Search

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

An analysis of 204 countries estimates that diabetes will cost the global economy $10.2 trillion between the years 2020 and 2050.

In single-particle cryo-EM, datasets often contain molecules that exist in a heterogeneous mix of states. Here, the authors compare different computational tools to study this heterogeneity and derive metrics to quantitatively compare their results.

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.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Known to augment host innate immunity, Zhou and Ahearn et al. shows that a SARS-CoV2 NSP15 mutant also increases viral recombination and reduces sub-genomic message. Results articulate a novel role for NSP15 in viral transcription and recombination.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

ADGRL4 is a cancer-implicated adhesion GPCR whose ability to couple to G proteins had been unclear. Here, authors show that ADGRL4 weakly engages Gq and determine its 3.1 Å active-state structure, revealing its mechanism of activation.

The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.

Pre-treatment dual immune checkpoint blockade in cervical cancer remains understudied. In this trial, the authors show that neoadjuvant immune checkpoint blockade enhances immune activation and correlates with improved response to subsequent chemoradiation in patients with cervical carcinoma.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Accurate projections of heating and cooling needs are vital for planning energy use and achieving the sustainable development goals. A global dataset now maps global heating and cooling degree days, finding future hotspots, rising cooling demand and early shifts in energy needs with major global impacts.

Data collected from zoos and aquariums worldwide show that hormonal contraception or permanent surgical sterilization in mammals increase life expectancy, with different mechanisms in males and females.

Core excitons are strongly localised excitonic states impacting x-ray absorption and resonant inelastic scattering (RIXS) spectra. Here, the authors demonstrate an application of free electron laser-driven ultrafast RIXS spectroscopy to study previously unclear aspects of core exciton-phonon interactions in graphite.

Methods for the systematic synthesis and evaluation of large numbers of transition metal complexes at a time are still limited. Here, the authors report a high-throughput method to create and test hundreds of metal complexes, revealing potent new metalloantibiotics and a highly active iridium catalyst.

In this study, the authors develop NTAC, Neuronal Type Assignment from Connectivity, using synaptic connectivity alone to identify cell types with high accuracy within minutes on a standard CPU.

Proton-exchange membrane water electrolysers rely on iridium to catalyse their anodic reaction, and while ruthenium is a less costly alternative due to its similar activity, it is not as stable. Now, a hierarchical machine-learning catalyst discovery workflow, termed mixed acceleration, is put forward to predict catalyst synthesis, activity and stability, and identify promising RuO_x-based water oxidation catalysts.

Reduced GC-related content in the influenza A virus genome may be a necessary condition for sustained mammalian transmission and should be included in risk assessment tools for pandemic influenza.

The authors report an enhancement of the superconducting onset temperature in nanometer-thin YBa₂Cu₃O₇-δ films grown on substrates with nanofaceted surfaces. They theoretically show that the enhancement is mainly driven by electronic nematicity and unidirectional charge density waves, and further suggest that the nanofacets themselves may promote these effects.

After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

Dielectric materials are crucial for advancing nanoelectronics, yet their miniaturization poses significant challenges. Here, the authors synthesize atomically thin gallium oxide on graphene, achieving a clean interface and robust electronic properties, paving the way for scalable integration of conducting and insulating components in nanoelectronics and offering a versatile method for oxide synthesis.

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.

Manipulating the chemical composition of proteins and peptides has been central to the development of polypeptide-based therapeutics and to help address fundamental biological questions. This Review describes how nature-inspired protein ligation strategies have been repurposed as chemical biology tools.

The microstructure of natural materials such as bone and wood makes them strong and tough. Chemists are also good at crystallizing fine particles, but a flexible adhesive is needed to bind them together. Daedalus thinks he has the answer.

PMTs are fungal O-mannosyltransferases embedded in the ER membrane. Here, structures of the Pmt4 homodimer reveal distinct features of this PMT family and uncover an additional cytosolic binding site for the Dol-P-Man substrate lipid.

NbN/AlN/NbN qubits prepared by atomic layer deposition allow for precise control of the tunnelling barrier and stable operation beyond the temperature limit of aluminium-based devices.

Vaccinations against the SARS-CoV-2 KP.2 variant were introduced for the 2024-25 season in the United States. Here, the authors investigate the effectiveness of these vaccines up to April 2025 through a target trial emulation study using electronic health record data.

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.

Systems of electron spins in nuclear-spin-rich hosts are gaining attention for quantum memory applications. Using spin ensemble studies, the authors propose transition metal ions in halide double perovskites as promising candidates, featuring long electron spin coherence and deterministic nuclear spin control.

Mutations in GJB2 cause DFNB1, the most common hereditary deafness. ATAC-seq identification of gene regulatory elements enables targeted GJB2 delivery to cochlear cells, preventing hearing loss in mouse models.

Green subsidies (carrots) are now becoming a more politically acceptable climate policy option compared with corrective regulations (sticks). However, researcher show that carrots without quick and appropriate sticks will not be sufficient to reach the deep decarbonization goal in the long run.

Chronic stress disrupts the brain vasculature and contributes to mood disorders, but mechanisms of resilience remain unclear. Here, the authors show that enriched environments increase astrocytic Fgf2 to prevent stress-induced vascular alterations and depressive behavior with relevance to human depression.

By carefully dispersing small amounts of Ir into the RuO₂ lattice, a Ru₆IrOₓ catalyst reduces Ir usage by 80% while still running stably for over 1,500 h at 2 A cm⁻² in both laboratory- and industrial-scale proton-exchange membrane water electrolysers.

Inhibition of AMPK activation under low glucose conditions in oligodendrocyte precursor cells is shown to be important for myelination during development and remyelination in neuronal disorders.

Using circularly polarized inelastic X-ray scattering, the authors map spin-wave (magnon) excitations in the altermagnet CrSb and detect a reversible chiral signal for the first time, establishing a practical method to probe altermagnetic magnons.

In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Here the authors implement a comprehensive timestamping across millions of pieces of biomedical evidence supporting target–disease associations in the Open Targets Platform and analyse trends in evidence supporting novel drug target discovery over the last two decades.

In a trial involving 45 clinics and 15,596 visits, the use of an AI-based screening tool applied to ECG for opportunistic detection of advanced chronic liver disease led to a significant increase in new diagnoses compared to the standard workflow.

Some surveys of intelligence have suggested that the mean IQ is rising; others, that it is decreasing alarmingly. The explanation seems to be that the educational level of the populations has changed.

Exercise has considerable health benefit, including modulation of the immune system. Here the authors compare the molecular make-up of peripheral blood immune cells at resting state and upon a single bout of two different aerobic exercise modes by proteomics and show that although both exercise modes trigger similar changes, the effect is more pronounced after high intensity interval training.

The microbial metabolite trimethylamine (TMA), the precursor of TMAO, which is associated with adverse cardiometabolic outcomes, is shown to have beneficial metabolic and anti-inflammatory effects in the host in the context of obesity.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.