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Graph neural networks built on physically motivated representations enable gradient-based optimization of complex upconverting nanoparticle heterostructures, revealing photophysical design rules and a roadmap for deep learning in nanoscience.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

The synthesis of unprotected C-heteroaryl glycosides is challenging because of the lack of methods to utilize native saccharides as substrates. Now these compounds, capped as redox-active glycosyl sulfide donors, undergo C–C coupling with N-heteroarenes through a photoinduced, thiyl radical-mediated reaction with control over the chemo-, site- and stereoselectivity.

Human impacts on marine ecosystems are increasing the likelihood of pathogenic outbreaks, harmful algal blooms and coral stress. Here the authors develop a CRISPR biomonitoring tool that can help detect key marine species that are important to public health, the aquaculture sector and marine ecosystems.

Modulation of random heteropolymers results in globular polymer clusters with catalytic activity mimicking proteins.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

An aryne precursor is designed to overcome the lack of widespread adoption of arynes due to the undesirable means to generate them and harness their synthetic potential that rivals most functional groups.

A low-cost robotic platform using mainly optical detection to quantify yields of products and by-products allows the analysis of multidimensional chemical reaction hyperspaces and networks much faster than is possible by human chemists.

Engineered carbon nanotube sensors enable the detection of intracranial tumours in blood, identify low-abundance biomarkers and amplify cancer detection by capturing secreted factors from the entire tumour ecosystem for early-stage disease diagnosis.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

The ability to discover and optimise the synthesis of inorganic nanomaterials has significant impact on various fields, from sensing to medicine. Here, the authors use a genetic algorithm to drive a robotic platform toward a pre-defined, spectroscopic goal in order to discover and optimise the conditions for several nanoparticle shapes.

Ultrathin alumina encapsulation protects the magnetic, magnonic, and optical properties of air-sensitive V[TCNE]ₓ, enabling characterization of intrinsic material properties and integration of this organic-based magnet into cryogenic quantum devices.

SmartEM is a ‘smart’ pipeline for electron microscopy-based data acquisition for connectomics. In order to efficiently image large datasets, the approach involves imaging at short pixel dwell times and identifying problematic regions that are then imaged with longer dwell times and therefore higher quality.

A growth-coupled biosynthetic pathway enables xathommatin synthesis in the soil bacterium Pseudomonas putida.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.

Current CO₂ capture strategies often suffer from high thermal regeneration costs. Now a photobase has been shown to reversibly capture and release CO₂ from ambient air using visible light, offering a sustainable, energy-efficient alternative.

Genetically encoded sensors are generally optimized to function during exponential growth rather than stationary phase, which limits their potential value for metabolic engineering and bioproduction. Here, authors engineer a stationary phase green light sensor and use pulsatile light to optimize production of industrially relevant small molecules.

The developmental dynamics of distinct cell types across brain regions remain poorly understood. Here authors generate DevAtlas, a high-resolution developmental 3D atlas, mapping region and cell type-specific growth in GABAergic cells and microglia in early postnatal mouse brains.

Interferometric imaging based on phase-sensitive OCT in living rat eyes demonstrates electromechanical deformation of the rod outer segment associated with reversible isomerization of rhodopsin, providing a new assay for studying visual transduction.

This study quantifies the social costs of aviation’s CO₂ emissions and contrail cirrus. Targeting flights with high contrail cirrus impacts could substantially reduce aviation’s climate damages.

Top-down control is important for sensory processing. In this study, the authors used virus-assisted circuit mapping to identify the brain networks for top-down modulation of multiple sensory modalities and the subnetworks within the visual network, thus providing an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.

Local anesthetic sustained release systems suffer from untriggered rapid drug release upon application. Here the authors overcome this issue by covalently linking tetracaine to a polymer gel via a photo-cleavable linkage, enabling light-triggered and repeatable drug release.

Here, the authors find that relative abundances of stress-sensitive gastrointestinal microbes at age 2 years predicts internalizing symptoms in middle childhood through altered emotion-related brain network connectivity.

Controlling the stereoselectivity of radical reactions remains a major challenge due to the high reactivity of free radicals. Now it has been shown that asymmetric geminate recasting—a catalytic process in which radicals recombine after bond cleavage—can be used to produce chiral sulfur centres through photocatalytic deracemization of sulfinamides.

Calcium imaging of taste neurons and the ventral brain provides insight into evolutionary divergence of food choice in Drosophila species, supporting a role of sensorimotor processing in addition to peripheral receptor changes.

Reduction of gaseous Hg(II) compounds drives atmospheric mercury wet and dry deposition to Earth surface ecosystems. Global Hg models assume this reduction takes place in clouds. Here the authors report a new gas-phase Hg photochemical mechanism that changes atmospheric mercury lifetime and its deposition to the surface.

Injectable bioelectronics face low conductivity due to poor polymer dispersibility. Here, authors engineer dopants in conductive polymers to boost their water dispersibility 5-fold and conductivity 20-fold, enabling biodegradable, 3D-printable hydrogels for wearables and implantable devices.

Parallelized single-molecule fluorescence and single-molecule FRET experiments enable quantitative biophysics investigations of molecular function from multiple samples in a single experiment.

Understanding excited carrier dynamics in semiconductors is central to the continued development of optoelectronic devices. Using extreme ultraviolet transient absorption spectroscopy, Zürchet al. directly and simultaneously observe ultrafast electron and hole dynamics in germanium thin films.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Representing the first successful rational reprogramming of function in a de novo protein, the reactivity of a designed di-iron carboxylate protein from the Due Ferri family was altered from hydroquinone oxidation to arylamine N-hydroxylation through the introduction of a critical third histidine ligand in the active site.

Nitrate, a common pollutant in wastewater and groundwater, has been efficiently converted into valuable ammonia products via an electrochemical method using Ru-dispersed Cu nanowire as the catalyst.

A haem–carbenoid has been proposed to be involved in abiological enzymatic reactions. Now, Hilvert and co-workers provide crystallographic evidence for a haem–carbenoid intermediate as the reactive species in an olefin cyclopropanation reaction catalysed by an artificial metalloenzyme.

The SPECULOOS project detected an Earth-sized planet in a short orbit around a nearby Jupiter-sized star. This planet, SPECULOOS-3 b, is one of the most promising rocky exoplanets for detailed emission spectroscopy characterization with JWST.

Here the authors show that rehabilitating nuclear speckles, membraneless organelles involved in mRNA processing and gene regulation, can boost protein quality control and reduce toxic protein buildup, as well as ameliorate models of diseases like tauopathy and retinal degeneration.

Chemical energy conversion and storage rely on the selective movement of protons and electrons, thus understanding these processes is important for applications. Now experiments at elevated pressures are shown to identify excited-state proton-coupled electron transfer mechanisms and to facilitate merging proton transfer with subsequent electron transfer steps towards a concerted pathway.

The application of photoswitches as light-responsive triggers for phase transitions of porous materials remains poorly explored. Here, the authors report a light-responsive flexible metal-organic framework which undergoes pore contraction upon combined application of light irradiation and adsorption stress via a buckling process of the framework-embedded azobenzene photoswitch.

Molecular catalysts for artificial photosynthesis can break down during operation and stop working, whereas biological photosynthesis uses an enzymatic repair strategy to maintain function. Now, the degradation pathway of a hydrogen-evolving RuPt photocatalyst has been identified, enabling the development of an active repair strategy involving the use of ¹O₂ to reoxidize the deactivated bridging ligand.

Terminal bd oxidases endow bacterial pathogens with resistance to cellular stressors. The authors report the structure of E. coli bd-II type oxidase with the bound inhibitor aurachin D, providing a structural basis for the design of specifically binding antibiotics.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Mixtures of various size fullerenes are available as a component of fullerene soot, but isolating pure fullerenes is a challenging task. Here, the authors use a porphyrin-based supramolecular cage that encapsulates fullerenes with high selectivity and releases C₆₀by a simple washing technique.

Efficient sunlight-to-fuel conversion requires materials that produce long-lived charges, but increasing carrier lifetimes in visible-light-active photocatalysts has proven difficult. Now it has been shown that rapid charge deactivation via metal-centred states prevents long lifetimes and limits photocatalytic performance. These insights bridge solid-state and molecular photochemistry, informing strategies for improved photocatalyst design.

This study reports on an industrial-grade, large-scale, all-in-one integrated and automated laboratory (iAutoEvoLab), combined with a genetic circuit-controlled, growth-coupled continuous evolution system based on OrthoRep, which can evolve proteins with diverse and complex functionalities. These include protein–protein interactions, protein–DNA interactions, proteins requiring both protein–DNA and protein–ligand interactions, and fusion proteins with low to near-zero activities.

Here Zhang et al. establish multiscale relationships that link postmortem cell-type distributions with the in vivo functional organization of the human cerebral cortex, as assessed through functional magnetic resonance imaging.