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Negative regulation of the cGAS-STING pathway is crucial to limit damaging inflammation. Here, by combining in vitro experiments and myeloid cell-specific conditional knockout mice, the authors identify the autophagy receptor TAX1BP1 as a negative regulator of STING by targeting it for degradation through Golgiphagy and ESCRT-mediated microautophagy.

Massively parallel reporter assays across five cell types identify thousands of causal, noncoding regulatory variants among 220,000 loci, revealing diverse regulatory mechanisms shaping complex traits and disease.

Taxanes, such as docetaxel or cabazitaxel, are one of the few chemotherapy options for metastatic castration-resistant prostate cancer (mCRPC). Here, the authors discover that FOXJ1 modulation of microtubule dynamics regulates resistance to docetaxel in mCRPC.

Gestational exposure of mice to the obesogen tributyltin alters 3-D chromatin interactions in primordial germ cells leading to stable reduction of hepatic Ide expression and predisposing male descendants to insulin dysregulation and obesity.

Neural mechanisms underlying high visual acuity are not fully understood. Here the authors show that high resolution visual information is transmitted from the retina to the brain by neurons in the parvocellular geniculate pathway in macaques, where signals are now shown to most often originate from single cone photoreceptors, establishing the neural mechanism that limits resolution acuity prior to cortical processing.

The identification and optimization of bifunctional small-molecule protein degraders remain labor-intensive processes largely restricted to proteins with well-defined ligandable pockets. Here, the authors present a polymer-based strategy, HYbrid DegRAding Copolymer (HYDRAC): modular copolymers that densely display target-binding peptides in conjunction with peptide-based or small molecule-derived degrons in a multivalent fashion, enabling selective degradation of disease-relevant proteins.

Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

Cell division in many Gram-positive bacteria involves the synthesis of a peptidoglycan septum that is then hydrolyzed to facilitate cell separation. Here the authors show that, after septum formation, the cell wall at the division site is remodelled by transpeptidation as new poles form during daughter cell separation in Bacillus subtilis.

Chromosome folding in early zebrafish development starts with formation of fountains. These patterns, also prominent in other systems, form at active enhancers, depend on transcription factors, and reflect preferential loading of loop extruding cohesin at enhancers.

Ribosomes drive protein synthesis, but their dynamics are hard to visualize. Here, authors introduce RiboBright, a fluorescent probe that illuminates ribosomes in live and fixed cells, revealing cell-type-specific content, organization, and movement.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

This study uncovers hidden atomic order in high-entropy ceramics and shows it can be engineered to dramatically boost resistance to radiation damage, opening a new pathway for design of ceramics for extreme environments.

Here researchers reveal a microexon in the Ank3 gene encoding Ankyrin G allows cortical interneurons to fine-tune calcium signaling and firing, revealing the contribution of alternative splicing to the functional diversity among different types of neurons.

The severity of climate change impacts calls for low-carbon thermal management solutions. This work presents a chameleon-inspired electronic skin for adaptive electrochromic thermal regulation with minimal energy input and scalability potential.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.

Attention fluctuates over time and across contexts—how is this reflected in the brain? Fitting a dynamical systems model to fMRI data, Song and colleagues show that the geometry of neural dynamics along the attractor landscape reflects changes in attention.

Here, the authors propose the Antarctic Ecosystem Value Index, an Earth systems model-based measure of marine ecological value. The index identifies potential present and future high-value locations, which often fall within coastal polynyas.

Expression quantitative trait loci (eQTL) analysis in patients with inflammatory bowel disease identify potential target genes for IBD GWAS loci not readily detected in individuals without disease highlighting the importance disease-focused studies.

Top-down projections from the orbitofrontal cortex carry predictive signals that grow with sound experience and suppress the auditory cortex via inhibitory circuits, revealing a predictive mechanism for sensory habituation.

Here, the authors show that myoferlin is a crucial host factor that helps move viral genetic cargo to the cell surface, boosting influenza, RSV and Sendai virus spread, highlighting a common weak spot for future antivirals.

Researchers report a solid that is amorphous in two dimensions but crystalline in the third, made of stacked disordered atomic layers. This shows that crystalline and amorphous order can coexist within a single material depending on direction.

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.

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.

Previous studies of Teneurins identified an uncharacterized family of Teneurin-like proteins in bacteria. Here, the authors show these proteins are widespread across both Gram groups but limited to certain species, where they form barrel-like structures that encapsulate a toxin and are co-expressed with potent immunity genes.

Using recent TMTH-sulfoximine (THS)-based biorthogonal chemistry in live cells, Smits et al. identify micro- and nanodomains in cell-cell and cell-matrix contacts of heterogenous glycocalyx density in invading melanoma cells.

Here they show that FOXF2 is required for pericyte maturation and function during postnatal alveolar morphogenesis. FOXF2 is required in pericytes to induce angiogenesis after neonatal hyperoxic injury, revealing a link between pericyte-endothelial crosstalk and bronchopulmonary dysplasia pathogenesis.

This trial found spinal cord stimulation was well tolerated in people with gait-impaired Parkinson’s disease. It suggests that longer use improved lower-body motor symptoms while reducing thalamic hypermetabolism and cholinergic overactivity.

Surface plasmon-mediated steady-state and on-demand electronic spin modulation effectively activates light-driven plasmonic catalysis, facilitating polarization reactant activation and preferential reaction pathway modulation.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Amundsen Sea records show warm Circumpolar Deep Water drove major West Antarctic Ice Sheet retreat from 18,000–10,000 years ago. Subsequent cooling stabilized the grounding line, indicating ocean heat—not atmospheric warming—controlled long-term WAIS change.

Zhai et al. report newly designed self-assembled molecules exhibiting strong and ordered anchoring on the perovskite surface to reduce defects and modulate the dipole-induced energy-level, enabling certified efficiencies of 26.23% in a normal device structure, which are also applicable to inverted perovskite solar cells.

Biocatalysis of the chemotherapy drug, doxorubicin, relies on the cytochrome P450 DoxA, which is inefficient. Here, the authors ameliorated the biosynthetic limitations by identifying DoxA redox partners and DnrV, which prevents product inhibition, helping improve microbial production.

The physiology and behavioral function of proprioceptors that detect joint limits are not fully understood. In this study, the authors used calcium imaging, optogenetics, behavioral genetics, and the connectome to demonstrate that hair plate proprioceptors on the fly leg detect joint limits and engage circuits to drive the leg away from those limits.

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.

It is shown that an a.c. field exponentially extends the lifetime of a prethermal time crystal realized with nuclear spins in diamond, enabling a narrowband detection of magnetic fields.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

The APOE-ε4/ε4 genotype is the strongest genetic risk factor for sporadic Alzheimer’s disease. Here, Brutman et al. identify a deletion common in people of African ancestry that reduces the relative risk conferred by the APOE-ε4/ε4 genotype.

Many viral vaccine antigen candidates are transmembrane glycoproteins, and their development requires methods which allow their biophysical characterization. Here authors present an optimized nanodisc assembly platform which provides reproducible, scalable, and accurate replication of the vaccine candidates for detailed analysis.

While the benefits of crop diversity are known, doubts remain as to whether replacing cereals in rotations reduces nutrient production. A comparison of 16 long-term field experiments across Europe shows no trade-off between functionally rich rotations and food productivity.

Robust protein synthesis by the ribosome is required for rapid cancer growth. Here authors present interdictors, small molecule inhibitors of protein synthesis with context-dependent activity that inhibit MYC-driven cancer cell growth in a mouse model.

Lazarevic et al. reveal a shared loss of a TBX5-dependent atrial gene network in cardiomyocytes and a disease-specific network gain in activated fibroblasts across atrial fibrillation and heart failure models.

Early-life exposure to allergens triggers a distinct local mode of dendritic cell activation in neonatal skin without requiring migration to lymph nodes, which shapes responses to allergens in later life.

Skin-targeted siRNA therapies require optimized delivery to achieve therapeutic efficacy. Here, authors show that increasing conjugate hydrophobicity enhances siRNA skin retention and gene silencing in porcine and human models while limiting systemic tissue exposure.

Using a random regression model, the study shows there are varying genetic profiles that act on BMI from infancy to adolescence. Change in BMI across childhood is genetically correlated with several adult cardiometabolic traits.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

Anderson et al. demonstrate that the glucokinase activator AZD1656 reduces inflammation and reverses cardiac dysfunction and metabolic remodeling in mice with diabetic cardiomyopathy.

Multiple myeloma involves alterations to T cell function, but mechanisms underlying disease evolution remain unclear. Here the authors find that, unlike solid cancers, multiple myeloma lacks exhausted T cells and is instead characterized by antigen-driven terminal memory T cell differentiation, which may be driven by tumour-intrinsic features including tumour burden and antigen-presentation gene expression.

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.

This study quantifies the environmental impact associated with photovoltaics manufacturing and demonstrates significant CO₂ emissions savings, depending on solar cell technology and the composition of the electricity mix in the region of manufacture.