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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

CARD9 and CARD11 propagate signaling by nucleating Bcl10 polymerization in immune cells and are both held in an autoinhibited state prior to activation. Here, the authors combine structural, biochemical, and cell-based approaches to reveal the structural basis for CARD9/11 autoinhibition and show that the two proteins are activated through similar but distinct mechanisms.

A novel multistep strategy reveals how parent-of-origin effects shape complex traits in large-scale biobanks.

Ulcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Here the authors report that colonoids from children with ulcerative colitis exhibit hypermetabolism and cellular stress primarily driven by lipid dysregulation. Pharmacological inhibition of PPAR-a, a transcriptional regulator of lipid metabolism, alleviates epithelial stress and inflammation.

It is a challenge to scale up laser-ion acceleration to higher ion energies. Here the authors demonstrate a hybrid acceleration scheme based on the relativistic induced transparency mechanism using linearly polarised laser interaction with foil targets and its future implication in using high power lasers.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

Conflicting mechanisms have been proposed to explain the sub-bandgap turn-on behaviour of heterojunction organic light-emitting diodes (OLEDs). Here, by probing and modifying the OLED heterojunction, the authors show that band-to-band recombination is the most likely radiative recombination process.

It has been proposed that phonons propagating through a material can be used for quantum computing, in a similar manner to photons. Now, several of the quantum gates and measurements needed for this approach have been demonstrated.

Impaired Aβ clearance in late-onset Alzheimer’s disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry Aβ in peripheral circulation and CSF in AD, suggesting a role in Aβ clearance.

Merging photoredox and biocatalysis provides opportunities to address challenges in synthetic chemistry. Now the combination of a ruthenium photocatalyst for oxidative radical formation and ‘ene’-reductases for radical interception enables an enantiodivergent decarboxylative alkylation reaction.

G2E3-catalysed H3K14 mono-ubiquitination is crucial for SUV39H compartmentalization and H3K9 trimethylation in pericentromeric heterochromatin, which is essential for proper euchromatin organization and transcriptional regulation in mammalian cells.

Our understanding of the evolutionary sequence of tetrapod characters is hindered by a limited fossil record of primitive finned tetrapods. This study reports a new stem-tetrapod from ~409 million years ago, which displays morphological features shared by tetrapods and lungfishes, and extends the earliest record of tetrapods by ~10 million years.

Literature mining, such as systematic review and meta-analysis, is crucial for discovering, integrating, and interpreting emerging research. This study presents a specialized large language model for literature that outperforms six general LLMs and helps clinicians in study selection and data extraction tasks.

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.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Recent advancements have enabled quantum control and measurement of mechanical resonators. Here the authors demonstrate quantum entanglement between two mechanical resonators on separate substrates by sharing one and two quanta of energy, followed by quantum measurement of these entangled states.

Results from the randomized, noncomparative, phase 2 MATISSE trial show that ultra-short neoadjuvant therapy with ipilimumab and nivolumab can prevent surgery and radiotherapy in patients with resectable cutaneous squamous cell carcinoma, with an early decrease in total lesion glycolysis by [¹⁸F]FDG-PET/CT associated with response.

A highly chemoselective and enantioselective cross-electrophile coupling using ‘ene’-reductases is reported, and photoexcited enzymes demonstrate the ability to carry out reactions between electrophiles that are not known for small-molecule catalysis.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Unprecedented groundwater recovery ( ~ 0.7 m/yr) driven by water diversions, strict pumping regulations, and a wet climate occurred in the North China Plain after decades of depletion, showing large-scale recovery is possible under human intervention.

Lipid II embodies the bricks used to build the essential bacterial cell wall component peptidoglycan. A facile new procedure for preparation of species-specific Lipid II in high yields can now be used to unlock the door to antibiotic discovery.

Electrified thermal energy storage converts electricity into heat for thermal energy use. This Review assesses available and emerging technologies, identifying research needs for scalable, long-duration and efficient deployment.

Assemblies of six representative perennial Glycine genomes and a comparison with annual soybean genomes reveal evolutionary patterns, differentiation and adaptation of annual and perennial genomes and mechanisms driving subgenome fractionation.

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.

Enantioselective catalytic C(sp³)–H fluorination has been limited to electrophilic fluorine sources. Now chiral palladium catalysts bearing amino sulfonamide ligands enable enantioselective incorporation of nucleophilic fluoride into unactivated aliphatic C–H bonds with demonstrated applications to ¹⁸F-radiolabelling using [¹⁸F]KF.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

Unlike the other plant pathogens, Phytophtora infestans, the causative pathogen of potato late blight, can hardly take up dsRNA, which is a key obstacle in using dsRNA for disease control. Here, the authors design a self-assembled multicomponent nano-bioprotectant for potato late blight management.

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.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Disadvantaged communities in the U.S. have far fewer public EV chargers and face more reliability issues. This study highlights critical equity gaps and the need for targeted investments in EV infrastructure to support a just, clean energy transition.

Cholinergic interneurons act at nicotinic receptors to depress dopamine release, interrupting its relationship to dopamine neuron firing and supporting an inverse scaling of dopamine release according to cholinergic activity.

Sheng et al. characterize features associated with neuroinflammation-related genes and cognitive resilience using a neuroimaging biomarker. The pathological effect of the MST1 gene on cognitive resilience is mediated by the mismatch between metabolic fluctuation coupling in the limbic orbital frontal cortex and amyloid protein deposition.

Genetic studies of Chinese individuals have been performed, but mostly with short read sequencing, limiting the types of variants that can be identified. Here, the authors perform long read sequencing of 945 han Chinese individuals, finding structural variants under natural selection and those associated with human traits and evolutionary history.

Intermetallics are traditionally characterised by their inherent brittleness due to a lack of sufficient slip systems and the absence of strain hardening. Here authors show that a single-phase distorted high entropy B2 intermetallic alloy displays notable strength and plasticity at room temperature, along with stable plastic flow at high homologous temperatures.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Membrane proteins are essential for any cell but difficult to fold. Here, the authors show that the EMC acts as a chaperone for membrane proteins. They dissect client recognition and provide a molecular mechanism that underlies this EMC function.

Input–output models can predict multiregional brain network dynamics in response to temporally varying patterns of ongoing direct electrical stimulation, with variabilities in prediction accuracy explained by at-rest functional connectivity.

Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Cerebral palsy (CP) is a heterogeneous disorder that has been historically attributed to environmental factors with genetic contributions being discovered more recently. Here the authors perform microarray-based analysis of copy number variations in a cohort of children with CP and their parents and find chromosomal abnormalities linked to the disease.

The study assembled a chromosome-level genome of Cycas panzhihuaensis, the last major lineage of seed plants for which a high-quality genome assembly was lacking. The study closes an important gap in our understanding of genome structure and evolution in seed plants.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

The soils of urban greenspaces are strikingly rich. This study finds that the variety of microbial life there is linked to acidic conditions and that this diversity is more homogenous than found in farmland soils.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.