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Elevated extrinsic tissue-scale forces can drive pathological foreign-body responses to implants, mediated by the Rac2-mediated activation of a subpopulation of mechanoresponsive myeloid cells.

Filamentous fungi are a valuable source of natural therapeutic products such as antibiotics. Here the authors engineer monocellularS. cerevisiaeto perform complex secondary metabolism typical of multicellular fungi in order to demonstrate biosynthesis and secretion of bioactive penicillin.

In this work, authors present an automated, high-throughput platform that utilizes robotics and computer vision to enable creation of a therapeutic phage cocktail, LBP-EC01, effective against over 96% of tested Escherichia coli isolates from urinary tract infections.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Eight decades of forest plot monitoring show a pervasive increase in tree mortality across Australia’s forest biomes driven by climate change, jeopardizing their role as enduring carbon sinks.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

Chemotherapy induces bone loss that compromises skeletal health in cancer patients. Here, the authors show that chemotherapy-induced senescence in bone marrow adipo-lineage cells leads to bone loss and demonstrate that senolytic targeting of senescent cells preserves skeletal health during chemotherapy, providing a potential strategy to protect the skeleton in cancer therapy.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Integrated multi-omics analysis uncovers the role of the vascular disease-associated gene PHACTR1 in regulating mitochondrial dynamics, iron metabolism, and cell cycle.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

A generative artificial intelligence-powered method enables de novo design of highly active enzymes based on information about the geometry of residues in the active site, without requiring protein backbone or sequence information.

The effects of current protected areas on freshwater biodiversity are poorly understood. Here, the authors show that European protected areas have overall limited influence on changes in river biodiversity, underscoring the urgent need for improved effectiveness.

The composition of extracellular vesicles (EVs) is central to their function, yet the field lacks systematic characterization. Here Rai et al. perform proteomic and lipidomic analyses of circulating human plasma EVs and create a web tool for data exploration.

The neurophysiology of excessive daytime sleepiness in Parkinson’s disease (PD) remains unclear. Here, the authors found that beta oscillatory activity, a pathophysiological signature of PD motor signs, is also associated with daytime vigilance in parkinsonism

Zuhra and Petrosino et al. report evidence that cyanide acts as a regulatory gasotransmitter in mammalian cells, where it is shown to affect cellular bioenergetics, most likely via protein S-cyanylation.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

A deep-learning-based de novo design strategy was developed that enables simultaneous scaffolding of three distinct epitopes derived from respiratory syncytial virus within small single-domain immunogens. Crystallographic analyses confirmed precise presentation of the designed motifs. The multiepitope constructs elicited enhanced cross-reactive and neutralizing antibody responses, demonstrating the potential of generative models for complex multisite protein engineering.

C-terminal α-amidated peptides are attractive therapeutic targets, but preparative methods to access amidated pharmaceuticals are limited both on lab and manufacturing-scale. Here, the authors report a straightforward and scalable approach to the C-terminal α-amidation of peptides and proteins from cysteine-extended polypeptide precursors.

Donor spin impurities in silicon are promising qubit candidates, but efficient control and coupling of distant spins remains a key challenge. In this work, the authors experimentally demonstrate coherent coupling between a superconducting flux qubit and individual bismuth donor spins in silicon.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Metabolic labeling experiments on fermenting yeast revealed that ethanol is oxidized to acetaldehyde and acetyl-CoA and is also a major source of NADH and NADPH, demonstrating that ethanol can be consumed as a TCA cycle and redox fuel.

Eggplants are important vegetables worldwide. Here, the authors report 40 genome assemblies of Solanum melongena, its progenitor S. insanum and the allied species S. incanum to construct two pangenomes, and identify loci associated with multiple traits via pangenome-wide association analysis.

RFdiffusion2, an extension of the RFdiffusion framework, builds de novo enzyme active sites using atom-level functional group constraints.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

The enteric nervous system integrates microbial cues to regulate gut function. Using an optogenetic gut culture model, authors show lineage- and frequency-specific neuronal control of immune responses and barrier integrity, shaped by gut microbes.

Targeting IL13Ra2-expressing diffuse midline glioma with specific immunotoxin therapy attenuates DNA-damage response and dramatically increases radiation mediated cell death, significantly improving survival.

Prediction of protein structures on the scale of genomes remains a challenge. Here the authors introduce a protein structure prediction method that uses deep learning to predict inter-atomic distances, torsion angles and hydrogen bonds, and apply it to predict the structures of 1475 Pfam domains.

Laser performance is constrained by various factors. Here, the authors show theoretically that the linewidth can be reduced below the standard quantum limit by engineering the output coupling of a laser to reduce noise, and discuss the potential practical implementation of this approach.