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Lv et al. discover that homologous disordered regions of proteins linked to ALS/FTD and Parkinson’s, CHCHD10 and CHCHD2, form amyloid fibrils in vitro and that the structures of these fibrils are consistent with potential roles for them in disease.

LARGE1 glycosyltransferase synthesizes matriglycan (xylose-glucuronate)_n on dystroglycan, and short matriglycan can cause neuromuscular disorders. Authors show that LARGE1 processively polymerizes matriglycan of defined length on prodystroglycan.

2D semiconductors hold promise for solution-processed circuits requiring low-cost components and manufacturing scalability. Here, the authors investigate the criteria for the electrochemical exfoliation of high aspect-ratio nanosheets from 28 different layered materials, identifying the most promising candidates and key bottlenecks for solution-processed complementary electronics and functional circuits.

Grid cells do not maintain a stable pattern during a self-motion-based task, but track animal movement in multiple local reference frames and reanchor to task-relevant objects, thus estimating local rather than global position.

Limited diagnostic capacity for asymptomatic individuals hinders malaria elimination efforts in Africa. Here, the authors present a near point-of-care method based on colorimetric LAMP detection that outperforms expert microscopy and commercial rapid diagnostic tests for Plasmodium detection in asymptomatic and submicroscopic individuals.

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.

The combination of modular tangible interfaces and constrained optimization control enables users to operate shape-changing robots by matching their morphology and ensuring safety, allowing adaptation to different environments and application areas.

In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.

The authors in this work identify an in vivo CNS active bifunctional degrader of GSK3. This was discovered via development of orthogonally reactive linker chemistry and a direct-to-biology screen that was able to provide hits of in vivo chemical probe quality.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

While the connectivity of VTA dopamine neurons is well studied, less is known about the connectivity of VTA glutamate and GABA neurons. Here, authors show that these neurons form local circuits to modulate reward, aversion, feeding and locomotion.

Environmental justice and drinking water in the US: Higher proportions of Hispanic/Latino, American Indian/Alaskan Native, and non-Hispanic Black residents were associated with higher public water arsenic and uranium at the county-level, findings differed by region.

It is important to know how the recent COVID-19 pandemic shaped the immune memory against the causal SARS-CoV-2 virus. Here authors show that long years following mild disease at primary infection, SARSCoV-2 spike-specific CD4 + T cells with distinct phenotypes and T cell receptor clonotypes, associated with viral suppression persist.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Endosomal sequestration of lipid-based nanoparticles is a barrier to delivery of nucleic acids. Here the authors test an array of cholesterol variants and perform in-depth investigation of nanoparticle shape, internal structure and intracellular trafficking.

The researchers showcase a microwave-integrated circuit, operating across 1.5–3.0 GHz at micro-Watt power levels, that can perform universal unitary matrix transformations.

The authors study a disordered β-Ta film, finding that quasiparticle recombination is governed by the phonon scattering time, which is faster than conventional recombination in ordered superconductors. The authors interpret the results in terms of quasiparticle localization, which helps to understand the quasiparticle relaxation in disordered superconducting circuits.

Lung cancer screening effectiveness can be subject to variation based on personal risk factors. Here the authors report that heterogeneity in lung cancer screening effectiveness is primarily driven by histology.

Pattern recognition receptors (PRR) critically modulate innate immunity. Here the authors show in cancer cells that interferon responses and anti-tumor immunity activated by dsRNA-induced PRR signaling is enhanced by palbociclib-induced ER stress, with epigenetic changes and altered antigen presentation potentially contributing to this effect.

Oncolytic virus holds potential as a cancer therapy, but further optimization is desirable. Here the authors screen existing drug to find talazoparib, a PARP inhibitor, synergizing with reovirus type 3 Dearing (RT3D) to induce cancer cell apoptosis, anti-tumor immunity, as well as control of primary and rechallenge tumor in mouse models.

This study explores the relationship between telomere length and clonal hematopoiesis. Splicing factor and PPM1D gene mutations are more frequent in people with genetically predicted shorter telomere lengths, suggesting that these mutations protect against the consequences of telomere attrition.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

In clinical and population-based cohorts, a strong contribution of polygenic risk for type 2 diabetes (T2D) significantly modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY). This polygenic T2D burden may also account for MODY-like individuals without identified monogenic causes.

In this study, the authors combine interpolation techniques and deep learning methods, introducing Interpolating Neural Networks (INNs) to model complex systems with high accuracy and low computational cost.

Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

Aggregates of misfolded proteins are sequestered in the aggresome via dynein transport in an aggregate size-dependent manner. Here, authors find episodic transport kinetics mediated by aggresome-dynein adapters are central to this size-filter effect.

This multiomic study, including single-nucleus DNA methylation and chromatin conformation matched with single-nuclei RNA sequencing, provides insights into the epigenomic landscape of human subcutaneous adipose tissue.

Structural analyses of antibody-virus complexes offer critical insights into immune recognition mechanisms. In this report, we present how a patient-derived IgG recognizes a quaternary epitope on EEEV particles through strictly bivalent interactions.

Efficient electro-optic conversion is central to photonic computing, and thin-film lithium niobate (TFLN) offers this capability. Here, the authors demonstrate computing circuits on the TFLN platform, enabling the next generation of photonic computing systems featuring both high-speed and low-power.

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

The broad activity windows of current base editors pose a major challenge to their therapeutic application. Here, the authors established a generalizable re-engineering framework to narrow the activity windows of diverse base editors, streamlining the development of therapeutic base editing.

Acinetobacter baumannii is a multi-drug-resistant pathogen of urgent international concern. Here, the authors develop a protein subunit vaccine which prevents A. baumannii catheter-associated urinary tract infections in mice by inhibiting Abp2D, a key adhesive virulence factor.

The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

tRNA modifications are essential for function, yet their timing relative to processing is unclear. Here, the authors show that queuosine and derivative modifications occur before splicing of pre-tRNA^Tyr, with cryo-EM confirming direct recognition by the QTRT1/2 complex.

How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.

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.

This study used multiplex serology to monitor multiple diseases simultaneously from a single serosurvey. Seroprevalence estimates were performed for five disease categories in Zambezia Province, Mozambique.

The authors demonstrate strain-induced morphotropic phase boundary-like nanodomains in lead-free NaNbO₃ thin films, enabling multi-state switching and large enhancements in dielectric susceptibility and tunability over a broad frequency range.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.