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Parametric matrix models (PMMs) are a new class of machine learning methods using parametrized matrices to find implicit governing equations describing data. PMMs excel at making accurate predictions for scientific computing applications.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Tergaonkar and colleagues identify a noncanonical interaction between the NF-κB transcription factor family member p52 and the ETS family member ETS1. They find that the p52–ETS1 complex is required for splenic germinal center B cell formation and T cell-dependent antibody responses.

Current digital hardware struggles with high computational demands in applications such as probabilistic AI. Here, authors present a small-scale thermodynamic computer composed of eight RLC circuits, demonstrating Gaussian sampling and matrix inversion, suggesting potential speed and energy efficiency advantages over digital GPUs.

In the HELIOS-B randomized trial in patients with transthyretin amyloid cardiomyopathy, treatment with the RNA interference agent vutrisiran, which targets transthyretin, led to improved echocardiographic measures of cardiac structure and function, as compared to placebo.

As presented at the 2025 World Conference on Lung Cancer, in a multiarm phase 2 trial, perioperative immunotherapy was safe and feasible in patients with resectable diffuse pleural mesothelioma, with exploratory data suggesting that ctDNA kinetics could be informative of tumor regression and post-treatment survival.

Cooled liquids that fail to reach their thermodynamic ground state either form gels or glasses. Their formation is thought to be promoted by stable local atomic structures. The role of these local structures has now been verified in experiments that also show that their structural variety is much larger than expected.

Quantification of climate warming in California using machine learning shows increased daily wildfire growth risk by 25%, with an expected increase of 59% and 172% in 2100, for low- and very-high-emissions scenarios, respectively.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

Confinement is encountered in systems varying from simple liquids to biological cells. Williams et al. introduce an adaptive confinement with an elastic wall composed of colloidal particles, whereby the osmotic pressure of the confined system can be directly obtained from the displacement of the wall.

Monarch Butterflies (Danaus plexippus) use their antennae for orientation during their autumnal migration. Guerra and colleagues differentially disrupt clock gene expression in each antenna and find that the individual outputs are integrated and processed to allow precise control of orientation behaviour.

This analysis of whole-genome sequencing data from 421 multiple myeloma samples elucidates the timing of key genomic events and shows associations between the timing of 1q gain and clinical outcome.

Detection of electric fields, central to chemical and biological processes, has been limited to measurements of current (e.g., electrodes) and secondary reporters (e.g., fluorescent dyes). Here, the authors demonstrate an optical platform capable of imaging electric field dynamics with high spatio-temporal resolution.

Dramatic change to environments and climates across the Pleistocene/Holocene boundary is often cited as driving human subsistence change, but at Kiowa, New Guinea, environments and human lifeways remained consistent, stable isotope analysis reveals.

Solubility prediction is a longstanding challenge in the chemical sciences. Here, authors use deep learning to predict organic solubility and extrapolate to new solutes with accuracy approaching the limit of experimental variability.

There are many proposals for new forms of quantum matter in frustrated magnets but in practice disorder prevents the realisation of theoretically-tractable idealised models. Kimchi et al. show that recently observed scaling behavior common to several disordered quantum magnets can be understood as the emergence of a universal random-singlet regime.

As a result of unsupportive sanitation environments, women may cope by suppressing urges to urinate and defecate or by not eating food and/or drinking water. Among urban women in Uganda and India, nearly all women surveyed reported suppressing urination and defecation urges. Withholding food and water was less common. Perceived privacy, safety and health influenced these coping behaviours.

The physical origin of the electronic properties of diamondoids has been difficult to resolve, even by advanced many-body calculations. Now, Patrick and Giustino have shown that quantum nuclear dynamics of carbon atoms must be taken into consideration when explaining electronic and optical properties.

Treatment selection based on the presence of one or more specific biomarkers has the potential to optimize treatment outcomes; nonetheless, most patients lack a specific biomarker that is predictive of benefit from one or more targeted treatment approaches. In this Review, the authors describe the potential of computational analysis approaches to enable the discovery of more complex predictive biomarkers based on comprehensive analysis of large clinical and preclinical datasets and thus address this unmet need.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

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.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

Autonomous delivery of exogenous cargo into plant tissues is achieved by a nanocarrier system harnessing amino acid transporters, enabling force-free, species-independent uptake and ultra-low dose drought resistance in crops like soybean and maize.

The tumor suppressor RAD51C is mutated in ovarian cancers. Through variant analysis the authors identify a mutation cluster in the RAD51C Walker B region important for the repair of DNA double-strand breaks and replicative damage. By identifying Walker B separation-of-function alleles, they show that these activities can be uncoupled.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

High plating currents are achieved in solid-state batteries without dendrites by densifying Li₆PS₅Cl, with modelling showing how specific microstructural changes increase the critical current density.

Drought is a growing issue in tropical rainforests. Here, the authors revisit a long-term rainfall manipulation experiment in the Amazon to show that tree mortality was followed by community-level adjustments to reduced precipitation.

High-throughput screening and hit optimization have led to the development of a small molecule, CIM-834, that targets the SARS-CoV-2 membrane protein and blocks assembly of the virus.

SPP1+ macrophages and CD8 + exhausted T cells are known to crosstalk. Here, the authors discover that extrahepatic tumors facilitate liver metastasis by promoting the formation of an intermediate macrophage population in the liver that inhibits tumor-reactive CD8+ T cell function.

Sobkowiak et al., present a comprehensive genomic epidemiology of SARS-CoV-2 in Peru from 2020 to 2024, highlighting the emergence and spread of key variants including Lambda and Gamma P.1.12. The work provides valuable insights into regional viral transmission dynamics in a high-burden, middle-income setting, emphasizing the importance of sustained genomic surveillance.

Asthma is characterized by abnormal airway hyperresponsiveness. Here the authors identify BPIFA1 as a factor secreted by airway epithelial cells, and show that it regulates contractility of airway smooth muscle cells by binding to and regulating the Orai1 Ca²⁺channel.

Here the authors show that MRAP2 tunes the melanocortin-4 receptor by boosting its G-protein signaling while limiting β-arrestin2 interaction and destabilizing receptor oligomers, shaping appetite regulation.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Transcription and RNA splicing are tightly coupled in eukaryotic cells. Here, authors report the multivalent interaction between U1 snRNP and the transcription elongation complex which may allow efficient co-transcriptional spliceosome assembly.

Liu et al. examine the role of sustained neural activity in the planning and production of speech sequences, revealing a key role for the middle precentral gyrus.

In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.

Molecules with 4 aryl groups attached to a central carbon atom have proven challenging to synthesize despite their attractiveness for a variety of applications. Here the authors report a Pd-catalysed arylation of di- and triarylmethanes, giving a high-yielding route to an array of tetraarylmethanes.

An analysis of bowel samples from bowhead whales collected yearly from 2004–2022 indicates increasing algal toxin concentrations in Arctic food webs due to warming ocean conditions.

Electrolyte gating enables the accumulation of large carrier densities in two-dimensional electron systems. Here, the authors demonstrate that a few-atom thick layer of hexagonal boron nitride can dramatically improve carrier mobility in an electrolyte-gated system by limiting chemical reactions and disorder.