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In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.

Therapeutic gene editing in vivo is an ongoing challenge. Here, authors demonstrate Cas9 nickase guided DNA ligation as a nonviral method for installing permanent genomic corrections with favorable on target edit profiles in model animal cell types and adult mice.

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

Shroom3 genetic variants increase Shroom3 levels and promote kidney fibrosis but reduce proteinuria, complicating Shroom3 targeting for precision medicine. Here, the authors show increased fibrosis mediated by Shroom3–Rock signaling and blocking this interaction genetically or with new compounds reduces tubular Rock activation and fibrosis.

Engineered Escherichia coli strains expressing a colibactin antitoxin, ClbS, on the surface prevent the genotoxic effects of colibactin released by genotoxin-producing bacteria in the mouse gut.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

In this work, authors present their goal-directed subgroup identification (GD-SI) framework, reconciling biological heterogeneity with clinical actionability, and offering a scalable infrastructure for precision trial design and personalized sepsis management.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

The authors theoretically delineate the maximal increases in tree growth that can be expected from increases in plant intrinsic water-use efficiency, which increases with rising CO₂. They highlight environmental and physiological limits on growth in the context of experimental data.

A transverse Peierls transition can occur when transverse acoustic phonons couple with conducting p-orbital electrons. Here, the authors observe an incommensurate transverse Peierls transition and signatures of a chiral charge density wave in EuAl₄.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Research in the tropics is unevenly distributed across regions and biomes. Here, the authors find that moist broadleaf forests account for 73% of all tropical citations but cover 29% of the land area, while drier, climate-vulnerable areas with fewer trees remain under-sampled and under-cited.

A simple transport model infers a material’s electronic dimensionality from standard transport measurements, revealing temperature-, doping- and alloying-driven shifts between low-dimensional and 3D transport in SrTiO₃, Bi₂O₂Se and Pb_1-xSn_xTe.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

Diverse genomes of lytic phages are found in bacterial assemblies, challenging assumptions about the nature of the lytic lifestyle.

The authors previously pinpointed OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. Here, the authors identify increased IL-18Rα expression on CD8⁺ T cells, which acquire a reduced cytotoxic signature, correlates with severe respiratory viral infection of influenza A virus, RSV and COVID-19.

Laser-induced conversion electron Mössbauer spectroscopy, which detects electrons emitted by ²²⁹Th nuclei in a thin ThO₂ sample excited by vacuum ultraviolet light, is demonstrated, opening the possibility of a conversion-electron-based nuclear clock.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

A re-assessment of the global carbon budget shows the natural land sink is substantially smaller than previously estimated, indicating emerging impacts of climate change on the evolution of the carbon sinks.

Combining liquid crystals and nanocrystals functionalized with promesogenic ligands yields an interstitial colloidal solid solution exhibiting high thermal expansivity and reversible superlattice phase transitions driven by mesogen diffusion.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Barnett et al. disentangle the differential contribution of mitochondrial complex I- and complex III-derived ROS to astrocytic function, with CIII-derived ROS being a major driver of neuroinflammatory responses.

The HTLV-1 capsid (CA) domain of Gag was resolved to 3.4 Å resolution and reveals insights into immature lattice stabilization, the varying lattice curvatures and distances from the membrane, and the dispensable nature of inositol hexakisphosphate (IP6) for immature particle assembly.

Recently, two oxidative enzymes have been reported to degrade extremely recalcitrant plastics, PVC and PE. Here, the authors show that these encouraging previous results could not be reproduced, and provide possible reasons for why the data may have been misinterpreted.

The molecular mechanisms that regulate postnatal termination of neurogenesis remain poorly described. Here authors report Prdm16 deletion leads to the retention of radial glia in adulthood and prolonged postnatal neuroblast production.

Quantum lock-in detection (QLID) is crucial for extracting oscillating signals from noise, while quantum entanglement is vital to surpass the standard of quantum limit in precision measurement. Here, the authors experimentally realise entanglement-enhanced QLID using two trapped ions, achieving frequency measurement precision at the Heisenberg limit and demonstrating an improved inverse-quadratic temporal scaling.

Slippery covalently attached liquid surfaces are useful in many applications that require low-static friction to droplets. This review compares six prominent methods for preparing polydimethylsiloxane bound to silica surfaces and highlights pitfalls and time savers.

The Einstein Probe has discovered a fast X-ray transient, EP240414a, associated with a broad-lined type Ic supernova. Its unusually soft spectrum and weak jet add to the diversity of stellar deaths and suggest a previously unknown Wolf–Rayet star explosion mechanism.

Here the authors report NiGa₂O_4–x(OH)_y for light-driven CO₂ hydrogenation to methanol. The surface Lewis acid–base pairs and -OH groups act as conduits for H^- /H⁺ transport to active sites, enhancing photocatalytic methanol production.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Williams et al. report a growth arrest mechanism in residual cancer persister cells through targeted therapy-induced upregulation of type I interferon signalling, which is negatively regulated by apoptotic DNA endonuclease DFFB to allow tumour relapse.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

Goel et al. produce high-resolution three-dimensional genome structure mapping from mitosis to G1 phase to show unseen interactions between enhancers and promoters in prometaphase. Polymer modeling indicates the interactions are facilitated by chromosome compaction.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The properties of many high-temperature superconductors are governed by holes rather than electrons. Gauquelin et al. use atomic resolution electron energy loss spectroscopy to study the effect of oxygen doping on the valence of Cu ions and local electronic structure around the oxygen atoms in YBa₂Cu₃O_6+δ.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

A multi-institute, multi-platform initiative generates standard metrics and best practices for spatial transcriptomics analysis.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Single-layer graphene, owing to its impermeability, is a promising candidate to prevent transmembrane ion transport. Here, the authors report a covalent functionalization method that enables centimeter-sized graphene to function as a proton exchange membrane in a direct methanol fuel cell.

A long-lived photoinduced metastable state in a quasi-one-dimensional cuprate, Sr₁₄Cu₂₄O₄₁, is reported.