Search

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

An integrated structural biology approach combining NMR, cryo-EM, X-ray crystallography and molecular dynamics simulations is implemented to characterise the conformational dynamics and interactions of the eukaryotic RNA exosome complex.

The authors showcase the capabilities of time-resolved momentum microscopy to image spin- and valley-resolved excitons in monolayer WS₂ with high energy resolution, revealing distinct long-lived, valley-polarized dark excitons that dominate at different timescales.

The authors show that the m⁶A reader protein YTHDF2 negatively regulates Th9 cell differentiation and function. Ablation of YTHDF2 promotes antigen-specific Th9 cell and CAR-Th9 cell antitumor activity in solid tumors.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

Malaria control and elimination require environmentally safe strategies. Here, the authors propose L-DOPA, a naturally occurring tyrosine derivative, as a mosquito dietary intervention that can shorten lifespan and reduce malaria parasite burden of female Anopheles gambiae mosquitoes.

The Perseverance rover detected polycyclic aromatic hydrocarbons preserved within sulfates in the fan and floor of Jezero crater on Mars, offering new insights into past habitability and the preservation of organic matter on Mars.

In Drosophila, the physical structure of the eye has a key role in the directional tuning of motion-sensitive neurons, showing how navigational behaviour is tightly associated with anatomy.

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.

The authors use 1,603 estimates of local extinctions from 1980 to 2021 to show that dragonfly species with wing ornamentation have disproportionately gone extinct and lost habitat because of climate change and wildfire. This highlights the important role of mating traits in species survival under change.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Electron hopping in geometrically frustrated lattices can result in a rich variety of unusual behaviours. Now, the orbital arrangement in a van der Waals metal with a non-frustrated, primitive lattice is found to show similar effects.

A model developed with data from 19,403 patients with colorectal cancer for prediction of 1-year mortality is used as a decision support tool in a prospective cohort, showing promising results in reducing postoperative complications.

Friction consolidation transforms brittle Sm–Co powders into dense magnets via shear-driven redox reactions and localized heating, enabling phase-selective refinement and enhanced magnetization in a single-step, low-temperature process.

Asymmetrical distribution of tau pathology in Alzheimer’s disease is linked to asymmetrical amyloid-beta deposition, not reduced brain connectivity, suggesting regional vulnerability plays a key role in determining the distribution of tau pathology.

In vivo chimeric antigen receptor (CAR)-T cell engineering uses targeted delivery systems to generate CAR-T cells directly in patients, bypassing ex vivo manufacturing. This Review examines emerging viral and lipid nanoparticle platforms, early clinical proof of concept and potential applications beyond cancer.

A picometer-scale optical ruler is proposed based on precise location of a vanishingly small transverse optical phase singularity. This ruler is capable of measuring three-dimensional picometric displacements within optical interferometric systems.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

US healthcare contributes 8.5% of national greenhouse gas emissions, but its policies to guide mitigation and waste reduction are underdeveloped. We recommend national policies to streamline the adoption of best practices, address implementation challenges to achieve net-zero goals and serve as useful exemplars for other nations.

Elucidating the nature of the metallocofactors in nitrogenase enzymes, and preparing synthetic analogues of these clusters, is a classic target for bioinorganic chemists. Now the transformation of [Fe₂S₂]²⁺ rhombs to [Fe₈S₈]ⁿ⁺ clusters has been achieved through a series of redox- and ligand-substitution reactions.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

Biological nitrogen fixation may impose stronger constraints on the carbon sink in natural terrestrial biomes and represent a larger source of agricultural nitrogen than is generally considered in analyses of the global nitrogen cycle.

Self-assembled multidomain supramolecular peptide hydrogels that engage in dynamic covalent bonding with small-molecule drugs and biologics are shown to offer sustained release, extend the activity, and maintain safe and potent drug levels in vivo.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

The emissions of leading fossil-fuel and cement producers have been systematically linked to particular heatwaves. Three scientists discuss the methodology behind the result and its potential impact on climate-liability court cases.

Sperm–egg adhesion is crucial for mammalian reproduction. Here, authors report the human Izumo1:Juno complex, a key regulator of sperm-egg adhesion, forms an unusually strong bond through a secondary binding site, which is impaired in an infertility-associated Juno mutant.

Phonons are quanta of the vibrations of the lattice in solids. They can carry angular momentum and allow an emergent chirality. This Perspective defines various types of chiral phonon and classifies the previously observed manifestations of them.

Despite exhibiting ferroelectric features, SrTiO₃ fails to display long-range polar order at low temperatures due to quantum fluctuations. An ultrafast X-ray diffraction experiment now probes polar dynamics of this material at the nanometre scale.

Locked nucleic acids have high binding and utility but currently suffer from off target effects due to the high does needed. Here, the authors show lipid nanoparticles can safely and effectively deliver locked nucleic acids to inflamed tissue in the gut, reducing the required dose and improving therapeutic outcomes in IBD.

PROTAC development has surged in popularity, however our ability to characterize PROTAC specificity in living cells has lagged behind. Here, the authors develop ProtacID, a flexible proximity-dependent biotinylation (BioID)-based approach to identify PROTAC-protein interactions in living cells.

This Perspective from Summerfield et al. considers the impacts of advanced artificial intelligence systems on the process and function of democracy. The authors explore a wide range of potential risks and opportunities.

Wildfire risk in California’s WUI is rising. Analysis of past events shows home hardening and defensible space can reduce structure loss by up to 52%, but coordinated, community-scale action is essential to maximize impact.

Rare earth mineralisation at Maoniuping formed when its carrying carbonatite brine-melt reacted with surrounding siliceous rocks, forming an antiskarn. The melt lost its fluxing alkali elements, which led to deposition of coarse grained bastnäsite.

Determining dynamics of Fe–CO bond breaking in heme proteins is essential to understand the interplay between protein function and dynamics. Here, the authors report the first experimental proof for the two-step CO photodissociation, involving the previously unknown slower ~15 ps process.

A streak camera for characterizing the ultrashort X-ray pulses produced by a free-electron laser is reported. The scheme has a single-shot capability, a resolution of a few femtoseconds and is expected to become a useful tool for X-ray metrology, including experiments involving time-resolved spectroscopy and imaging.

Cocaine chemogenetics in rats is a selective approach for countering drug reinforcement by clamping dopamine release in the presence of cocaine.

Cangkrama et al. show that tumor cells from various cancer types use the mitochondrial trafficking protein MIRO2 and nanotubes to transfer mitochondria into surrounding fibroblasts, thereby inducing cancer-associated fibroblast differentiation and subsequent tumor growth.

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.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

JWST has detected \({{\rm{H}}}_{3}^{+}\) and auroral emissions at Neptune—the only giant planet in the Solar System for which they had proved to be elusive up to now. The observations reveal a factor-of-two cooling of Neptune’s upper atmosphere compared with Voyager 2 data, indicative of energy balance processes acting on a shorter timescale than solar forcing.