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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Disparities in risk and outcomes of pediatric acute lymphoblastic leukemia (ALL) are apparent between different ancestries. Here the authors identify genetic variants with African ancestry-specific risks for developing pediatric B-cell ALL that are also linked to greater 5-year mortality risk.

Black carbon produced by the burning of biomass and fuels is the most stable carbon compound in nature, yet its path from land to the deep ocean where it persists for thousands of years remains mysterious. Here Coppola and colleagues characterize the black carbon exported by the Amazon River, the largest river in the world.

This Review compares predictive genomics across humans, animals and plants, and outlines shared statistical foundations and key differences in phenotype structure, as well as opportunities for biologically grounded, generalizable artificial intelligence models.

Electrotherapy requires electronic powered devices, set-up, and accessories. Here the authors, developed an integrated single-use platform for wearable electrotherapy as simple as a band-aid

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

HTLV-1 type-C causes more severe disease than type-A, but the underlying reason is unclear. Here the authors show in a macaque model how type-C orf-I affects lung pathogenesis and the immune response to HTLV-1, providing a model to test viral targets for disease prevention.

Viruses generally have compact genomes, resulting in many viral mRNAs with short 5’ untranslated regions. An antiviral complex exploits this feature of viral mRNAs to selectively inhibit viral protein synthesis and repress viral replication.

Here, a combination of forward genetics and genome-wide association analyses has been used to show that variation at a single genetic locus in Arabidopsis thaliana underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains the allele's persistence in natural populations throughout the world, even though it drastically reduces the production of new leaves.

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.

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.

Covalent KRAS inhibitors show initial responses but resistance limits durability. Here drug-induced hapten peptides are identified and characterized, enabling production of high affinity, cross-HLA T cell engagers that stabilize low density hapten peptide MHCs to drive tumor-specific killing.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Diffusion models are reframed by developing a generative blood cell classifier that performs reliably in low-data regimes, adapts to domain shifts, detects anomalies with robustness and provides uncertainty estimates that surpass clinical expert benchmarks.

Synthetic microbial consortia are collections of strains which can segregate metabolic tasks for efficient use in biomaterials, biomanufacturing, and biotherapeutics. Here, the authors present a method to maintain and tune the ratio of two co-cultured bacterial strains via growth medium manipulation.

Authors measure plasma proteins in a cohort of hospitalised patients presenting to the emergency department with suspected infection, revealing six discrete host response clusters that were driven by pathogen exposure and organ dysfunction, and had distinct clinical characteristics, hospital courses, and responses to treatment.

An optimal model-experiment integration for testing many complex hypotheses is still lacking. Here authors introduce improv, a modular software platform enabling real-time adaptive neuroscience experiments, orchestrating parallel data collection, modeling, and experimental control. Authors demonstrate various use cases, including online neural analysis and closed-loop optogenetics in zebrafish.

The XPD/Rad3 helicase, YoaA-χ, helps resolve DNA damage in E. coli. Here, the authors show that single-stranded DNA binding protein (SSB) affects helicase activity in a substrate specific manner. Single molecule experiments show YoaA- χ can pull SSB along DNA while translocating

This study shows that non-invasive ultrasound to the human nucleus accumbens can modulate deep brain activity and enhance reward-guided learning, offering a potential alternative to invasive neuromodulation therapies.

Analysis of a large galaxy sample shows that black hole activity is greater in galaxies in which the stellar and gas kinematics are misaligned. This observation suggests that the misalignment, driven by external gas accretion, fuels the central supermassive black holes.

A machine-learning-based computational approach to probe pathway coessentiality reveals that complex II of the electron transport chain regulates de novo purine synthesis, and can be targeted to treat acute myeloid leukaemia.

The Neolithic Revolution marked an important shift from foraging to farming in human society. Here, the authors show that in Europe the spread of farming involved mostly within-group mating and limited cultural transmission.

Scaling Si spin qubits relies on the uniform control of qubit-host interactions. This work finds correlations in qubit energy levels across a manufactured device arising from placement of Ge in the quantum well, consistent with atomistic modeling.

Inversion of C3 stereochemistry of monoterpenoid indole alkaloids (MIAs) has to occur at some point during their biosynthesis; however, the mechanism has remained unresolved. Here, the authors report an oxidase–reductase enzyme pair encoded within a gene cluster and demonstrate their collaborative role in inverting MIA C3 stereochemistry.

A key component of quantum error correction is the decoding algorithm, which needs to be accurate but also with a computational overhead that doesn’t lead to backlogs and allows fast logical clock rates. Here, the authors show an FPGA-driven decoder featuring a coarse-grained parallel architecture and on-the-fly error model updates, allowing both high accuracy and real-time operation.

Quantifying genomic aberrations resulting from designer nucleases activity is essential for gene therapy clinical translation. Here, the authors present a modular digital PCR technique that profiles DNA repair precision and cut-repair cycles at the edited loci, exposing current evaluation biases.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Parallel operation of two exchange-only qubits consisting of six quantum dots arranged linearly is shown to be achievable and maintains qubit control quality compared with sequential operation, with potential for use in scaled quantum computing.

Phosphorus locked in ancient marine carbonates shows that ocean phosphorus rose and fell with atmospheric oxygen during the Great Oxidation Event, Earth’s first major oxygenation. Models suggest brief nutrient pulses could have accelerated oxygen production

Hot carriers in perovskites experience slow cooling.

vConTACT3 enables multirank, large-scale classification of eukaryotic and prokaryotic viruses.

The potential roles of viruses in microbial-induced permafrost thaw, which is accelerated by climate change, are unclear. Here, Trubl et al. sample a permafrost thaw gradient and identify thousands of new viruses carrying genes with metabolic-related functions, which might influence the fate of stored carbon.

Topological phases are unusual states of matter whose properties are robust against small perturbations. Using a photonic quantum walk system, Kitagawaet al. simulate one-dimensional topological phases and reveal novel topological phenomena far from the static or adiabatic regimes.

Using data from 142,238 Mass General Brigham Biobank participants, researchers explored population history and social and genetic risk factors for disease in Greater Boston. The study links genetics and context to guide equitable precision health.

Cells can regulate their mass density. Here, the authors demonstrate how eukaryotes establish and maintain a lower density in the nucleus than in the cytoplasm via pressure balance, and how deviations emerge during pathophysiological states like senescence.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

Opposing forces generated by exopolysaccharide trail binding versus type IV pilus retraction generate a high cyclic diGMP–high cyclic AMP state in Pseudomonas aeruginosa that promotes social motility.

DynamicAtlas integrates fixed and live imaging data to generate a morphodynamic atlas of Drosophila development.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Particle fusion is a promising process for constructing nanomaterials, but challenging to control in synthetic systems. Here, the authors report a method for kinetically regulated particle fusion controlled by variation in polymer chain length.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Barcoding microbial ribosomal RNA creates a recording of gene transfer events without requiring translation.

The precision of determining the phase of an optical atomic clock is increased above the standard quantum limit in a new spectroscopic method.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

Allogenic mesenchymal stem cells are engineered with three mRNAs to bind to multiple myeloma B cells while activating T cells for cancer therapy.

Through direct visualization of how the moiré potential enhances and modulates the topological flat band in rhombohedral graphene superlattice, this work provides key insights into the microscopic mechanism of the fractional quantum anomalous Hall effect