on tumor growth and metastasis. However, little is known about the immunomodulatory performance of different radioisotopes on the tumor microenvironment. Here, the authors employ alpha- versus beta-particle emitting radiopharmaceuticals in combination with dual ICI therapy and dissect mechanisms of in vivo immunomodulation and timing of ICI administration relative to RT, by comparing responses in immunogenic and non-immunogenic preclinical mouse models.

Here, in a cross-sectional study of 209 individuals living in communities with contrasting Schistosoma mansoni endemicity in Uganda, the authors identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

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.

Aerial surveys over the Permian Basin found 500+ major methane leaks, many recurring. A few sites leaked continuously and offer quick mitigation wins. These super-emitters may produce ~50% of regional emissions, underscoring the need for frequent monitoring.

This multidisciplinary response to investigate the large outbreak of unknown febrile illness in the Panzi Health Zone in the Democratic Republic of the Congo in late 2024 suggests that the outbreak was largely associated with malarial cases and concurrent viral respiratory infections.

Taniuchi and colleagues show that differential phosphorylation of the terminal Y residue in Runx proteins connect MHC restriction with the helper versus cytotoxic T cell lineage choice.

Huang, Rigau and colleagues observe major changes in how DNA is organized in early germ cells before they start developing into sperm or eggs. These results show that germline removes structural ‘memory’ of DNA folding to start fresh for the next generation.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Survival of reef-building oysters peaks at specific combinations of fractal dimension and height that reduce predation, showing how optimal three-dimensional habitat geometry can guide more effective ecosystem restoration.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

The bacterial genus Aeromonas includes emerging human pathogens, often misidentified as Vibrio cholerae. Here, the authors analyse genomic sequences of over 1,800 Aeromonas isolates, showing that clinical and environmental strains do not display clear differences in drug resistance or disease-causing potential.

Using interviews, this paper establishes that experts agree government intervention is critical in enabling climate-resilient housing, given the transformative potential of regulatory reform, finance, and information services.

The use of antimicrobial agents can exacerbate the proliferation of antimicrobial resistance genes, which can put public health at risk; evaluating this risk requires proper monitoring. An extensive investigation of Australian wastewater reveals a distinct correlation between the type of antimicrobial used and the socioeconomic status of the population.

Pico-C, a low-input Micro-C approach, reveals that dynamic three-dimensional genome folding precedes zygotic genome activation in Drosophila.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

Icosahedral viruses package their genomes into a proteinaceous capsid to near crystalline density. Here, the authors report cryo-EM-based insights into the post-packaging genome positioning, virion assembly and maturation mechanisms in the tailed bacteriophage T4.

Using two newly developed immunoassays tested in three clinical cohorts, this study highlights CSF DOPA decarboxylase as a promising biomarker for differentiating dementia with Lewy bodies and Parkinson’s disease from Alzheimer’s disease and controls.

BiG-SCAPE and BiG-SLiCE are computational tools that enable exploring the diversity of metabolic gene clusters across microbial genomes. Here, the authors present major updates to these tools, providing essential infrastructure for studying the diversity of microbial metabolism.

Authors study links between amyloid secondary nucleation and growth defects, demonstrating these sites on Aβ40/Aβ42 fibrils are rare compared to the number of protein molecules. Re-analysis of published data suggests that defects may also drive secondary nucleation generally.

In this analysis of biomolecular and archaeological data from a ninth-century BCE mass grave in the Carpathian Basin, Fibiger et al. find evidence for the targeted killing of mostly unrelated women and children, challenging views of prehistoric violence.

A human spinal cord organoid model can replicate two different types of spinal cord injury and can be used as an in vitro system to evaluate therapeutics and inflammatory reactions to treatments.

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.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Non-additive effect and trait-trait interactions are often overlooked in current genomic prediction approaches. Here, the authors extend quadratic phenotypic selection index to the genomic domain to enable phenotype-free, rapid-cycle multi-trait selection while capturing genome-wide nonlinear relationships.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

This study reports a post-assembly, reversible crosslinking strategy that enhances lipid nanoparticle (LNP)-mediated mRNA delivery while preserving efficient intracellular release. The resulting crosslinked LNPs enable improved endosomal escape, sustained in vivo expression and robust immune and antitumor responses across multiple clinically relevant LNP platforms.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

Birds are iconic and valued users of urban parks. An assessment of 935 parks across 186 US cities shows that a range of park features across multiple parks are needed to broadly support avian diversity and that the regional and seasonal effects of tree canopy cover are especially important.